Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.

PubMed Central

Wolzt, M; Schmetterer, L; Rheinberger, A; Salomon, A; Unfried, C; Breiteneder, H; Ehringer, H; Eichler, H G; Fercher, A F

1995-01-01

specific approach for the detection of pulse pressure changes. A battery of non-invasive tests appears useful for the characterization of cardiovascular drugs. Gender differences may not pose a relevant problem for the study of acute haemodynamic effects of cardiovascular drugs. Images Figure 1 PMID:7640140

Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain

PubMed Central

Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W

2016-01-01

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit. PMID:27126324

Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain.

PubMed

Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W

2017-05-01

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit.

Pleural effusion decreases left ventricular pre-load and causes haemodynamic compromise: an experimental porcine study.

PubMed

Wemmelund, K B; Lie, R H; Juhl-Olsen, P; Frederiksen, C A; Hermansen, J F; Sloth, E

2012-08-01

Although pleural effusion is a common complication in critically ill patients, detailed knowledge is missing about the haemodynamic impact and the underlining mechanisms. The aim of this study was to evaluate the haemodynamic effect of incremental pleural effusion by means of invasive haemodynamic parameters and transthoracic echocardiography. This experimental interventional study was conducted using 22 female piglets (17.5-21.5 kg) randomized for right-side (n = 9) and left-side (n = 9) pleural effusion, or sham operation (n = 4). Pleural effusion was induced by infusing incremental volumes of saline into the pleural cavity. Invasive haemodynamic measurements and echocardiographical images were obtained at baseline, a volume of 45 ml/kg, a volume of 75 ml/kg and 45 min after drainage. No difference (all P > 0.147) was found between right- and left-side pleural effusion, and the groups were thus pooled. At 45 ml/kg cardiac output, mean arterial pressure, stroke volume and mixed venous saturation decreased (all P < 0.003); central venous pressure and pulmonary arterial pressure increased (both P > 0.003) at this point. The changes accelerated at 75 ml/kg. At 45 ml/kg left ventricular pre-load in terms of end-diastolic area decreased significantly (P < 0.001). The effect on haemodynamics and cardiac dimensions changed dramatically at 75 ml/kg. Cardiac output, mean arterial pressure, central venous pressure and left ventricular end-diastolic area returned to normal during a recovery period of 45 min (all P > 0.061). Incremental volumes of unilateral pleural effusion induced a significant haemodynamic impact fully reversible after drainage. Pleural effusion causes a significant decrease of left ventricular pre-load in a diverse picture of haemodynamic compromise. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

PubMed

Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

2018-01-01

There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

Shock-like haemodynamic responses induced in the primary visual cortex by moving visual stimuli

PubMed Central

Robinson, P. A.

2016-01-01

It is shown that recently discovered haemodynamic waves can form shock-like fronts when driven by stimuli that excite the cortex in a patch that moves faster than the haemodynamic wave velocity. If stimuli are chosen in order to induce shock-like behaviour, the resulting blood oxygen level-dependent (BOLD) response is enhanced, thereby improving the signal to noise ratio of measurements made with functional magnetic resonance imaging. A spatio-temporal haemodynamic model is extended to calculate the BOLD response and determine the main properties of waves induced by moving stimuli. From this, the optimal conditions for stimulating shock-like responses are determined, and ways of inducing these responses in experiments are demonstrated in a pilot study. PMID:27974572

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults. PMID:20111646

Laser Echosclerotherapy of varicose veins with haemodynamic echo-doppler evaluation : some rationale and short-term outcomes

NASA Astrophysics Data System (ADS)

Vettorello, Gianfranco; Marini, Leonardo

2009-06-01

Purpose: The aim is to verify short-term results in Endovenous Laser Treatment (EVLT) performed in haemodynamic way in patients belonging to C2, C3 classes and type I, II, III venous shunts, according respectively with CEAP and Teupitz classification. Methods: Minor changes of technique were applied to EVLT in order to provide haemodynamic conditions. Treatment efficacy, anatomical failure, complications, recurrence rate and clinical improvements were analyzed. 105 limbs were treated from November 2004 to November 2007. Clinical and Echo-Colour-Doppler (ECD) follow up was performed two weeks, one, two and three years after the surgery. Results: in 79 inferior limbs follow-up was concluded and this are the final data: a) no Deep Venous Thrombosis (DVT) was detected; b) a notable reduction of recurrence if compared with groin recurrence rate in traditional stripping; e) satisfactory cosmetic results and short recovery were found in all the patients. Conclusions: In selected patients haemodynamic-guided EVLT is equally safe and efficient than standard. Clinical and aesthetical outcomes are durable without statistical differences on the plan of disease progression and complications. The recurrence rate is lower in EVLT haemodynamic-guided surgery than in conventional stripping. Long-term outcomes should be investigated. We need studies camparison among the three different kind of surgery performed in haemodynamic way

Bitter tastants alter gastric-phase postprandial haemodynamics.

PubMed

McMullen, Michael K; Whitehouse, Julie M; Whitton, Peter A; Towell, Anthony

2014-07-03

Since Greco-Roman times bitter tastants have been used in Europe to treat digestive disorders, yet no pharmacological mechanism has been identified which can account for this practice. This study investigates whether the bitter tastants, gentian root (Gentian lutea L.) and wormwood herb (Artemisia absinthium L.), stimulate cephalic and/or gut receptors to alter postprandial haemodynamics during the gastric-phase of digestion. Normal participants ingested (1) 100 mL water plus capsules containing either cellulose (placebo-control) or 1000 mg of each tastant (n=14); or (2) 100mL of water flavoured with 500 or 1500 mg of each tastant (a) gentian (n=12) and (b) wormwood (n=12). A single beat-to-beat cardiovascular recording was obtained for the entire session. Pre/post-ingestion contrasts with the control were analysed for (1) the encapsulated tastants, in the "10 to 15" minute post-ingestion period, and (2) the flavoured water in the "5 to 10" minute post-ingestion period. Water, the placebo-control, increased cardiac contraction force and blood pressure notwithstanding heart rate decreases. Encapsulated tastants did not further alter postprandial haemodynamics. In contrast gentian (500 and 1500 mg) and wormwood (1500 mg) flavoured water elicited increased peripheral vascular resistance and decreased cardiac output, primarily by reducing stroke volume rather than heart rate. Drinking 100mL water elicits a pressor effect during the gastric-phase of digestion due to increased cardiac contraction force. The addition of bitter tastants to water elicits an additional and parallel pressor effect due to increased peripheral vascular resistance; yet the extent of the post-prandial blood pressure increases are unchanged, presumably due to baroreflex buffering. The vascular response elicited by bitter tastants can be categorised as a sympathetically-mediated cephalic-phase response. A possible mechanism by which bitter tastants could positively influence digestion is altering

Ultrafast laser ablation for targeted atherosclerotic plaque removal

NASA Astrophysics Data System (ADS)

Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

2015-07-01

Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

Ocular haemodynamic changes after single treatment with photodynamic therapy assessed with non-invasive techniques.

PubMed

Maar, Noemi; Pemp, Berthold; Kircher, Karl; Luksch, Alexandra; Weigert, Günther; Polska, Elzbieta; Tittl, Michael; Stur, Michael; Schmetterer, Leopold

2009-09-01

To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods.

Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability.

PubMed

Xu, Rende; Li, Chenguang; Wu, Yizhe; Shen, Li; Ma, Jianying; Qian, Juying; Ge, Junbo

2017-02-01

Emerging evidence indicates that proinflammatory macrophage polarization imbalance plays a key role in atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in macrophage polarization is unknown. This study investigates the potential role of KCa3.1 in transcriptional regulation in macrophage polarization and its relationship to plaque instability. Human monocytes were differentiated into macrophages using macrophage colony-stimulating factor. Macrophages were then polarized into proinflammatory M1 cells by interferon-γ and lipopolysaccharide and into alternative M2 macrophages by interleukin-4. A model for plaque instability was induced by combined partial ligation of the left renal artery and left common carotid artery in apolipoprotein E knockout mice. Significant upregulation of KCa3.1 expression was observed during the differentiation of human monocytes into macrophages. Blocking KCa3.1 significantly reduced the expression of proinflammatory genes during macrophages polarization. Further mechanistic studies indicated that blocking KCa3.1 inhibited macrophage differentiation toward the M1 phenotype by downregulating signal transducer and activator of transcription-1 phosphorylation. In animal models, KCa3.1 blockade therapy strikingly reduced the incidence of plaque rupture and luminal thrombus in carotid arteries, decreased the expression of markers associated with M1 macrophage polarization, and enhanced the expression of M2 markers within atherosclerotic lesions. These results suggest that blocking KCa3.1 suppresses plaque instability in advanced stages of atherosclerosis by inhibiting macrophage polarization toward an M1 phenotype. © 2016 American Heart Association, Inc.

[Effects of liensinine on haemodynamics in rats and the physiologic properties of isolated rabbit atria].

PubMed

Wang, J L; Nong, Y; Jing, M X

1992-01-01

Liensinine(Lien), an alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, has been shown to have anti-arrhythmic action, its mechanism may be related to blockade of Ca2+, Na+ influx. Lien 3 mg/kg i.v. may temporarily inhibit all parameters of haemodynamics in anesthetized or pithed rats. The inhibitory effects on LVP, +dp/dtmax and SAP in anesthetized rats are slightly stronger than those of quinidine (Qui) 3 mg/kg. Lien 1-30 mg/kg dose-dependently produced these actions. Lien and Qui 12 mg/kg lowered LVP, +dp/dtmax and SAP by 33%, 37%, 29% and 9%, 12%, 9% respectively. While both of them inhibited the other parameters of haemodynamics with nearly equal degrees. The degrees of inhibitory effect of Lien 12 mg/kg on all haemodynamic parameters nearly corresponded to these of verapamil 1 mg/kg. Lien 1-100 mumol/L reduced the contractile force of isolated left atria and the spontaneously beating rate of isolated right atria of rabbits in concentration-dependent manner. These results indicate that the properties of the effect of Lien on haemodynamics may be similar to those of verapamil and different from those of Qui.

[Is regression of atherosclerotic plaque possible?

PubMed

Páramo, José A; Civeira, Fernando

As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Relation between exercise central haemodynamic response and resting cardiac structure and function in young healthy men.

PubMed

Babcock, Matthew C; Lefferts, Wesley K; Heffernan, Kevin S

2017-07-01

Left ventricular (LV) structure and function are predictors of cardiovascular (CV) morbidity and mortality and are related to resting peripheral haemodynamic load in older adults. The central haemodynamic response to exercise may reveal associations with LV structure and function not detected by traditional peripheral (brachial) measures in a younger population. To examine correlations between acute exercise-induced changes in central artery stiffness and wave reflections and measures of resting LV structure and function. Sixteen healthy men (age 26 ± 6 year; BMI 25·3 ± 2·7 kg m -2 ) had measures of central haemodynamic load measured before/after a 30-s Wingate anaerobic test (WAT). Common carotid artery stiffness and reflected wave intensity were assessed via wave intensity analysis as a regional pulse wave velocity (PWV) and negative area (NA), respectively. Resting LV structure (LV mass) and function [midwall fractional shortening (mFS)] were assessed using M-mode echocardiography in the parasternal short-axis view. There was a significant association between mFS and WAT-mediated change in carotid systolic BP (r = -0·57, P = 0·011), logNA (r = -0·58, P = 0·009) and PWV (r = -0·44, P = 0·045). There were no significant associations between resting mFS and changes in brachial systolic BP (r = -0·26, P>0·05). There were no associations between resting LV mass and changes in any haemodynamic variable (P>0·05). Exercise-induced increases in central haemodynamic load reveal associations with lower resting LV function in young healthy men undetected by traditional peripheral haemodynamics. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Haemodynamics of aerobic and resistance blood flow restriction exercise in young and older adults.

PubMed

Staunton, Craig A; May, Anthony K; Brandner, Christopher R; Warmington, Stuart A

2015-11-01

Light-load blood flow restriction exercise (BFRE) may provide a novel training method to limit the effects of age-related muscle atrophy in older adults. Therefore, the purpose of this study was to compare the haemodynamic response to resistance and aerobic BFRE between young adults (YA; n = 11; 22 ± 1 years) and older adults (OA; n = 13; 69 ± 1 years). On two occasions, participants completed BFRE or control exercise (CON). One occasion was leg press (LP; 20 % 1-RM) and the other was treadmill walking (TM; 4 km h(-1)). Haemodynamic responses (HR, Q, SV and BP) were recorded during baseline and exercise. At baseline, YA and OA were different for some haemodynamic parameters (e.g. BP, SV). The relative responses to BFRE were similar between YA and OA. Blood pressures increased more with BFRE, and also for LP over TM. Q increased similarly for BFRE and CON (in both LP and TM), but with elevated HR and reduced SV (TM only). While BFR conferred slightly greater haemodynamic stress than CON, this was lower for walking than leg-press exercise. Given similar response magnitudes between YA and OA, these data support aerobic exercise being a more appropriate BFRE for prescription in older adults that may contribute to limiting the effects of age-related muscle atrophy.

Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously

PubMed Central

Endo, Hidenori; Niizuma, Kuniyasu; Endo, Toshiki; Funamoto, Kenichi; Ohta, Makoto; Tominaga, Teiji

2016-01-01

This was a proof-of-concept computational fluid dynamics (CFD) study designed to identify atherosclerotic changes in intracranial aneurysms. We selected 3 patients with multiple unruptured aneurysms including at least one with atherosclerotic changes and investigated whether an image-based CFD study could provide useful information for discriminating the atherosclerotic aneurysms. Patient-specific geometries were constructed from three-dimensional data obtained using rotational angiography. Transient simulations were conducted under patient-specific inlet flow rates measured by phase-contrast magnetic resonance velocimetry. In the postanalyses, we calculated time-averaged wall shear stress (WSS), oscillatory shear index, and relative residence time (RRT). The volume of blood flow entering aneurysms through the neck and the mean velocity of blood flow inside aneurysms were examined. We applied the age-of-fluid method to quantitatively assess the residence of blood inside aneurysms. Atherosclerotic changes coincided with regions exposed to disturbed blood flow, as indicated by low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The mean velocities of blood inside atherosclerotic aneurysms were lower than those inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older than that in nonatherosclerotic aneurysms, especially near the wall. This proof-of-concept study demonstrated that CFD analysis provided detailed information on the exchange and residence of blood that is useful for the diagnosis of atherosclerotic changes in intracranial aneurysms. PMID:27703491

Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

PubMed Central

Picano, Eugenio; Paterni, Marco

2015-01-01

A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique

Application of infrared fiber optic imaging in atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Guo, Bujin; Casscells, S. W.; Bearman, Gregory H.; McNatt, Janice; Naghevi, Morteza; Malik, Basit A.; Gul, Khawar; Willerson, James T.

1999-07-01

Rupture of atherosclerotic plaques - the main cause of heart attach and stokes - is not predictable. Hence even treadmill stress tests fail to detect many persons at risk. Fatal plaques are found at autopsies to be associated with active inflammatory cells. Classically, inflammation is detected by its swelling, red color, pain and heat. We have found that heat accurately locates the dangerous plaques that are significantly warmer then atherosclerotic plaques without the same inflammation. In order to develop a non-surgical method of locating these plaques, an IR fiber optic imaging system has been developed in our laboratory to evalute the causes and effect of heat in atherosclerotic plaques. The fiber optical imagin bundle consists of 900 individual As2S3 chalcogenide glass fibers which transmit IR radiation from 0.7 micrometers 7 micrometers with little energy loss. By combining that with a highly sensitive Indium Antimonide IR focal plane array detector, we are able to obtain thermal graphic images in situ. The temperature heterogeneity of atherosclerotic plaques developed in the arteral of the experimental animal models is under study with the new device. The preliminary experimental results from the animal model are encouraging. The potential of using this new technology in diagnostic evaluation of the vulnerable atherosclerotic plaques is considerable.

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

PubMed Central

Evans, J. W.; Singer, M.; Chapple, C. R.; Macartney, N.; Walker, J. M.; Milroy, E. J.

1992-01-01

OBJECTIVE--To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN--Controlled comparative study. SETTING--London teaching hospital. PATIENTS--33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES--Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS--In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS--Important haemodynamic disturbances were identified during routine apparently

Progress in atherosclerotic plaque imaging

PubMed Central

Soloperto, Giulia; Casciaro, Sergio

2012-01-01

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods. PMID:22937215

Influence of different computational approaches for stent deployment on cerebral aneurysm haemodynamics

PubMed Central

Bernardini, Annarita; Larrabide, Ignacio; Morales, Hernán G.; Pennati, Giancarlo; Petrini, Lorenza; Cito, Salvatore; Frangi, Alejandro F.

2011-01-01

Cerebral aneurysms are abnormal focal dilatations of artery walls. The interest in virtual tools to help clinicians to value the effectiveness of different procedures for cerebral aneurysm treatment is constantly growing. This study is focused on the analysis of the influence of different stent deployment approaches on intra-aneurysmal haemodynamics using computational fluid dynamics (CFD). A self-expanding stent was deployed in an idealized aneurysmatic cerebral vessel in two initial positions. Different cases characterized by a progression of simplifications on stent modelling (geometry and material) and vessel material properties were set up, using finite element and fast virtual stenting methods. Then, CFD analysis was performed for untreated and stented vessels. Haemodynamic parameters were analysed qualitatively and quantitatively, comparing the cases and the two initial positions. All the cases predicted a reduction of average wall shear stress and average velocity of almost 50 per cent after stent deployment for both initial positions. Results highlighted that, although some differences in calculated parameters existed across the cases based on the modelling simplifications, all the approaches described the most important effects on intra-aneurysmal haemodynamics. Hence, simpler and faster modelling approaches could be included in clinical workflow and, despite the adopted simplifications, support clinicians in the treatment planning. PMID:22670204

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

PubMed

Voswinckel, Robert; Reichenberger, Frank; Enke, Beate; Kreckel, Andre; Krick, Stefanie; Gall, Henning; Schermuly, Ralph Theo; Grimminger, Friedrich; Rubin, Lewis J; Olschewski, Horst; Seeger, Werner; Ghofrani, Hossein A

2008-10-01

Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations.

PubMed

Sacco, Federica; Paun, Bruno; Lehmkuhl, Oriol; Iles, Tinen L; Iaizzo, Paul A; Houzeaux, Guillaume; Vázquez, Mariano; Butakoff, Constantine; Aguado-Sierra, Jazmin

2018-06-11

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches employ smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band and papillary muscles (PMs). Four paired detailed and smoothed RV endocardium models (two male and two female) were reconstructed from ex-vivo human hearts high-resolution magnetic resonance images (MRI). Detailed models include structures with ≥1 mm 2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics (CFD) simulations with steady and transient inflows, using high performance computing (HPC). The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress (WSS). Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the WSS and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity. This article is protected by copyright. All rights reserved.

Continuous spinal anaesthesia with minimally invasive haemodynamic monitoring for surgical hip repair in two patients with severe aortic stenosis.

PubMed

López, María Mercedes; Guasch, Emilia; Schiraldi, Renato; Maggi, Genaro; Alonso, Eduardo; Gilsanz, Fernando

2016-01-01

Aortic stenosis increases perioperative morbidity and mortality, perioperative invasive monitoring is advised for patients with an aortic valve area <1.0 cm(2) or a mean aortic valve gradient >30 mmHg and it is important to avoid hypotension and arrhythmias. We report the anaesthetic management with continuous spinal anaesthesia and minimally invasive haemodynamic monitoring of two patients with severe aortic stenosis undergoing surgical hip repair. Two women with severe aortic stenosis were scheduled for hip fracture repair. Continuous spinal anaesthesia with minimally invasive haemodynamic monitoring was used for anaesthetic management of both. Surgery was performed successfully after two consecutive doses of 2mg of isobaric bupivacaine 0.5% in one of them and four consecutive doses in the other. Haemodynamic conditions remained stable throughout the intervention. Vital signs and haemodynamic parameters remained stable throughout the two interventions. Our report illustrates the use of continuous spinal anaesthesia with minimally invasive haemodynamic monitoring as a valid alternative to general or epidural anaesthesia in two patients with severe aortic stenosis who are undergoing lower limb surgery. However, controlled clinical trials would be required to establish that this technique is safe and effective in these type or patients. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

CANCER BIOMARKERS IN HUMAN ATHEROSCLEROTIC LESIONS: DETECTION OF DNA ADDUCTS

EPA Science Inventory

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abnormal aorta specimens taken at surgery from seven patients. NA adduc...

Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Huynh, Thuan G; Lord, Reginald S A; Grabs, Anthony J; Valenzuela, Stella M

2007-03-01

Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.

Assessing paedophilia based on the haemodynamic brain response to face images.

PubMed

Ponseti, Jorge; Granert, Oliver; Van Eimeren, Thilo; Jansen, Olav; Wolff, Stephan; Beier, Klaus; Deuschl, Günther; Huchzermeier, Christian; Stirn, Aglaja; Bosinski, Hartmut; Roman Siebner, Hartwig

2016-01-01

Objective assessment of sexual preferences may be of relevance in the treatment and prognosis of child sexual offenders. Previous research has indicated that this can be achieved by pattern classification of brain responses to sexual child and adult images. Our recent research showed that human face processing is tuned to sexual age preferences. This observation prompted us to test whether paedophilia can be inferred based on the haemodynamic brain responses to adult and child faces. Twenty-four men sexually attracted to prepubescent boys or girls (paedophiles) and 32 men sexually attracted to men or women (teleiophiles) were exposed to images of child and adult, male and female faces during a functional magnetic resonance imaging (fMRI) session. A cross-validated, automatic pattern classification algorithm of brain responses to facial stimuli yielded four misclassified participants (three false positives), corresponding to a specificity of 91% and a sensitivity of 95%. These results indicate that the functional response to facial stimuli can be reliably used for fMRI-based classification of paedophilia, bypassing the problem of showing child sexual stimuli to paedophiles.

Freedom Solo® versus Trifecta® bioprostheses: clinical and haemodynamic evaluation after propensity score matching.

PubMed

Cerqueira, Rui J; Raimundo, Renata; Moreira, Soraia; Saraiva, Francisca A; Andrade, Marta; Salgueiro, Elson; Almeida, Jorge; Amorim, Mário Jorge; Pinho, Paulo; Lourenço, André P; Leite-Moreira, Adelino

2018-01-16

The goal of this study was to compare the stentless Freedom Solo® (FS) and the stented Trifecta® (TF) aortic bioprostheses with regard to haemodynamic profile, left ventricular mass regression and early and late postoperative outcomes and survival. A longitudinal cohort study of consecutive patients undergoing aortic valve replacement (2009-16) with either the FS or TF at 1 centre was performed. Local databases and national records were queried. Prosthesis haemodynamics and left ventricular dimensions were obtained from postoperative echocardiograms. After propensity score matching (21 covariates), the Kaplan-Meier and competing risk analyses were performed for survival and the combined outcome of structural valve deterioration and endocarditis, respectively. Haemodynamics and mass regression were assessed by a mixed-effects model including propensity score as a covariate. From a total sample of 397 patients with the FS and 525 TF bioprostheses with a median follow-up time of 4.0 (2.2-6.0) and 2.4 (1.4-3.7) years, respectively, a matched sample of 329 pairs was obtained. Matched groups showed no differences in survival (hazard ratio = 1.04, 95% confidence interval = 0.69-1.56) or cumulative hazards of combined outcome (subdistribution hazard ratio = 0.54, 95% confidence interval = 0.21-1.39). Although the TF showed an improved haemodynamic profile, no difference was found in mass regression. Patients with TF bioprostheses had higher rates of prolonged mechanical ventilation, whereas patients with the FS bioprosthesis showed higher rates of thrombocytopenia. The TF showed an improved haemodynamic profile compared to the FS, but this did not translate into further reverse remodelling. Postoperative outcomes and survival rates were comparable for both bioprostheses. Long-term follow-up is needed for comparisons with classical bioprosthesis models. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for

Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial

PubMed Central

Ehlken, Nicola; Lichtblau, Mona; Klose, Hans; Weidenhammer, Johannes; Fischer, Christine; Nechwatal, Robert; Uiker, Sören; Halank, Michael; Olsson, Karen; Seeger, Werner; Gall, Henning; Rosenkranz, Stephan; Wilkens, Heinrike; Mertens, Dirk; Seyfarth, Hans-Jürgen; Opitz, Christian; Ulrich, Silvia; Egenlauf, Benjamin; Grünig, Ekkehard

2016-01-01

Abstract Aims The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients. Methods and results Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control −0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training. Conclusion Low-dose exercise training at 4–7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results. PMID:26231884

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

PubMed

Tautenhahn, Hans-Michael; Brückner, Sandra; Uder, Christiane; Erler, Silvio; Hempel, Madlen; von Bergen, Martin; Brach, Janine; Winkler, Sandra; Pankow, Franziska; Gittel, Claudia; Baunack, Manja; Lange, Undine; Broschewitz, Johannes; Dollinger, Matthias; Bartels, Michael; Pietsch, Uta; Amann, Kerstin; Christ, Bruno

2017-06-01

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

PubMed

Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.

PubMed

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-11-18

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.

PubMed

Fetterman, Jessica L; Holbrook, Monica; Westbrook, David G; Brown, Jamelle A; Feeley, Kyle P; Bretón-Romero, Rosa; Linder, Erika A; Berk, Brittany D; Weisbrod, Robert M; Widlansky, Michael E; Gokce, Noyan; Ballinger, Scott W; Hamburg, Naomi M

2016-03-31

Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.

Investigating the influence of haemodynamic stimuli on intracranial aneurysm inception.

PubMed

Chen, Haoyu; Selimovic, Alisa; Thompson, Harry; Chiarini, Alessandro; Penrose, Justin; Ventikos, Yiannis; Watton, Paul N

2013-07-01

We propose a novel method to reconstruct the hypothetical geometry of the healthy vasculature prior to intracranial aneurysm (IA) formation: a Frenet frame is calculated along the skeletonization of the arterial geometry; upstream and downstream boundaries of the aneurysmal segment are expressed in terms of the local Frenet frame basis vectors; the hypothetical healthy geometry is then reconstructed by propagating a closed curve along the skeleton using the local Frenet frames so that the upstream boundary is smoothly morphed into the downstream boundary. This methodology takes into account the tortuosity of the arterial vasculature and requires minimal user subjectivity. The method is applied to 22 clinical cases depicting IAs. Computational fluid dynamic simulations of the vasculature without IA are performed and the haemodynamic stimuli in the location of IA formation are examined. We observe that locally elevated wall shear stress (WSS) and gradient oscillatory number (GON) are highly correlated (20/22 for WSS and 19/22 for GON) with regions susceptible to sidewall IA formation whilst haemodynamic indices associated with the oscillation of the WSS vectors have much lower correlations.

Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

PubMed

Wu, Min; Fw van der Steen, Antonius; Regar, Evelyn; van Soest, Gijs

2016-10-01

The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo . Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

NASA Astrophysics Data System (ADS)

Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

2012-10-01

Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension

PubMed Central

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N.; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J.; Sastry, B.K.S.; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-01-01

Aims The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Methods and results Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28–0.86; HR 0.72, 95% CL 0.42–1.22; and HR 0.22, 95% CL 0.15–0.33, respectively). Conclusions For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. PMID:28329315

SERAPHIN haemodynamic substudy: the effect of the dual endothelin receptor antagonist macitentan on haemodynamic parameters and NT-proBNP levels and their association with disease progression in patients with pulmonary arterial hypertension.

PubMed

Galiè, Nazzareno; Jansa, Pavel; Pulido, Tomás; Channick, Richard N; Delcroix, Marion; Ghofrani, Hossein-Ardeschir; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loïc; Rubin, Lewis J; Sastry, B K S; Simonneau, Gérald; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam

2017-04-14

The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28-0.86; HR 0.72, 95% CL 0.42-1.22; and HR 0.22, 95% CL 0.15-0.33, respectively). For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality. © The Author 2017. Published on behalf of the European Society of Cardiology

Short communication: Dating components of human atherosclerotic plaques.

PubMed

Gonçalves, Isabel; Stenström, Kristina; Skog, Göran; Mattsson, Sören; Nitulescu, Mihaela; Nilsson, Jan

2010-04-02

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

PubMed Central

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-01-01

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research. PMID:29156574

A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

PubMed Central

Sultan, Salahaden R.; Millar, Sophie A.; England, Timothy J.; O'Sullivan, Saoirse E.

2017-01-01

Despite cannabidiol (CBD) having numerous cardiovascular effects in vitro, its haemodynamic effects in vivo are unclear. Nonetheless, the clinical use of CBD (Epidiolex) is becoming more widespread. The aim of this systematic review was to establish whether CBD is associated with changes in haemodynamics in vivo. Twenty-five studies that assessed the haemodynamic effects of CBD (from PubMed, Medline and EMBASE) were systematically reviewed and meta-analyzed. Data on blood pressure (BP), heart rate (HR), and blood flow (BF) were extracted and analyzed using random effects models. Twenty-two publications assessed BP and HR among 6 species (BP n = 344 and HR n = 395), and 5 publications assessed BF in 3 species (n = 56) after acute dosing of CBD. Chronic dosing was assessed in 4 publications in 3 species (total subjects BP, n = 6; HR, n = 27; BF, n = 3). Acute CBD dosing had no effect on BP or HR under control conditions. Similarly, chronic dosing with CBD had no effect on HR. In models of stress, acute CBD administration significantly reduced the increase in BP and HR induced by stress (BP, mean difference (MD) −3.54, 95% CI −5.19, −1.9, p < 0.0001; HR, MD −16.23, 95% CI −26.44, −6.02, p = 0.002). In mouse models of stroke, CBD significantly increased cerebral blood flow (CBF, standardized mean difference (SMD) 1.62, 95% CI 0.41, 2.83, p = 0.009). Heterogeneity among the studies was present, there was no publication bias except in HR of control and stressful conditions after acute CBD dosing, and median study quality was 5 out of 9 (ranging from 1 to 8). From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke. Further studies are required to fully understand the potential haemodynamic effects of CBD in humans under normal and pathological conditions. PMID

A comparison of head motion and prefrontal haemodynamics during upright and recumbent cycling exercise.

PubMed

Tempest, Gavin D; Eston, Roger G; Parfitt, Gaynor

2017-11-01

The aim of this observational study was to compare head motion and prefrontal haemodynamics during exercise using three commercial cycling ergometers. Participants (n = 12) completed an incremental exercise test to exhaustion during upright, recumbent and semi-recumbent cycling. Head motion (using accelerometry), physiological data (oxygen uptake, end-tidal carbon dioxide [P ET CO 2 ] and heart rate) and changes in prefrontal haemodynamics (oxygenation, deoxygenation and blood volume using near infrared spectroscopy [NIRS]) were recorded. Despite no difference in oxygen uptake and heart rate, head motion was higher and P ET CO 2 was lower during upright cycling at maximal exercise (P<0·05). Analyses of covariance (covariates: head motion P>0·05; P ET CO 2 , P<0·01) revealed that prefrontal oxygenation was higher during semi-recumbent than recumbent cycling and deoxygenation and blood volume were higher during upright than recumbent and semi-recumbent cycling (respectively; P<0·05). This work highlights the robustness of the utility of NIRS to head motion and describes the potential postural effects upon the prefrontal haemodynamic response during upright and recumbent cycling exercise. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients.

PubMed

Matamis, D; Tsagourias, M; Koletsos, K; Riggos, D; Mavromatidis, K; Sombolos, K; Bursztein, S

1994-07-01

To investigate the influence of continuous haemofiltration (CHF) on haemodynamics, gas exchange and core temperature in critically ill septic patients with acute renal failure. In 20 patients (17 male, 3 female) ultrafiltration rate, core temperature, gas exchange and haemodynamic variables were measured at regular intervals during the first 48 h of haemofiltration. Baseline data were compared to those obtained 30 min after initiating CHF and also to those during hypothermia (if observed). Haemodynamic variables remained remarkably constant throughout the study period. In patients with a relatively low ultrafiltration rate (855 +/- 278 ml/h) temperature did not change, while in patients with a high ultrafiltration rate (1468 +/- 293 ml/h) core temperature significantly decreased from 37.6 +/- 0.9 degrees C to 34.8 +/- 0.8 degrees C (p < 0.001). There was a statistically significant correlation between temperature decrease and ultrafiltration rate (r = -0.68, Y = 1.8-0.003 X, p < 0.01). Hypothermic patients also showed a mean decrease in VO2 from 141 +/- 22 ml/min/m2 to 112 +/- 22 ml/min/m2 (p < 0.01) with a concomitant increase in PaO2 from 103 +/- 37 mmHg to 140 +/- 42 mmHg (p < 0.001) and in PvO2 from 35 +/- 4 mmHg to 41 +/- 5 mmHg (p < 0.001). 1) Continuous haemofiltration does not cause significant alternations in haemodynamic variables. 2) Hypothermia frequently occurs in patients undergoing continuous haemofiltration with high ultrafiltration rates. These hypothermic patients show a reduction in VO2 leading to an increase in PvO2 and PaO2. This mild hypothermia in these circumstances has no evident deleterious effects.

Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

2016-12-01

A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

How to manage hypertension with atherosclerotic renal artery stenosis?

PubMed

Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

2017-04-01

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

PubMed Central

Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients.

PubMed

Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 ( Campylobacter rectus , Porphyromonas gingivalis , Porphyromonas endodontalis , Prevotella intermedia , Prevotella nigrescens ) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

Human haemodynamic frequency harmonics regulate the inflammatory phenotype of vascular endothelial cells.

PubMed

Feaver, Ryan E; Gelfand, Bradley D; Blackman, Brett R

2013-01-01

Haemodynamic variations are inherent to blood vessel geometries (such as bifurcations) and correlate with regional development of inflammation and atherosclerosis. However, the complex frequency spectrum characteristics from these haemodynamics have never been exploited to test whether frequency variations are critical determinants of endothelial inflammatory phenotype. Here we utilize an experimental Fourier transform analysis to systematically manipulate individual frequency harmonics from human carotid shear stress waveforms applied in vitro to human endothelial cells. The frequency spectrum, specifically the 0 th and 1st harmonics, is a significant regulator of inflammation, including NF-κB activity and downstream inflammatory phenotype. Further, a harmonic-based regression-model predicts eccentric NF-κB activity observed in the human internal carotid artery. Finally, short interfering RNA-knockdown of the mechanosensor PECAM-1 reverses frequency-dependent regulation of NF-κB activity. Thus, PECAM-1 may have a critical role in the endothelium's exquisite sensitivity to complex shear stress frequency harmonics and provide a mechanism for the focal development of vascular inflammation.

64Cu-Labeled Divalent Cystine Knot Peptide for Imaging Carotid Atherosclerotic Plaques.

PubMed

Jiang, Lei; Tu, Yingfeng; Kimura, Richard H; Habte, Frezghi; Chen, Hao; Cheng, Kai; Shi, Hongcheng; Gambhir, Sanjiv Sam; Cheng, Zhen

2015-06-01

The rupture of vulnerable atherosclerotic plaques that lead to stroke and myocardial infarction may be induced by macrophage infiltration and augmented by the expression of integrin αvβ3. Indeed, atherosclerotic angiogenesis may be a promising marker of inflammation. In this study, an engineered integrin αvβ3-targeting PET probe, (64)Cu-NOTA-3-4A, derived from a divalent knottin miniprotein was evaluated in a mouse model for carotid atherosclerotic plaques. Atherosclerotic plaques in BALB/C mice, maintained on a high-fat diet, were induced with streptozotocin injection and carotid artery ligation and verified by MR imaging. Knottin 3-4A was synthesized by solid-phase peptide synthesis chemistry and coupled to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) before radiolabeling with (64)Cu. PET probe stability in mouse serum was evaluated. Mice with carotid atherosclerotic plaques were injected via the tail vein with (64)Cu-NOTA-3-4A or (18)F-FDG, followed by small-animal PET/CT imaging at different time points. Receptor targeting specificity of the probe was verified by coinjection of c(RGDyK) administered in molar excess. Subsequently, carotid artery dissection and immunofluorescence staining were performed to evaluate target expression. (64)Cu-NOTA-3-4A was synthesized in high radiochemical purity and yield and demonstrated molecular stability in both phosphate-buffered saline and mouse serum at 4 h. Small-animal PET/CT showed that (64)Cu-NOTA-3-4A accumulated at significantly higher levels in the neovasculature of carotid atherosclerotic plaques (7.41 ± 1.44 vs. 0.67 ± 0.23 percentage injected dose/gram, P < 0.05) than healthy or normal vessels at 1 h after injection. (18)F-FDG also accumulated in atherosclerotic lesions at 0.5 and 1 h after injection but at lower plaque-to-normal tissue ratios than (64)Cu-NOTA-3-4A. For example, plaque-to-normal carotid artery ratios for (18)F-FDG and (64)Cu-NOTA-3-4A at 1 h after injection were 3.75 and 14.71 (P < 0

Near-infrared hyperspectral imaging of atherosclerotic plaque in WHHLMI rabbit artery

NASA Astrophysics Data System (ADS)

Ishii, Katsunori; Kitayabu, Akiko; Omiya, Kota; Honda, Norihiro; Awazu, Kunio

2013-03-01

Hyperspectral imaging (HSI) of rabbit atherosclerotic plaque in near-infrared (NIR) range from 1150 to 2400 nm was demonstrated. A method to identify vulnerable plaques that are likely to cause acute coronary events has been required. The object of this study is identifying vulnerable plaques by NIR-HSI for an angioscopic application. In this study, we observed the hyperspectral images of the atherosclerotic plaque in WHHLMI rabbit (atherosclerotic rabbit) artery under simulated angioscopic conditions by NIR-HSI. NIR-HSI system was constructed by a NIR super continuum light and a mercury-cadmium-telluride camera. Spectral absorbance values (log (1/R) data) were obtained in the wavelength range from 1150 to 2400 nm at 10 nm intervals. The hyperspectral images were constructed with spectral angle mapper algorithm. As a result, the detections of atherosclerotic plaque under angioscopic observation conditions were achieved especially in the wavelength around 1200 nm, which corresponds to the second overtone of CH stretching vibration mode. The NIR-HSI was considered to serve as an angioscopic diagnosis technique to identify vulnerable plaques without clamping and saline injection.

Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

PubMed Central

Karanikola, Evridiki; Karaolanis, Georgios; Galyfos, George; Barbaressos, Emmanuel; Palla, Viktoria; Filis, Konstantinos

2017-01-01

Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice. PMID:28377906

Detection of High-Risk Atherosclerotic Plaque

PubMed Central

Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

2013-01-01

The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

PubMed Central

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

PubMed

Radaelli, A G; Augsburger, L; Cebral, J R; Ohta, M; Rüfenacht, D A; Balossino, R; Benndorf, G; Hose, D R; Marzo, A; Metcalfe, R; Mortier, P; Mut, F; Reymond, P; Socci, L; Verhegghe, B; Frangi, A F

2008-07-19

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and

Dexmedetomidine in Attenuation of Haemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study

PubMed Central

Bhagat, Nandlal; Karim, Habib Md Reazaul; Hajong, Ranendra; Bhattacharyya, Prithwis; Singh, Manorama

2016-01-01

Introduction Perioperative procedures are stressful and lead to haemodynamic instability with potentially devastating consequences. Dexmedetomidine is found to have many of the desired characteristics that are required in perioperative period. Aim To evaluate the ability of pre and intraoperative dexmedetomidine to attenuate stress induced haemodynamic responses, quantifying the anaesthetic agents sparing as well as its cost-effectiveness in patients undergoing laparoscopic cholecystectomy. Materials and Methods The present single blind randomized study was conducted with 120 ASA I and II consented patients who underwent laparoscopic cholecystectomy. Patients were randomly divided into 2 groups (i.e., group D and group N). Prior to induction, group D received 1 μg/kg of Dexmedetomidine and group N received Normal saline infusion over 20 minutes. Group D also received maintenance Dexmedetomidine intraoperatively. Bispectral index and minimum alveolar concentration monitoring was done in both the groups. Haemodynamic parameters were noted till 100 minutes post laryngoscopy. Opioid and anaesthetic agent consumptions were also noted and cost analysis was done. Medcalc–Version 12.5.0.0 software was used for statistics and p <0.05 was considered significant. Results Dexmedetomidine attenuated the stress induced haemodynamics responses and produced stable, relatively non fluctuating haemodynamics throughout. The Minimum Alveolar Concentration (MAC) requirement and the consumptions of Fentanyl and Isoflurane were significantly less in the Dexmedetomidine group (p<0.0001). However, despite anaesthetic dose sparing effect the anaesthetic technique was not cost-effective. Conclusion Dexmedetomidine is effective in attenuating haemodynamic responses in laparoscopic surgery and having dose sparing effect on Fentanyl, Propofol and Isoflurane. However, overall this technique is not cost-effective. PMID:28050479

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

PubMed Central

Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

2017-01-01

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

Flow in Atherosclerotic Blood Vessels

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Stroud, Jenn S.

2000-11-01

Atherosclerotic lesions occur in arteries where there are major changes in flow structure, e.g. bifurcations and junctions. The reduction of vessel lumen alters the flow, including the mechanical forces on the walls. We have examined the flow in carotid artery bifurcations with realistic plaque contours. The unsteady, incompressible, Navier-Stokes equations are solved in finite-volume form. Steady and pulsatile flows have been analyzed for laminar and turbulent flows, using for the latter a low-Reynolds number k- ɛ model and a k-ω model. Non-Newtonian viscosity is also considered using a power-law model. In general the very irregular contours of the vessels lead to recirculating regions, strong spatial variations of wall shear stresses, and in some cases, vortex shedding. Even steady inlet flow exhibits fluctuating, unsteady behavior. Neither turbulence models captures all the physics of the flow. The flow, in fact, appears to be transitional and not fully turbulent. For unsteady flow, there are also strong temporal variations of normal and shear stresses, which together with the strong spatial variations, has important implications for the onset and progression of atherosclerotic disease.

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy

PubMed Central

Small, David M.; Jones, Jason S.; Tendler, Irwin I.; Miller, Paul E.; Ghetti, Andre; Nishimura, Nozomi

2017-01-01

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool. PMID:29359098

Association between abdominal fat distribution and atherosclerotic changes in the carotid artery.

PubMed

Oike, Miki; Yokokawa, Hirohide; Fukuda, Hiroshi; Haniu, Tomomi; Oka, Fukuko; Hisaoka, Teruhiko; Isonuma, Hiroshi

2014-01-01

We aimed to evaluate the association between abdominal fat distribution (e.g., abdominal visceral fat area [VFA], subcutaneous fat area [SFA], and total fat area [TFA]), waist circumference (WC), or body mass index (BMI) and atherosclerotic changes in the carotid artery after adjusting for common risk factors. The present study is a hospital-based, cross-sectional study. Study participants included 223 Japanese individuals who underwent a medical health checkup at Juntendo University Hospital, Tokyo, between December 2005 and August 2011. Multivariate logistic regression analysis was used to examine the association between abdominal VFA, SFA, TFA, the VFA/SFA ratio, WC, or BMI and intima-media thickness [IMT] (mean IMT≥1.1mm or maximum IMT≥1.2mm) as atherosclerotic changes in the carotid artery. Multivariate logistic regression analysis showed that VFA (OR for ≥150cm(2) versus <100cm(2), 3.88; 95% CI, 1.39-10.85), BMI (OR for ≥27.6kg/m(2) versus <25kg/m(2), 5.22; 95% CI, 1.69-16.16), and TFA (OR for 200-285cm(2) versus <200cm(2), 4.15; 95% CI, 1.34-12.86: OR for ≥285cm(2) versus <200cm(2), 5.53; 95% CI, 1.76-17.35) were significantly associated with atherosclerotic changes in men. After adjustment for BMI, only TFA (OR for ≥285cm(2) versus <200cm(2), 3.76; 95%CI, 1.03-13.79) in men was significantly associated with atherosclerotic changes in the carotid artery. Our results indicate that VFA, TFA, and BMI are independently associated with atherosclerotic changes in Japanese men. TFA may be considered as a valuable measure of atherosclerotic changes. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

NASA Astrophysics Data System (ADS)

Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

2013-06-01

Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

PubMed

Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

PubMed

Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

2017-10-01

Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (<40% lipid core plaque area; n=6) or unstable (≥40% lipid core plaque area; n=14) based on histopathological examinations of hematoxylin and eosin stained sections. The expression of Cat K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

PubMed

Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

PubMed Central

Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

2015-01-01

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

Comparison of the Haemodynamic Effects of Three Different Methods at the Induction of Anaesthesia

PubMed Central

Uygur, Mehmet Levent; Ersoy, Ayşın; Altan, Aysel; Ervatan, Zekeriya; Kamalı, Sedat

2014-01-01

Objective Haemodynamic variations are inevitable during induction of anaesthetic drugs. The present study investigates the haemodynamic variations of three different drugs (thiopental, propofol, and etomidate) used for induction of general anaesthesia together with fentanyl. Methods In a randomized, double-blind study, 45 patients were assigned to one of three groups (n=15 each). Fentanyl 1 μg kg−1 was injected over 60 sec followed by propofol 2 mg kg−1 (Group P), thiopentone 6 mg kg−1 (Group T), or etomidate 0.3 mg kg−1 (Group E). Noninvasive measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and heart rate (HR) was performed on admittance, immediately before the induction of anaesthesia, and 1, 3, and 5 min thereafter. Cardiac output (CO) values were recorded before induction, immediately after the injection of the drug, and at 1 min after the intubation. Results In all groups, during the study period, SAP, DAP, MAP, and CO values decreased with respect to time before induction. Following the administration of the induction dose of propofol (Group P), a significantly greater decrease of systolic and diastolic blood pressure was observed with etomidate (Group E) or thiopentone (Group T). Decrease in CO was also more marked with propofol (Group P) than with etomidate (Group E) or thiopentone (Group T). Conclusion It’s concluded that, in this study, the combination of fentanyl-etomidate is safer than both the groups of fentanyl-propofol and fentanyl-thiopental in terms of providing haemodynamic stability. PMID:27366443

Quantitative analysis of the polarization characteristics of atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Kirillin, Michail Y.; Dudenkova, Varvara V.; Kiseleva, Elena B.; Moiseev, Alexander A.; Gelikonov, Grigory V.; Timofeeva, Lidia B.; Fiks, Ilya I.; Feldchtein, Felix I.; Gladkova, Natalia D.

2016-04-01

In this study we demonstrate the capability of cross-polarization optical coherence tomography (CP OCT) to assess collagen and elastin fibers condition in atherosclerotic plaques basing on ratio of the OCT signal levels in cross- and co- polarizations. We consider the depolarization factor (DF) and the effective birefringence (Δn) as quantitative characteristics of CP OCT images. We revealed that calculation of both DF and Δn in the region of interest (fibrous cap) yields a statistically significant difference between stable and unstable plaques (0.46+/-0.21 vs 0.09+/-0.04 for IDF; (4.7+/-1.0)•10-4 vs (2.5+/-0.7)•10-4 for Δn p<0.05). In parallel with CP OCT we used the nonlinear microscopy for analysis of thin cross-section of atherosclerotic plaque, revealing the different average isotropy index of collagen and elastin fibers for stable and unstable plaques (0.30 +/- 0.10 vs 0.70 +/- 0.08; p<0.001). The proposed approach for quantitative assessment of CP OCT images allows cross-scattering and birefringence characterization of stable and unstable atherosclerotic plaques.

Lower limb atherosclerotic disease causes various deteriorations of patients' health-related quality of life.

PubMed

Koivunen, Kirsi; Lukkarinen, Hannele

2006-12-01

Lower limb atherosclerotic disease (LLAD) is a worldwide health problem. Approximately 100,000 Finns have LLAD. Currently, a large number of health-related quality of life (HRQoL) studies are available, but we still have scant comprehensive information of HRQoL of patients with LLAD. The aim was to describe the HRQoL of women and men with LLAD in relation to the age- and sex-matched general population. In addition, the purpose was to study which demographic and relevant clinical and psychologic factors are connected with HRQoL of patients with LLAD. Patients with LLAD (N = 180, 62 women and 118 men) were recruited to participate in this study in the Clinic of Surgery, Oulu University Hospital, from 2001 to 2004. The control sample consisted of an age- and sex-matched general population (N = 2126; 1081 women and 1045 men). The HRQoL of the women and men with LLAD was evaluated using the Nottingham Health Profile (NHP) instrument, in relation to an age- and sex-matched general population (N = 2126) as well as demographic and relevant clinical and psychologic factors. The HRQoL of men was significantly (P < .05) poorer on all dimensions of the NHP instrument in the age groups 55 to 74 years. HRQoL was also clearly affected in the youngest age group of men on the dimensions of pain (P < .05) and mobility (P < .05) and further in the oldest age group on the dimension of energy (P < .05). The HRQoL of women with LLAD was only significantly poorer (P < .05) on the dimension of pain in the age group of 65 to 74 years than the HRQoL of age-matched Finnish women. The most emphasized relationships between poor HRQoL and the demographic, relevant clinical and psychologic factors were male sex, lack of exercise, retirement, a short painless walking distance, other atherosclerotic disease, poor subjective health status, problems with ability to cope at home, problems with the treatment of illness, and sex life. Male patients with LLAD had poorer HRQoL than the corresponding

Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice

PubMed Central

Fraga-Silva, Rodrigo A.; Montecucco, Fabrizio; Costa-Fraga, Fabiana P.; Nencioni, Alessio; Caffa, Irene; Bragina, Maiia E.; Mach, François; Raizada, Mohan K.; Santos, Robson A.S.; da Silva, Rafaela F.; Stergiopulos, Nikolaos

2017-01-01

Angiotensin (Ang) II contributes to the development of atherosclerosis, while Ang-(1–7) has atheroprotective actions. Accordingly, angiotensin-converting enzyme 2 (ACE2), which breaks-down Ang II and forms Ang-(1–7), has been suggested as a target against atherosclerosis. Here we investigated the actions of diminazene, a recently developed ACE2 activator compound, in a model of vulnerable atherosclerotic plaque. Atherosclerotic plaque formation was induced in the carotid artery of ApoE-deficient mice by a shear stress (SS) modiffer device. The animals were treated with diminazene (15 mg/kg/day) or vehicle. ACE2 was strongly expressed in the aortic root and low SS-induced carotid plaques, but poorly expressed in the oscillatory SS-induced carotid plaques. Diminazene treatment did not change the lesion size, but ameliorated the composition of aortic root and low SS-induced carotid plaques by increasing collagen content and decreasing both MMP-9 expression and macrophage infiltration. Interestingly, these beneficial effects were not observed in the oscillatory SS-induced plaque. Additionally, diminazene treatment decreased intraplaque ICAM-1 and VCAM-1 expression, circulating cytokine and chemokine levels and serum triglycerides. In summary, ACE2 was distinctively expressed in atherosclerotic plaques, which depends on the local pattern of shear stress. Moreover, diminazene treatment enhances the stability of atherosclerotic plaques. PMID:26304699

HACE1-dependent protein degradation provides cardiac protection in response to haemodynamic stress

NASA Astrophysics Data System (ADS)

Zhang, Liyong; Chen, Xin; Sharma, Parveen; Moon, Mark; Sheftel, Alex D.; Dawood, Fayez; Nghiem, Mai P.; Wu, Jun; Li, Ren-Ke; Gramolini, Anthony O.; Sorensen, Poul H.; Penninger, Josef M.; Brumell, John H.; Liu, Peter P.

2014-03-01

The HECT E3 ubiquitin ligase HACE1 is a tumour suppressor known to regulate Rac1 activity under stress conditions. HACE1 is increased in the serum of patients with heart failure. Here we show that HACE1 protects the heart under pressure stress by controlling protein degradation. Hace1 deficiency in mice results in accelerated heart failure and increased mortality under haemodynamic stress. Hearts from Hace1-/- mice display abnormal cardiac hypertrophy, left ventricular dysfunction, accumulation of LC3, p62 and ubiquitinated proteins enriched for cytoskeletal species, indicating impaired autophagy. Our data suggest that HACE1 mediates p62-dependent selective autophagic turnover of ubiquitinated proteins by its ankyrin repeat domain through protein-protein interaction, which is independent of its E3 ligase activity. This would classify HACE1 as a dual-function E3 ligase. Our finding that HACE1 has a protective function in the heart in response to haemodynamic stress suggests that HACE1 may be a potential diagnostic and therapeutic target for heart disease.

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin

PubMed Central

Tahvanainen, Anna; Leskinen, Miia; Koskela, Jenni; Ilveskoski, Erkki; Alanko, Juha; Kähönen, Mika; Kööbi, Tiit; Lehtimäki, Lauri; Moilanen, Eeva; Mustonen, Jukka; Pörsti, Ilkka

2009-01-01

AIMS To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright

A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation.

PubMed

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-10-07

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE(-)(/)(-) mice before the development of manifest atherosclerotic lesions. Platelet-endothelial cell interaction involved both platelet glycoprotein (GP)Ibalpha and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE(-)(/)(-) mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

Cardiac autonomic and haemodynamic recovery after a single session of aerobic exercise with and without blood flow restriction in older adults.

PubMed

Ferreira, Marina Lívia Venturini; Sardeli, Amanda Veiga; Souza, Giovana Vergínia De; Bonganha, Valéria; Santos, Lucas Do Carmo; Castro, Alex; Cavaglieri, Cláudia Regina; Chacon-Mikahil, Mara Patrícia Traina

2017-12-01

This study investigated the autonomic and haemodynamic responses to different aerobic exercise loads, with and without blood flow restriction (BFR). In a crossover study, 21 older adults (8 males and 13 females) completed different aerobic exercise sessions: low load without BFR (LL) (40% VO 2 max ), low load with BFR (LL-BFR) (40% VO 2 max + 50% BFR) and high load without BFR (HL) (70% VO 2 max ). Heart rate variability and haemodynamic responses were recorded during rest and throughout 30 min of recovery. HL reduced R-R interval, the root mean square of successive difference of R-R intervals and high frequency during 30 min of recovery at a greater magnitude compared with LL and LL-BFR. Sympathetic-vagal balance increased the values for HL during 30 min of recovery at a greater magnitude when compared with LL and LL-BFR. Post-exercise haemodynamic showed reduced values of double product at 30 min of recovery compared to rest in LL-BFR, while HL showed higher values compared to rest, LL-BFR and LL. Reduced systolic blood pressure was observed for LL-BFR (30 min) compared to rest. Autonomic and haemodynamic responses indicate lower cardiovascular stress after LL-BFR compared to HL, being this method, besides the functional adaptations, a potential choice to attenuate the cardiovascular stress after exercise in older adults.

Non-invasive evaluation of the haemodynamic effects of high-dose medetomidine in healthy cats for semen collection.

PubMed

Romagnoli, Noemi; Zambelli, Daniele; Cunto, Marco; Lambertini, Carlotta; Ventrella, Domenico; Baron Toaldo, Marco

2016-04-01

This study aimed to assess non-invasively the cardiovascular effects of high-dose medetomidine on healthy male cats undergoing semen collection. Haemodynamic evaluations were assessed on the basis of clinical examination, systolic arterial pressure (SAP) and transthoracic echocardiographic examination. Eight client owned, male domestic shorthair cats were sedated with a bolus of medetomidine intramuscularly (IM; 0.13 mg/kg), and semen collection was performed. A second transthoracic echocardiographic examination and SAP measurement were carried out 15 mins after sedation. At the end of the examination, the patients received a bolus of atipamezole (0.3 mg/kg) IM. The cats were deeply sedated, relaxed and laterally recumbent during the entire procedure. No rhythm abnormalities were observed during the examinations and no significant increase in SAP was recorded. Heart rate dropped from 200 ± 33 to 92 ± 13.1 beats per min after sedation. There was a significant increase in left ventricular dimensions and the left atrial area. The parameters of left ventricular systolic function were reduced, as were systemic and pulmonary cardiac outputs. Peak diastolic wave velocities were significantly reduced, while isovolumic contraction and relaxation time of the left ventricle were prolonged. Aortic valve insufficiency was recorded for all cats, while mitral valve insufficiency was noted in five cats. None of the subjects developed systolic anterior motion of the mitral valve. The protocol allowed us to collect good semen samples in healthy cats. However, high-dose medetomidine induces significant haemodynamic effects on the feline heart, mainly due to a reduced heart rate, an increased cardiac preload and impaired systolic function. The animals recovered from the anaesthesia, after antagonist administration, without showing any clinically relevant consequences. © ISFM and AAFP 2015.

Characterization of atherosclerotic plaques by cross-polarization optical coherence tomography

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Dudenkova, Varvara V.; Feldchtein, Felix I.; Timofeeva, Lidia B.; Kiseleva, Elena B.; Kuznetsov, Sergei S.; Moiseev, Alexander A.; Gelikonov, Gregory V.; Vitkin, Alex I.; Gladkova, Natalia D.

2016-02-01

We combined cross-polarization optical coherence tomography (CP OCT) and non-linear microscopy based on second harmonic generation (SHG) and two-photon-excited fluorescence (2PEF) to assess collagen and elastin fibers in the development of the atherosclerotic plaque (AP). The study shows potential of CP OCT for the assessment of collagen and elastin fibers condition in atherosclerotic arteries. Specifically, the additional information afforded by CP OCT, related to birefringence and cross-scattering properties of arterial tissues, may improve the robustness and accuracy of assessment about the microstructure and composition of the plaque for different stages of atherosclerosis.

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

NASA Astrophysics Data System (ADS)

Tearney, Guillermo J.; Bouma, Brett E.

2002-04-01

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (τ = 40 ms) versus stable plaques (τ = 400 ms) and normal aorta (τ = 500 ms). These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.

Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions).

PubMed

Maurovich-Horvat, Pál; Tárnoki, Dávid L; Tárnoki, Ádám D; Horváth, Tamás; Jermendy, Ádám L; Kolossváry, Márton; Szilveszter, Bálint; Voros, Viktor; Kovács, Attila; Molnár, Andrea Á; Littvay, Levente; Lamb, Hildo J; Voros, Szilard; Jermendy, György; Merkely, Béla

2015-12-01

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders. © 2015 Wiley Periodicals, Inc.

Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic plaque imaging agent in experimental models.

PubMed

Cao, Wei; Zhang, Yongxue; An, Rui

2006-01-01

The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/- 1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Near-infrared hyperspectral imaging of atherosclerotic tissue phantom

NASA Astrophysics Data System (ADS)

Ishii, K.; Nagao, R.; Kitayabu, A.; Awazu, K.

2013-06-01

A method to identify vulnerable plaques that are likely to cause acute coronary events has been required. The object of this study is identifying vulnerable plaques by hyperspectral imaging in near-infrared range (NIR-HSI) for an angioscopic application. In this study, NIR-HSI of atherosclerotic tissue phantoms was demonstrated under simulated angioscopic conditions. NIR-HSI system was constructed by a NIR super continuum light and a mercury-cadmium-telluride camera. Spectral absorbance values were obtained in the wavelength range from 1150 to 2400 nm at 10 nm intervals. The hyperspectral images were constructed with spectral angle mapper algorithm. As a result, detections of the lipid area in the atherosclerotic tissue phantom under angioscopic observation conditions were achieved especially in the wavelength around 1200 nm, which corresponds to the second overtone of CH stretching vibration mode.

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery.

PubMed

Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kawamoto, Chiaki; Uchida, Eiji; Kumita, Shin-Ichiro

2017-06-01

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

PubMed Central

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-01-01

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE − / − mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE − / − mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process. PMID:12370251

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

PubMed

Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

2013-05-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

The effect of low molecular weight dextran on haemodynamics and respiratory function during endotoxin-induced shock.

PubMed Central

Christenson, J T; al-Sarraf, A; Abu-Saleh, R

1992-01-01

The effects of low molecular weight dextran (LMWD) infusion, on gas exchange and haemodynamics were evaluated in sheep during endotoxin shock. The infusion of LMWD was started after signs of shock and lung injury were evident. After a stabilization period 10 micrograms kg-1 E. Coli endotoxin was infused i.v.. Endotoxin infusion resulted in an marked increase in pulmonary artery pressure (PAP) and decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2l). After 3 h MAP, PaO2, DO2l and compliance improved significantly in LMWD treated animals. The PAP had also decreased significantly in the LMWD-treated animals, but remained high in the controls (P less than 0.01). It was concluded that LMWD infusion improves haemodynamics and gas-exchange in sheep during endotoxin shock. PMID:1373624

Effects of active recovery on autonomic and haemodynamic responses after aerobic exercise.

PubMed

Soares, Antonio H G; Oliveira, Tiago P; Cavalcante, Bruno R; Farah, Breno Q; Lima, Aluísio H R A; Cucato, Gabriel G; Cardoso, Crivaldo G; Ritti-Dias, Raphael M

2017-01-01

The aim of this study was to examine the effect of active recovery on autonomic and haemodynamic responses after exercise in healthy adults. Nineteen healthy young male individuals underwent two experimental sessions: exercise with active recovery (AR) and exercise with passive recovery (PR). The exercise sessions comprised three phases: warm-up (5 min), exercise phase (cycle ergometer, 30 min, intensity between 60 and 70% of the heart rate reserve) and recovery (5 min). In the AR, the subjects remained cycling in the recovery phase at intensity between 30% and 35% of heart rate reserve, while in the PR, the subjects stopped the exercise after finishing the exercise phase. Blood pressure and heart rate were measured before and over the 30 min after the interventions. There were no differences for systolic and diastolic blood pressures, heart rate and rate pressure product between active and passive recovery sessions. Also, all heart rate variability parameters changed similarly after exercise with passive or active recovery sessions. In summary, exercise with active recovery does not affect the autonomic and haemodynamic responses after moderate-intensity aerobic exercise in healthy young male individuals. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

NOTE: Haemodynamic resistance model of monochorionic twin pregnancies complicated by acardiac twinning

NASA Astrophysics Data System (ADS)

Umur, Asli; van Gemert, Martin J. C.; van den Wijngaard, Jeroen P. H. M.; Ross, Michael G.; Nikkels, Peter G. J.

2004-07-01

An acardiac twin is a severely malformed monochorionic twin fetus that lacks most organs, particularly a heart. It grows during pregnancy, because it is perfused by its developmentally normal co-twin (called the pump twin) via a set of placental arterioarterial and venovenous anastomoses. The pump twin dies intrauterine or neonatally in about 50% of the cases due to congestive heart failure, polyhydramnios and prematurity. Because the pathophysiology of this pregnancy is currently incompletely understood, we modified our previous haemodynamic model of monochorionic twins connected by placental vascular anastomoses to include the analysis of acardiac twin pregnancies. We incorporated the fetoplacental circulation as a resistance circuit and used the fetal umbilical flow that perfuses the body to define fetal growth, rather than the placental flow as done previously. Using this modified model, we predicted that the pump twin has excess blood volume and increased mean arterial blood pressure compared to those in the acardiac twin. Placental perfusion of the acardiac twin is significantly reduced compared to normal, as a consequence of an increased venous pressure, possibly implying reduced acardiac placental growth. In conclusion, the haemodynamic analysis may contribute to an increased knowledge of the pathophysiologic consequences of an acardiac body mass for the pump twin.

Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

PubMed

Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

2016-06-01

Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

PubMed Central

Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

2016-01-01

Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

Anti-atherosclerotic and anti-inflammatory actions of sesame oil.

PubMed

Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry; Parthasarathy, Sampath

2015-01-01

Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(-/-)) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection.

PubMed

Bray, Natasha; Burrows, Fiona E; Jones, Myles; Berwick, Jason; Allan, Stuart M; Schiessl, Ingo

2016-08-24

Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation. We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1β or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1β (IL-1β). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a 'Clark-style' electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively. 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1β injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1β injection

Time course of haemodynamic, respiratory and inflammatory disturbances induced by experimental acute pulmonary polystyrene microembolism.

PubMed

Dolci, Daniel T; Fuentes, Carolina B; Rolim, Denise; Park, Marcelo; Schettino, Guilherme P P; Azevedo, Luciano C P

2010-01-01

The time course of cardiopulmonary alterations after pulmonary embolism has not been clearly demonstrated and nor has the role of systemic inflammation on the pathogenesis of the disease. This study aimed to evaluate over 12 h the effects of pulmonary embolism caused by polystyrene microspheres on the haemodynamics, lung mechanics and gas exchange and on interleukin-6 production. Ten large white pigs (weight 35-42 kg) had arterial and pulmonary catheters inserted and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter approximately 300 micromol l(-1)) until a value of pulmonary mean arterial pressure of twice the baseline was obtained. Five other animals received only saline. Haemodynamic and respiratory data and pressure-volume curves of the respiratory system were collected. A bronchoscopy was performed before and 12 h after embolism, when the animals were euthanized. The embolism group developed hypoxaemia that was not corrected with high oxygen fractions, as well as higher values of dead space, airway resistance and lower respiratory compliance levels. Acute haemodynamic alterations included pulmonary arterial hypertension with preserved systemic arterial pressure and cardiac index. These derangements persisted until the end of the experiments. The plasma interleukin-6 concentrations were similar in both groups; however, an increase in core temperature and a nonsignificant higher concentration of bronchoalveolar lavage proteins were found in the embolism group. Acute pulmonary embolism induced by polystyrene microspheres in pigs produces a 12-h lasting hypoxaemia and a high dead space associated with high airway resistance and low compliance. There were no plasma systemic markers of inflammation, but a higher central temperature and a trend towards higher bronchoalveolar lavage proteins were found.

Household air pollution and measures of blood pressure, arterial stiffness and central haemodynamics.

PubMed

Baumgartner, Jill; Carter, Ellison; Schauer, James J; Ezzati, Majid; Daskalopoulou, Stella S; Valois, Marie-France; Shan, Ming; Yang, Xudong

2018-02-09

We evaluated the exposure-response associations between personal exposure to air pollution from biomass stoves and multiple vascular and haemodynamic parameters in rural Chinese women. We analysed the baseline information from a longitudinal study in southwestern China. Women's brachial and central blood pressure and pulse pressure, carotid-femoral pulse wave velocity and augmentation index, and their 48-hour personal exposures to fine particulate matter (PM 2.5 ) and black carbon were measured in summer and winter. We evaluated the associations between exposure to air pollution and haemodynamic parameters using mixed-effects regression models adjusted for known cardiovascular risk factors. Women's (n=205, ages 27-86 years) exposures to PM 2.5 and black carbon ranged from 14 µg/m 3 to 1405 µg/m 3 and 0.1-121.8 µg/m 3 , respectively. Among women aged ≥50 years, increased PM 2.5 exposure was associated with higher systolic (brachial: 3.5 mm Hg (P=0.05); central: 4.4 mm Hg (P=0.005)) and diastolic blood pressure (central: 1.3 mm Hg (P=0.10)), higher pulse pressure (peripheral: 2.5 mm Hg (P=0.05); central: 2.9 mm Hg (P=0.008)) and lower peripheral-central pulse pressure amplification (-0.007 (P=0.04)). Among younger women, the associations were inconsistent in the direction of effect and not statistically significant. Increased PM 2.5 exposure was associated with no difference in pulse wave velocity and modestly higher augmentation index though the CI included zero (1.1%; 95% CI -0.2% to 2.4%). Similar associations were found for black carbon exposure. Exposure to household air pollution was associated with higher blood pressure and central haemodynamics in older Chinese women, with no associations observed with pulse wave velocity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

PubMed

Maggi, Paolo; Perilli, Francesco; Lillo, Antonio; Carito, Valentina; Epifani, Giuseppe; Bellacosa, Chiara; Pastore, Giuseppe; Regina, Guido

2007-02-01

We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

NASA Astrophysics Data System (ADS)

Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography

PubMed Central

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; de Melo, Enaldo Vieira; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; de Matos, Carlos José Oliveira; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-01-01

Background In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. Objective To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). Methods This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. Results The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. Conclusions The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers. PMID:29723329

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography.

PubMed

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; Melo, Enaldo Vieira de; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; Matos, Carlos José Oliveira de; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-05-03

In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers.

Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling

NASA Astrophysics Data System (ADS)

Dana, Nicholas; Sowers, Timothy; Karpiouk, Andrei; Vanderlaan, Donald; Emelianov, Stanislav

2017-10-01

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (<0.13). Dual-wavelength analysis proved promising, with 1210 nm as the most successful primary wavelength (≈1.0). Results suggest that, without flushing the luminal blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response.

PubMed

Brkovic, Bozidar M B; Savic, Miroslav; Andric, Miroslav; Jurisic, Milan; Todorovic, Ljubomir

2010-12-01

There is no data concerning the use of the intraseptal anaesthesia (ISA) for single tooth extraction. The aims of this study were to compare the clinical efficacy and haemodynamic responses of the ISA with the periodontal ligament anaesthesia (PLA) for single tooth extraction. Thirty-five randomly selected healthy patients (ASA I) undergoing maxillary lateral incisors extraction entered the study. Onset of anaesthesia, the width of the anaesthetic field and duration of anaesthesia were recorded by pinprick testing. Intensity of anaesthesia was evaluated on a visual analogue scale. Haemodynamic parameters were recorded simultaneously at different time points after anaesthesia injection. The two techniques of local anaesthesia did not show statistically significant differences regarding the success rate and onset of anaesthesia, while the duration of the ISA on the buccal site was significantly longer in comparison with the PLA. The intensity of the achieved anaesthesia, estimated by the experienced pain during procedure, pointed out that pain was recorded in 24% of cases in the ISA group, and in 19% in the PLA group without significant differences. Postoperative pain was found to be smaller in the ISA group (70.9% of treated sites) than in the PLA group (81.3% of treated sites); however, this difference was not significant. Although the heart rate increased in both groups, there were no significant differences in the patients' haemodynamic response between the ISA and the PLA. The results of the present study indicate that both techniques are useful and suitable for the routine tooth extraction.

Advances in non-invasive drug delivery for atherosclerotic heart disease.

PubMed

Maranhão, Raul C; Tavares, Elaine R

2015-07-01

Apart from statins, anti-platelet agents and invasive procedures, the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is scarce and only partially protects CHD patients from major adverse cardiac events. Several novel non-invasive strategies are being developed to widen the therapeutic options. Among them, drug delivery tools were tested in vivo encompassing liposomes, micelles, polymeric, metallic and lipid nanoparticles used as carriers of statins, corticosteroids, a bisphosphonate, a glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a compound of traditional Chinese medicine. All preparations improved parameters related to atherosclerotic lesions induced in rabbits, rats and mice and reduced neointima formation in experiments aiming to prevent post-stenting restenosis. In subjects submitted to percutaneous coronary intervention, nanoparticle formulations of paclitaxel and alendronate showed safety but are still not conclusive regarding in-stent late loss. The experience of our group in atherosclerotic rabbits treated with non-protein lipid nanoparticles associated with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is summarized, and preliminary safety data in CHD patients are anticipated. Taken together, these studies show that non-invasive drug-delivery systems may become promising tools to rescue CHD patients from the risks of severe and life-threatening lesions that should be more energetically treated.

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

PubMed

Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-09-01

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

PubMed Central

Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

Haemodynamic responses in chronically painful, human trapezius muscle to cold pressor stimulation.

PubMed

Acero, C O; Kuboki, T; Maekawa, K; Yamashita, A; Clark, G T

1999-10-01

The aim was to compare haemodynamic responses in trapezius muscles to cold pressor stimulation in individuals with localized trapezius myalgia and asymptomatic controls. Nine males with chronic localized pain in the trapezius (mean age, 23.2 years) and nine male controls (mean age, 24.6 years) who had no medical history of migraine, hypertension or sustained pain in the trapezius region were investigated. Two experimental (cold pressor and mock) trials were performed in a randomly assigned sequence. In the cold pressor trial the participant's left foot and ankle were immersed in 4 degrees C cold water for 2 min; the mock trial was done without that stimulus. Blood volume was continuously recorded 1 min before, 2 min during, and 5 min after cold pressor stimulation using near-infrared spectroscopy. Each participant's blood-volume data were baseline-corrected and submitted to statistical analysis. Results showed that the individuals with muscle pain exhibited a significantly lower mean blood volume than the controls during cold pressor stimulation (p = 0.0367). Upon withdrawal of that stimulation, the mean blood volume in both groups fell below the baseline. These results suggest that individuals with chronic regional trapezius myalgia have less capacity to vasodilate this muscle during cold pressor stimulation than those without such myalgia. It is not yet known if this difference in the haemodynamic response is a cause or an effect of the myalgia.

Haemodynamic responses and changes of haemostatic risk factors in cold-adapted humans.

PubMed

De Lorenzo, F; Kadziola, Z; Mukherjee, M; Saba, N; Kakkar, V V

1999-09-01

Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p < 0.001), and plasma viscosity (-3.0 s; p < 0.001), and a mild but significant increase in PAI-1 (+0.3 IU/ml; p = 0.02). The pressure rate product (systolic blood pressure x heart rate) was also significantly lower after cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

PubMed

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

PubMed Central

Keyamura, Yuka; Nagano, Chifumi; Kohashi, Masayuki; Niimi, Manabu; Nozako, Masanori; Koyama, Takashi; Yasufuku, Reiko; Imaizumi, Ayako; Itabe, Hiroyuki; Yoshikawa, Tomohiro

2014-01-01

Objective Lowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin. Methods and Results Atherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo. Conclusions Probucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis. PMID:24810608

Reflexology has no immediate haemodynamic effect in patients with chronic heart failure: a double blind randomised controlled trial.

PubMed

Jones, Jenny; Thomson, Patricia; Lauder, William; Howie, Kate; Leslie, Stephen J

2013-08-01

This study measured the effects of reflexology in 12 reflexology-naive patients with chronic heart failure in a placebo-controlled, double blind randomised controlled study design. Outcomes included 'beat-to-beat' non-invasive continuous measurement of cardiovascular parameters and measurement of state of anxiety and pain/discomfort. There were no changes in any of the haemodynamic parameters measured (all p > 0.05). Perceived state of anxiety was significantly reduced post treatment in the control group only (p = 0.03). Reflexology applied to the feet of patients with chronic heart failure appears to have no immediate haemodynamic effects. While any long term treatment effect is uncertain, it would appear that reflexology is safe for use in this patient group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

PubMed

Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

2007-01-01

To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

Large Artery Atherosclerotic Occlusive Disease.

PubMed

Cole, John W

2017-02-01

Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient's symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient's history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and death should be carefully considered.

Effect-site concentration of remifentanil required to blunt haemodynamic responses during tracheal intubation: A randomized comparison between single- and double-lumen tubes.

PubMed

Kim, Tae Kyong; Hong, Deok Man; Lee, Seo Hee; Paik, Hyesun; Min, Se Hee; Seo, Jeong-Hwa; Jung, Chul-Woo; Bahk, Jae-Hyon

2018-01-01

Objective To investigate the effect-site concentration of remifentanil required to blunt haemodynamic responses during tracheal intubation with a single-lumen tube (SLT) or a double-lumen tube (DLT). Methods Patients scheduled for thoracic surgery requiring one-lung ventilation were randomly allocated to either the SLT or DLT group. All patients received a target-controlled infusion of propofol and a predetermined concentration of remifentanil. Haemodynamic parameters during intubation were recorded. The effect-site concentration of remifentanil was determined using a delayed up-and-down sequential allocation method. Results A total of 92 patients were enrolled in the study. The effective effect-site concentrations of remifentanil required to blunt haemodynamic responses in 50% of patients (EC 50 ) estimated by isotonic regression with bootstrapping was higher in the DLT than the SLT group (8.5 ng/ml [95% confidence interval (CI) 8.0-9.5 ng/ml] versus 6.5 ng/ml [95% CI 5.6-6.7 ng/ml], respectively). Similarly, the effective effect-site concentrations of remifentanil in 95% of patients in the DLT group was higher than the SLT group (9.9 ng/ml [95% CI 9.8-10.0 ng/ml] versus 7.0 ng/ml [95% CI 6.9-7.0 ng/ml], respectively). Conclusions This study demonstrated that a DLT requires a 30% higher EC 50 of remifentanil than does an SLT to blunt haemodynamic responses during tracheal intubation when combined with a target-controlled infusion of propofol. Trial registration Clinicaltrials.gov identifier: NCT01542099.

Immediate central and peripheral haemodynamic effects of a new vasodilating agent Pinacidil (P1134) in hypertensive man.

PubMed

Carlsen, J E; Kardel, T; Hilden, T; Tangø, M; Trap-Jensen, J

1981-08-01

The purpose of this study was to evaluate the immediate central and peripheral haemodynamic effects of a new vasodilating agent P 1134, in hypertensive man. After oral administration of 25 mg P 1134, the maximal haemodynamic changes were (mean +/- 1 SEM): mean blood pressure fell from 121.8 +/- 6.5 to 80.5 +/- 7.8 mmHg, heart rate increased 24.2 +/- 4.5 beats/min, cardiac output rose 2.9 +/- 0.3 1/min and forearm blood flow increased 1.0 +/- 0.1 ml/100 ml tissue/min. Stroke volume increased 17.0 +/- 2.1 ml and the inotropic state of the heart as judged from systolic time intervals increased. Total peripheral resistance and forearm vascular resistance were both reduced by approx. 50%. Linear correlations were found between the serum concentration of P 1134 and the change in mean blood pressure and total peripheral resistance. Changes in the other parameters mentioned above occurred progressively with changes in mean blood pressure and total peripheral resistance. It can be concluded that P 1134 is a very potent hypotensive agent with a haemodynamic profile identical to that seen with vasodilators with preferably act on precapillary resistance vessels. Potency and maximal efficacy exceeds that of hydralazine and seems like that of minoxidil. P 1134 is remarkably free from side-effects apart from causing water retention as all other vasodilators. It can be administered orally as well as intravenously. This makes P 1134 a very interesting compound in the treatment of moderate to severe hypertension, and further studies are well-founded.

Quantification of carotid atherosclerotic plaque components using feature space analysis and magnetic resonance imaging.

PubMed

Karmonik, Christof; Basto, Pamela; Morrisett, Joel D

2006-01-01

Atherosclerosis is one of the main causes of cardiovascular disease, accounting for more than one third of all deaths in the United States, there is a growing need to develop non-invasive techniques to assess the severity of atherosclerotic plaque burden. Recent research has suggested that not the size of the atherosclerotic plaque but rather its composition is indicative for plaque rupture as the underlying event of stroke and acute coronary syndrome. With its excellent soft-tissue contrast, magnetic resonance imaging (MRI) is a favored modality for examining plaque composition. In an ex-vivo study, aimed to show the feasibility of quantifying the components of carotid atherosclerotic plaques in-vivo, we acquired multi-contrast MRI images of 13 freshly excised endarterectomy tissues with commercially available MRI sequences and a human surface coil. Feature space analysis (FSA) was utilized in four representative tissues to determine the total relative abundance of calcific, lipidic, fibrotic, thrombotic and normal components as well as in consecutive 2 mm sections across the carotid bifurcation in each tissue. Excellent qualitative agreement between the FSA results and the results obtained from histological methods was observed. This study demonstrates the feasibility of combining MRI with FSA to quantify carotid atherosclerotic plaques in-vivo.

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Quantitative evaluation of lipid concentration in atherosclerotic plaque phantom by near-infrared multispectral angioscope at wavelengths around 1200 nm

NASA Astrophysics Data System (ADS)

Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

2015-07-01

Atherosclerosis is a primary cause of critical ischemic diseases like heart infarction or stroke. A method that can provide detailed information about the stability of atherosclerotic plaques is required. We focused on spectroscopic techniques that could evaluate the chemical composition of lipid in plaques. A novel angioscope using multispectral imaging at wavelengths around 1200 nm for quantitative evaluation of atherosclerotic plaques was developed. The angioscope consists of a halogen lamp, an indium gallium arsenide (InGaAs) camera, 3 optical band pass filters transmitting wavelengths of 1150, 1200, and 1300 nm, an image fiber having 0.7 mm outer diameter, and an irradiation fiber which consists of 7 multimode fibers. Atherosclerotic plaque phantoms with 100, 60, 20 vol.% of lipid were prepared and measured by the multispectral angioscope. The acquired datasets were processed by spectral angle mapper (SAM) method. As a result, simulated plaque areas in atherosclerotic plaque phantoms that could not be detected by an angioscopic visible image could be clearly enhanced. In addition, quantitative evaluation of atherosclerotic plaque phantoms based on the lipid volume fractions was performed up to 20 vol.%. These results show the potential of a multispectral angioscope at wavelengths around 1200 nm for quantitative evaluation of the stability of atherosclerotic plaques.

Fluid-phase pinocytosis of LDL by macrophages: a novel target to reduce macrophage cholesterol accumulation in atherosclerotic lesions.

PubMed

Kruth, Howar S

2013-01-01

Circulating low-density lipoprotein (LDL) that enters the blood vessel wall is the main source of cholesterol that accumulates within atherosclerotic plaques. Much of the deposited cholesterol accumulates within plaque macrophages converting these macrophages into cholesterol-rich foamy looking cells. Cholesterol accumulation in macrophages contributes to cholesterol retention within the vessel wall, and promotes vessel wall inflammation and thrombogenicity. Thus, how macrophages accumulate cholesterol and become foam cells has been the subject of intense investigation. It is generally believed that macrophages accumulate cholesterol only through scavenger receptor-mediated uptake of modified LDL. However, an alternative mechanism for macrophage foam cell formation that does not depend on LDL modification or macrophage receptors has been elucidated. By this alternative mechanism, macrophages show receptor-independent uptake of unmodified native LDL that is mediated by fluid-phase pinocytosis. In receptor-independent, fluid-phase pinocytosis, macrophages take up LDL as part of the fluid that they ingest during micropinocytosis within small vesicles called micropinosomes, and by macropinocytosis within larger vacuoles called macropinosomes. This produces cholesterol accumulation in macrophages to levels characteristic of macrophage foam cells in atherosclerotic plaques. Fluid-phase pinocytosis of LDL is a plausible mechanism that can explain how macrophages accumulate cholesterol and become disease-causing foam cells. Fluid-phase pinocytosis of LDL is a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. Recent studies show that phosphoinositide 3-kinase (PI3K), liver X receptors (LXRs), the macrophage colony-stimulating factor (M-CSF) receptor, and protein kinase C (PKC) mediate macrophage macropinocytosis of LDL, and thus, these may be relevant targets to inhibit macrophage cholesterol accumulation in atherosclerosis.

Anti-atherosclerotic effect of Fermentum Rubrum and Gynostemma pentaphyllum mixture in high-fat emulsion- and vitamin D3-induced atherosclerotic rats.

PubMed

Gou, San-Hu; Liu, Bei-Jun; Han, Xiu-Feng; Wang, Li; Zhong, Chao; Liang, Shan; Liu, Hui; Qiang, Yin; Zhang, Yun; Ni, Jing-Man

2018-05-01

The mixture of Hongqu and gypenosides (HG) is composed of Fermentum Rubrum (Hongqu, in Chinese) and total saponins of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, in Chinese) in a 3.6:1 weight ratio. Both Hongqu and Jiaogulan are considered valuable traditional Chinese medicines (TCMs); they have been commonly used in China for the treatment of hyperlipidemia and related diseases for centuries. The aim of the current study was assess the anti-atherosclerotic effect of HG. Sixty-four Wistar rats were randomly divided into eight groups: normal, model, positive control (simvastatin, 1 mg/kg), Hongqu-treated (72 mg/kg), gypenoside (total saponin)-treated (20 mg/kg), and three doses HG-treated (50, 100, and 200 mg/kg). All of the rats were fed a basal diet. Additionally, the model group rats were intragastrically administered a high-fat emulsion and intraperitoneally injected with vitamin D 3 . The serum lipid profiles, oxidative stress, inflammatory cytokine, and hepatic antioxidant levels were then determined. Furthermore, the liver histopathology and arterial tissue were analyzed, and the expression of hyperlipidemia- and atherosclerosis (AS)-related genes was measured using reverse transcription-polymerase chain reaction. The AS rat model was established after 80 days. Compared to the model group, the HG-treated groups showed an obvious improvement in the serum lipid profiles, oxidative stress, and inflammatory cytokine levels, and showed markedly increased hepatic total antioxidant capacity. Moreover, the expression of genes related to lipid synthesis and inflammation reduced and that of the genes related to lipid oxidation increased in the liver and arterial tissue, which also reflected an improved health condition. the anti-atherosclerotic effects of HG were superior to those of simvastatin, Hongqu, and the gypenosides. Therefore, HG may be a useful anti-atherosclerotic TCM preparation. Copyright © 2017. Published by Elsevier Taiwan LLC.

2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population.

PubMed

Cheung, B My; Cheng, C H; Lau, C P; Wong, C Ky; Ma, R Cw; Chu, D Ws; Ho, D Hk; Lee, K Lf; Tse, H F; Wong, A Sp; Yan, B Py; Yan, V Wt

2017-04-01

In Hong Kong, the prevalence of atherosclerotic cardiovascular disease has increased markedly over the past few decades, and further increases are expected. In 2008, the Hong Kong Cardiovascular Task Force released a consensus statement on preventing cardiovascular disease in the Hong Kong population. The present article provides an update on these recommendations. A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force-10 cardiologists, an endocrinologist, and a family physician-met in September 2014 and June 2015 in Hong Kong. Guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure were reviewed. Group members reviewed the 2008 Consensus Statement and relevant international guidelines. At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines. A final recommendation on each topic was generated by consensus after discussion. It is recommended that a formal risk scoring system should be used for risk assessment of all adults aged 40 years or older who have at least one cardiovascular risk factor. Individuals can be classified as having a low, moderate, or high risk of developing atherosclerotic cardiovascular disease, and appropriate interventions selected accordingly. Recommended lifestyle modifications include adopting a healthy eating pattern; maintaining a low body mass index; quitting smoking; and undertaking regular, moderate-intensity physical activity. Pharmacological interventions should be selected as appropriate after lifestyle modification.

In-line pressure-flow module for in vitro modelling of haemodynamics and biosensor validation

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Schaub, J. D.; Ewert, D. L.; Swope, R. D.; Convertino, V. A. (Principal Investigator)

1997-01-01

An in-line pressure-flow module for in vitro modelling of haemodynamics and biosensor validation has been developed. Studies show that good accuracy can be achieved in the measurement of pressure and of flow, in steady and pulstile flow systems. The model can be used for development, testing and evaluation of cardiovascular-mechanical-electrical anlogue models, cardiovascular prosthetics (i.e. valves, vascular grafts) and pressure and flow biosensors.

Comparison of the effects of antihypertensive treatment with angiotensin II blockade and beta-blockade on carotid wall structure and haemodynamics: protocol and baseline demographics.

PubMed

Ariff, Ben; Stanton, Alice; Barratt, Dean; Augst, Alex; Glor, Fadi; Poulter, Neil; Sever, Peter; Xu, Yun; Hughes, Alun; Thom, Simon A Mc G

2002-06-01

Several systemic factors have been shown to contribute to the acceleration of large vessel atheroma. Correction of these factors leads to a reduction in the progression of plaque formation and associated arterial wall thickness. Atheroma remains, however, a focal disease, developing at characteristic sites within the arterial tree. These sites are typically at areas of vessel branching or marked curvature, and correspond to regions of high tensile stress and low sheer stress, leading to the hypothesis that local haemodynamic factors and vessel wall mechanics potentiate the focal development of atheroma. Current assessment of vascular haemodynamics suffers from an inability to handle complex flow, and does not allow accurate determination of locally varying flow, and shear stress patterns. The application of computational fluid dynamic (CFD) flow simulation techniques to ultrasound and local pressure data, however, allows a comprehensive, non-invasive appraisal of haemodynamic flow parameters to be performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint Trial (CACHET) study compares the effects of two antihypertensive regimens, one b-blocker-based, the other angiotensin receptor blocker based, on carotid intima-media thickness. The collection of ultrasound and pressure data on each subject provides a unique opportunity to apply these data to the CFD model to study the effects of these antihypertensive regimens on local fluid dynamics. This will lead to a greater understanding of the relationship of these factors to atheroma formation and regression.

Large Artery Atherosclerotic Occlusive Disease

PubMed Central

Cole, John W.

2017-01-01

ABSTRACT Purpose of Review: Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient’s symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient’s history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Recent Findings: Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Summary: Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and

T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment

PubMed Central

Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann

2016-01-01

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

NASA Astrophysics Data System (ADS)

Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

2016-02-01

Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

[Comprehensive monitoring of cerebral haemodynamics during surgical interventions on brachiocephalic arteries].

PubMed

Ignat'ev, I M; Bredikhin, R A; Falina, T G; Vinogradova, V V; Khismatullina, L I

2010-01-01

The authors analysed a total of 152 surgical interventions on the brachiocephalic arteries (BCAs) performed in 142 patients. All the patients were subjected to intraoperative monitoring of cerebral haemodynamics by means of transcranial Doppler (TCD) ultrasonography simultaneously accompanied by electroencephalography (EEG). Additionally, the state of the reconstructed carotid arteries was controlled by means of ultrasonographic duplex scanning (USDS). Comparing the findings of the TCD recording and EEG made it possible to single out 5 groups of the operated patients. The EEG technique turned out to have more informative value as compared with TCD ultrasonography in determining the degree of cerebral ischaemia during clamping of the carotid arteries (CAs). Nine (5.9%) patients demonstrated lower tolerance of the brain to ischaemia, and the operation on the BCA was performed with the use of a temporal intraluminal bypass graft. Microembolic signals (MES) were registered in 54.6% of cases. Single MES were detected in six patients, sporadic MES--in 53, and multiple MES--in 24. Mention should be made that the--MES associated with the placement of the bypass graft appeared to be multiple and were registered in all the operated patients. Diffusion-weighted magnetic resonance tomography revealed fresh foci of lacunar cerebral infarctions in 14 (25%) of the 56 patients thus examined. Intraoperative USDS of the reconstructed carotid arteries revealed floatation of the residual remnants of the intima in two patients, which was the cause of a repeat intervention. Combined monitoring of cerebral haemodynamics makes it possible to timely prevent cerebral ischaemia, to narrow the indications for placement of an intraluminal bypass graft, and to dramatically decrease the rate of postoperative complications.

A Salmon Protein Hydrolysate Exerts Lipid-Independent Anti-Atherosclerotic Activity in ApoE-Deficient Mice

PubMed Central

Busnelli, Marco; Bjørndal, Bodil; Holm, Sverre; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S.; Dellera, Federica; Halvorsen, Bente; Aukrust, Pål; Sirtori, Cesare R.; Nordrehaug, Jan E.; Skorve, Jon; Berge, Rolf K.; Chiesa, Giulia

2014-01-01

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E−/− mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE−/− mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20∶4n-6) and oleic acid (C18∶1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE−/− mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids. PMID:24840793

What is the normal haemodynamic response to passive leg raise? A study of healthy volunteers.

PubMed

Elwan, Mohammed H; Roshdy, Ashraf; Reynolds, Joseph A; Elsharkawy, Eman M; Eltahan, Salah M; Coats, Timothy J

2018-05-04

Passive leg raise (PLR) is used as self-fluid challenge to optimise fluid therapy by predicting preload responsiveness. However, there remains uncertainty around the normal haemodynamic response to PLR with resulting difficulties in application and interpretation in emergency care. We aim to define the haemodynamic responses to PLR in spontaneously breathing volunteers using a non-invasive cardiac output monitor, thoracic electrical bioimpedance, TEB (PLR-TEB). We recruited healthy volunteers aged 18 or above. Subjects were monitored using TEB in a semirecumbent position, followed by PLR for 3 min. The procedure was repeated after 6 min at the starting position. Correlation between the two PLRs was assessed using Spearman's r (r s ). Agreement between the two PLRs was evaluated using Cohen Kappa with responsiveness defined as ≥10% increase in stroke volume. Parametric and non-parametric tests were used as appropriate to evaluate statistical significance of baseline variables between responders and non-responders. We enrolled 50 volunteers, all haemodynamically stable at baseline, of whom 49 completed the study procedure. About half of our subjects were preload responsive. The ∆SV in the two PLRs was correlated (r s =0.68, 95% CI 0.49 to 0.8) with 85% positive concordance. Good agreement was observed with Cohen Kappa of 0.67 (95% CI 0.45 to 0.88). Responders were older and had significantly lower baseline stroke volume and cardiac output. Our results suggest that the PLR-TEB is a feasible method in spontaneously breathing volunteers with reasonable reproducibility. The age and baseline stroke volume effect suggests a more complex underlying physiology than commonly appreciated. The fact that half of the volunteers had a positive preload response, against the 10% threshold, leads to questions about how this measurement should be used in emergency care and will help shape future patient studies. © Article author(s) (or their employer(s) unless otherwise

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.

PubMed

Luo, Yuemei; Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

2016-01-01

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

Selective removal of cholesterol ester in atherosclerotic plaque using nanosecond pulsed laser at 5.75 μm

NASA Astrophysics Data System (ADS)

Ishii, K.; Tsukimoto, H.; Hazama, H.; Awazu, K.

2008-02-01

Laser angioplasty, for example XeCl excimer laser angioplasty, has gained more attention in addition to conventional methods of surgical and interventional treatment of atherosclerotic diseases such as bypass operation and balloon dilatation. Low degrees of thermal damage after ablation of atherosclerotic lesions have been achieved by XeCl excimer laser at 308 nm. However, in most cases, laser ablation is not selective and normal arterial wall is also damaged. To avoid complications such as severe dissections or perforation of the arterial wall in an angioplasty, a laser light source with high ablation efficiency but low arterial wall injury is desirable. At atherosclerotic lesions, cholesterol accumulates on the tunica intima by establishing an ester bond with fatty acids such as oleic acid, and thus cholesterol ester is the main component of atherosclerotic plaques. Mid-infrared pulsed laser at 5.75 μm is selectively well absorbed in C=O stretching vibration mode of ester bonds. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 μm irradiation of cholesterol ester in atherosclerotic plaques. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference frequency generation method, with a wavelength of 5.75 μm, a pulse width of 5 nsec and a pulse duration of 10 Hz. It was confirmed that non-invasive interaction to normal thoracic aortas could be induce by the parameters, the wavelength of 5.75 μm, the average power densities of 35 W/cm2 and the irradiation time under 10 sec. This study shows that nanosecond pulsed laser irradiations at 5.75 μm provide an alternative laser light source as an effectively cutting, less traumatic tool for removal of atherosclerotic plaque.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

PubMed

Yatera, Kazuhiro; Hsieh, Joanne; Hogg, James C; Tranfield, Erin; Suzuki, Hisashi; Shih, Chih-Horng; Behzad, Ali R; Vincent, Renaud; van Eeden, Stephan F

2008-02-01

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

Medical therapy is best for atherosclerotic renal artery stenosis: Arguments for.

PubMed

Annigeri, R A

2012-01-01

Atherosclerotic renal artery stenosis (ARAS) is a common condition that causes hypertension and reduction in the glomerular filtration rate and is an independent risk factor for death. Despite high technical success, the clinical benefit of renal artery (RA) angioplasty with stenting in ARAS remains doubtful. The published randomized clinical trials provide no support for the notion that renal angioplasty with stenting significantly improves blood pressure, preserves renal function, or reduces episodes of congestive heart failure in patients with ARAS. RA stenting is associated with procedure-related morbidity and mortality. Agents to block the renin-angiotensin-aldosterone system improve outcome and should be a part of a multifaceted medical regimen in ARAS. Medical therapy effectively controls atherosclerotic renovascular disease at all levels of vasculature and hence is the best therapy for ARAS.

Identification of Atherosclerotic Plaques in Carotid Artery by Fluorescence Spectroscopy

NASA Astrophysics Data System (ADS)

Rocha, Rick; Villaverde, Antonio Balbin; Silveira, Landulfo; Costa, Maricília Silva; Alves, Leandro Procópio; Pasqualucci, Carlos Augusto; Brugnera, Aldo

2008-04-01

The aim of this work was to identify the presence of atherosclerotic plaques in carotid artery using the Fluorescence Spectroscopy. The most important pathogeny in the cardiovascular disorders is the atherosclerosis, which may affect even younger individuals. With approximately 1.2 million heart attacks and 750,000 strokes afflicting an aging American population each year, cardiovascular disease remains the number one cause of death. Carotid artery samples were obtained from the Autopsy Service at the University of São Paulo (São Paulo, SP, Brazil) taken from cadavers. After a histopathological analysis the 60 carotid artery samples were divided into two groups: normal (26) and atherosclerotic plaques (34). Samples were irradiated with the wavelength of 488 nm from an Argon laser. A 600 μm core optical fiber, coupled to the Argon laser, was used for excitation of the sample, whereas another 600 optical fiber, coupled to the spectrograph entrance slit, was used for collecting the fluorescence from the sample. Measurements were taken at different points on each sample and then averaged. Fluorescence spectra showed a single broad line centered at 549 nm. The fluorescence intensity for each sample was calculated by subtracting the intensity at the peak (550 nm) and at the bottom (510 nm) and then data were statistically analyzed, looking for differences between both groups of samples. ANOVA statistical test showed a significant difference (p<0,05) between both types of tissues, with regard to the fluorescence peak intensities. Our results indicate that this technique could be used to detect the presence of the atherosclerotic in carotid tissue.

A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

Smith, Michael S. D.; Ko, Alex C. T.; Ridsdale, Andrew; Schattka, Bernie; Pegoraro, Adrian; Hewko, Mark D.; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

2009-06-01

In this study we compare the single-photon autofluorescence and multi-photon emission spectra obtained from the luminal surface of healthy segments of artery with segments where there are early atherosclerotic lesions. Arterial tissue was harvested from atherosclerosis-prone WHHL-MI rabbits (Watanabe heritable hyperlipidemic rabbit-myocardial infarction), an animal model which mimics spontaneous myocardial infarction in humans. Single photon fluorescence emission spectra of samples were acquired using a simple spectrofluorometer set-up with 400 nm excitation. Samples were also investigated using a home built multi-photon microscope based on a Ti:sapphire femto-second oscillator. The excitation wavelength was set at 800 nm with a ~100 femto-second pulse width. Epi-multi-photon spectroscopic signals were collected through a fibre-optics coupled spectrometer. While the single-photon fluorescence spectra of atherosclerotic lesions show minimal spectroscopic difference from those of healthy arterial tissue, the multi-photon spectra collected from atherosclerotic lesions show marked changes in the relative intensity of two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals when compared with those from healthy arterial tissue. The observed sharp increase of the relative SHG signal intensity in a plaque is in agreement with the known pathology of early lesions which have increased collagen content.

Mechanical properties of human atherosclerotic intima tissue.

PubMed

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stenting and medical therapy for atherosclerotic renal-artery stenosis.

PubMed

Cooper, Christopher J; Murphy, Timothy P; Cutlip, Donald E; Jamerson, Kenneth; Henrich, William; Reid, Diane M; Cohen, David J; Matsumoto, Alan H; Steffes, Michael; Jaff, Michael R; Prince, Martin R; Lewis, Eldrin F; Tuttle, Katherine R; Shapiro, Joseph I; Rundback, John H; Massaro, Joseph M; D'Agostino, Ralph B; Dworkin, Lance D

2014-01-02

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

PubMed

Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

2016-01-01

Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.

PubMed

Zhou, Boda; Zu, Lingyun; Chen, Yong; Zheng, Xilong; Wang, Yuhui; Pan, Bing; Dong, Min; Zhou, Enchen; Zhao, Mingming; Zhang, Youyi; Zheng, Lemin; Gao, Wei

2017-01-10

High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO 2 -oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects. Here we determined the effects of NO 2 -oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model. Our results showed that native HDL promoted SMC proliferation and migration, whereas NO 2 -oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO 2 -oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO 2 -oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO 2 -oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO 2 -oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque. These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI.

Overexpression of TGF-ß1 in Macrophages Reduces and Stabilizes Atherosclerotic Plaques in ApoE-Deficient Mice

PubMed Central

Orning, Carolin; Crain, Jeanine; Küpper, Ines; Wiese, Elena; Protschka, Martina; Blessing, Manfred; Lackner, Karl J.; Torzewski, Michael

2012-01-01

Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE−/− mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. PMID:22829904

Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saba, Luca, E-mail: lucasaba@tiscali.i; Potters, Fons; Lugt, Aad van der

2010-08-15

In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parametersmore » must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.« less

Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography.

PubMed

Yun, Chun-Ho; Schlett, Christopher L; Rogers, Ian S; Truong, Quynh A; Toepker, Michael; Donnelly, Patrick; Brady, Thomas J; Hoffmann, Udo; Bamberg, Fabian

2009-08-01

The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP

Endovascular revascularization for aortoiliac atherosclerotic disease

PubMed Central

Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

2016-01-01

Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry.

PubMed

Hansmeier, Nicole; Buttigieg, Josef; Kumar, Pankaj; Pelle, Shaneen; Choi, Kyoo Yoon; Kopriva, David; Chao, Tzu-Chiao

2018-01-05

Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.

Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

NASA Astrophysics Data System (ADS)

Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

2017-01-01

Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis.

PubMed

Patel, Chirag Ramanlal; Engineer, Smita R; Shah, Bharat J; Madhu, S

2012-11-01

Dexmedetomidine, an α2 agonist, when used as an adjuvant in general anaesthesia attenuates stress response to various noxious stimuli, maintains perioperative haemodynamic stability and provides sedation without significant respiratory depression postoperatively. Sixty patients were randomly divided into two groups of 30 each. In group A, fentanyl 2 μg/kg and in group B dexmedetomidine were given intravenously as loading dose of 1 μg/kg over 10 min prior to induction. After induction with thiopentone, in group B, dexmedetomidine was given as infusion at a dose of 0.2-0.8 μg/kg. Sevoflurane was used as inhalation agent in both groups. Haemodynamic variables and entropy (response entropy and state entropy) were recorded continuously. Postoperative sedation and recovery were assessed by sedation score and modified Aldrete's score, respectively. Dexmedetomidine significantly attenuates stress response at intubation with lesser increase in heart rate (10% vs. 17%), systolic blood pressure (6% vs. 23%) and diastolic blood pressure (7% vs. 20%) as compared to the control group (P<0.05). Intraoperatively, an average of 8% fall in systolic blood pressure and 8.16% fall in diastolic pressure in the test group as compared to 3.6% rise in systolic and 3.3% in diastolic pressure of the control group was observed. Postoperatively, the test group showed significant sedation at 2 h as compared to the control group (P=0.00) and recovery was better in the control group for the first 2 h post extubation. Dexmedetomidine attenuates various stress responses during surgery and maintains the haemodynamic stability when used as an adjuvant in general anaesthesia. Also, the sedative action of dexmedetomidine delays recovery for the first few hours post extubation.

The haemodynamic effects of bolus versus slower infusion of intravenous crystalloid in healthy volunteers.

PubMed

Ukor, Ida F; Hilton, Andrew K; Bailey, Michael J; Bellomo, Rinaldo

2017-10-01

This pilot study aimed to characterise the haemodynamic effect of 1L of IV normal saline (NS) administered as a rapid versus slow infusion on cardiac output (CO), heart rate (HR), systemic blood pressures, and carotid blood flow in six healthy volunteers. Six healthy male volunteers aged 18-65years were randomized to receive 1L NS given over 30min or 120min. On a subsequent study session the alternate fluid regimen was administered. Haemodynamic data was gathered using a non-invasive finger arterial pressure monitor (Nexfin®), echocardiography and carotid duplex sonography. Time to micturition and urine volume was also assessed. Compared to baseline, rapid infusion of 1L of saline over 30min produced a fall in Nexfin®-measured CO by 0.62L/min (p<0.001), whereas there was a marginal but significant increase during infusion of 1L NS over 120min of 0.02L/min (p<0.001). This effect was mirrored by changes in HR and blood pressure (BP) (p<0.001). There were no significant changes in carotid blood flow, time to micturition, or urine volume produced. Slower infusion of 1L NS in healthy male volunteers produced a greater increase in CO, HR and BP than rapid infusion. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches

PubMed Central

Ma, Ying; Shaik, Mohammed A.; Kozberg, Mariel G.; Thibodeaux, David N.; Zhao, Hanzhi T.; Yu, Hang

2016-01-01

Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574312

What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for Atherosclerotic Plaque Regression.

PubMed

Biondi-Zoccai, Giuseppe; Mastrangeli, Simona; Romagnoli, Enrico; Peruzzi, Mariangela; Frati, Giacomo; Roever, Leonardo; Giordano, Arturo

2018-01-17

Atherosclerosis has major morbidity and mortality implications globally. While it has often been considered an irreversible degenerative process, recent evidence provides compelling proof that atherosclerosis can be reversed. Plaque regression is however difficult to appraise and quantify, with competing diagnostic methods available. Given the potential of evidence synthesis to provide clinical guidance, we aimed to review recent meta-analyses on diagnostic methods for atherosclerotic plaque regression. We identified 8 meta-analyses published between 2015 and 2017, including 79 studies and 14,442 patients, followed for a median of 12 months. They reported on atherosclerotic plaque regression appraised with carotid duplex ultrasound, coronary computed tomography, carotid magnetic resonance, coronary intravascular ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses showed significant atherosclerotic plaque regression with lipid-lowering therapy, with the most notable effects on echogenicity, lipid-rich necrotic core volume, wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant interactions were found with concomitant changes in low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels, and with ethnicity. Atherosclerotic plaque regression and conversion to a stable phenotype is possible with intensive medical therapy and can be demonstrated in patients using a variety of non-invasive and invasive imaging modalities.

Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro

PubMed Central

Lanter, Bernard B.

2015-01-01

In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. PMID:26216428

Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro.

PubMed

Lanter, Bernard B; Davies, David G

2015-10-01

In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report.

PubMed

Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min; Tanaka, Satona; Higashikubo, Ryuji; Gauthier, Jason M; Sultan, Deborah; Lavine, Kory J; Brody, Steven L; Gelman, Andrew E; Gropler, Robert J; Liu, Yongjian; Kreisel, Daniel

2018-05-01

Aortic arch transplants have advanced our understanding of processes that contribute to progression and regression of atherosclerotic plaques. To characterize the dynamic behavior of monocytes and macrophages in atherosclerotic plaques over time, we developed a new model of cervical aortic arch transplantation in mice that is amenable to intravital imaging. Vascularized aortic arch grafts were transplanted heterotropically to the right carotid arteries of recipient mice using microsurgical suture techniques. To image immune cells in atherosclerotic lesions during regression, plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted into syngeneic CX 3 CR1 GFP reporter mice. Grafts were evaluated histologically, and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were imaged intravitally by 2-photon microscopy in serial fashion. In complementary experiments, CCR2 + cells in plaques were serially imaged by positron emission tomography using specific molecular probes. Plaques in ApoE-deficient grafts underwent regression after transplantation into normolipidemic hosts. Intravital imaging revealed clusters of largely immotile CX 3 CR1 + monocytes/macrophages in regressing plaques that had been recruited from the periphery. We observed a progressive decrease in CX 3 CR1 + monocytic cells in regressing plaques and a decrease in CCR2 + positron emission tomography signal during 4 months. Cervical transplantation of atherosclerotic mouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques. © 2018 American Heart Association, Inc.

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.

PubMed

Htun, Nay Min; Chen, Yung Chih; Lim, Bock; Schiller, Tara; Maghzal, Ghassan J; Huang, Alex L; Elgass, Kirstin D; Rivera, Jennifer; Schneider, Hans G; Wood, Bayden R; Stocker, Roland; Peter, Karlheinz

2017-07-13

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model.

PubMed

Nahon, Joya E; Hoekstra, Menno; Havik, Stefan R; Van Santbrink, Peter J; Dallinga-Thie, Geesje M; Kuivenhoven, Jan-Albert; Geerling, Janine J; Van Eck, Miranda

2018-05-05

Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined. Finally, susceptibility for atherosclerotic lesion formation was investigated in bone marrow-specific Prg4 knockout (KO) mice. Prg4 mRNA expression was induced 91-fold (p<0.001) in murine initial atherosclerotic lesions and Prg4 protein co-localized with human lesional macrophages. Murine Prg4 KO macrophages showed increased foam cell formation (+2.1-fold, p<0.01). In parallel, the expression of the cholesterol efflux genes ATP-binding cassette transporter A1 and scavenger receptor type B1 was lower (-35%, p<0.05;-40%, p<0.05) in Prg4 KO macrophages. This translated into an impaired cholesterol efflux to high-density lipoprotein (-13%, p<0.001) and apolipoprotein A1 (-8%, p<0.05). Furthermore, Prg4 KO macrophages showed an impaired LPS-induced rise in TNFα secretion as compared to wild-type controls (-31%, p<0.001), indicating a reduced inflammatory response. Combined, these pro- and anti-atherogenic effects did not translate into a significant difference in atherosclerotic lesion formation upon bone marrow-specific deletion of Prg4 in low-density lipoprotein receptor KO mice. Prg4 is present in macrophages in both murine and human atherosclerotic lesions and critically influences macrophage function, but deletion of Prg4 in bone marrow-derived cells does not affect atherosclerotic lesion development. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

PubMed

Kaku, T; Sakurai, S; Furuno, Y; Yashiro, A; Nakashima, Y; Kuroiwa, A

1995-08-01

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left

Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

PubMed

Nelson, J R; Wani, O; May, H T; Budoff, M

2017-04-01

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque.

PubMed

Pan, Xudong; Hou, Rongyao; Ma, Aijun; Wang, Ting; Wu, Mei; Zhu, Xiaoyan; Yang, Shaonan; Xiao, Xing

2017-01-01

Carotid atherosclerosis (AS) is a chronic inflammatory disease of the carotid arterial wall, which is very important in terms of the occurrence of cerebral vascular accidents. Studies have demonstrated that microRNAs (miRNAs) and their target genes are involved in the formation of atherosclerosis and that atorvastatin might reduce atherosclerotic plaques by regulating the expression of miRNAs. However, the related mechanism is not yet known. In this study, we first investigated the effects of atorvastatin on miR-126 and its target gene, i.e., vascular cell adhesion molecule-1 (VCAM-1) in apolipoprotein E-knockout (ApoE-/-) mice with carotid atherosclerotic plaque in vivo. We compared the expressions of miR-126 and VCAM-1 between the control, atherosclerotic model and atorvastatin treatment groups of ApoE-/- mice using RT-PCR and Western blot. We found the miR-126 expression was significantly down-regulated, and the VCAM-1 expression was significantly up-regulated in the atherosclerotic model group, which accelerated the progression of atherosclerosis in the ApoE-/- mice. These results following atorvastatin treatment indicated that miR-126 expression was significantly up-regulated, VCAM-1 expression was significantly down-regulated and atherosclerotic lesions were reduced. The present results might explain the mechanism by which miR-126 is involved in the formation of atherosclerosis in vivo. Our study first indicated that atorvastatin might exert its anti-inflammatory effects in atherosclerosis by regulating the expressions of miR-126 and VCAM-1 in vivo.

Interaction between left ventricular twist mechanics and arterial haemodynamics during localised, non-metabolic hyperaemia with and without blood flow restriction.

PubMed

van Mil, Anke C C M; Pearson, James; Drane, Aimee L; Cockcroft, John R; McDonnell, Barry J; Stöhr, Eric J

2016-04-01

What is the central question of this study? Left ventricular (LV) twist is reduced when afterload is increased, but the meaning of this specific heart muscle response and its impact on cardiac output are not well understood. What is the main finding and its importance? This study shows that LV twist responds even when arterial haemodynamics are altered only locally, and without apparent change in metabolic (i.e. heat-induced) demand. The concurrent decline in cardiac output and LV twist during partial arterial occlusion despite the increased peripheral demand caused by heat stress suggests that LV twist may be involved in the protective sensing of heart muscle stress that can override the provision of the required cardiac output. Whether left ventricular (LV) twist and untwisting rate (LV twist mechanics) respond to localised, peripheral, non-metabolic changes in arterial haemodynamics within an individual's normal afterload range is presently unknown. Furthermore, previous studies indicate that LV twist mechanics may override the provision of cardiac output, but this hypothesis has not been examined purposefully. Therefore, we acutely altered local peripheral arterial haemodynamics in 11 healthy humans (women/men n = 3/8; age 26 ± 5 years) by bilateral arm heating (BAH). Ultrasonography was used to examine arterial haemodynamics, LV twist mechanics and the twist-to-shortening ratio (TSR). To determine the arterial function-dependent contribution of LV twist mechanics to cardiac output, partial blood flow restriction to the arms was applied during BAH (BAHBFR ). Bilateral arm heating increased arm skin temperatures [change (Δ) +6.4 ± 0.9°C, P < 0.0001] but not core temperature (Δ -0.0 ± 0.1°C, P > 0.05), concomitant to increases in brachial artery blood flow (Δ 212 ± 77 ml, P < 0.0001), cardiac output (Δ 495 ± 487 l min(-1) , P < 0.05), LV twist (Δ 3.0 ± 3.5 deg, P < 0.05) and TSR (Δ 3.3 ± 1.3, P < 0.05) but

Atherosclerotic changes of vessels caused by restriction of movement

NASA Technical Reports Server (NTRS)

Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

1980-01-01

The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

EphA2 knockdown attenuates atherosclerotic lesion development in ApoE(-/-) mice.

PubMed

Jiang, Hong; Li, Xinyun; Zhang, Xiaoli; Liu, Yan; Huang, Shanying; Wang, Xiaowei

2014-01-01

The inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined. Eight-week-old male ApoE(-/-) mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis. The lesions formed in the entire aorta and aortic sinus of the ApoE(-/-) mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7%±3.1% versus 25.1%±4.2%; 0.51±0.02mm(2) versus 0.85±0.03mm(2); n=10; P<.05). Furthermore, the lesions in the ApoE(-/-) mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2%±2.9% versus 22.7%±4%; n=10; P<.05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P<.05). Our data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE(-/-) mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

PubMed

Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

2011-07-01

Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Does extubation result in haemodynamic instability in patients following coronary artery bypass grafts?

PubMed

Walthall, H; Ray, S; Robson, D

2001-10-01

Coronary heart disease and its management continue to be at the centre of Government health policy. The present political climate demands clinical effectiveness and best practice should be established, while maintaining the philosophy of cost-effectiveness and resource management. These directives have led practitioners to question the care of patients following coronary artery bypass surgery, in particular the role of mechanical ventilation and the subsequent act of extubation. A retrospective study of 89 patients who had coronary artery bypass grafts (emergency and elective) was undertaken, to establish if extubation had a significant effect on the haemodynamic status of patients with variable degrees of left ventricular function (19% with poor left ventricular function). The study found that extubation was achieved within a mean time of 4.97 hours following return from surgery. Extubation resulted in a significant increase in heart rate (P = 0.001), as well as a respiratory acidosis (pCO2: P = 0.000; pH: P = 0.000). However, the stability of the patient was not compromised, with neither mean arterial blood pressure (P = 0.825) nor oxygenation levels (P = 0.267) being significantly altered by extubation. On multivariate analysis, the act of extubation had no significant effect on any of the dependent variables. These results suggest that it is not extubation alone that has an impact on the haemodynamic stability of patients following coronary artery bypass grafts, but that this is indeed multifactorial. Therefore extubation is 'safe' practice for patients with varying degrees of left ventricular function following coronary artery bypass grafts. Limitations of the study are acknowledged.

Laparoscopic management of retroperitoneal injuries from penetrating abdominal trauma in haemodynamically stable patients.

PubMed

Koto, Modise Zacharia; Matsevych, Oleh Y; Mosai, Fusi; Balabyeki, Moses; Aldous, Colleen

2018-02-27

Laparoscopy is increasingly utilised in the trauma setting. However, its safety and reliability in evaluating and managing retroperitoneal injuries are not known. The aim of this study was to analyse our experience with laparoscopic management of retroperitoneal injuries due to penetrating abdominal trauma (PAT) and to investigate its feasibility, safety and accuracy in haemodynamically stable patients. Over a 4-year period, patients approached laparoscopically with retroperitoneal injuries were analysed. Mechanism, location and severity of injuries were recorded. Surgical procedures, conversion rate and reasons for conversion and outcomes were described. Of the 284 patients with PAT, 56 patients had involvement of retroperitoneum. Stab wounds accounted 62.5% of patients. The mean Injury Severity Score was 7.4 (4-20). Among retroperitoneal injuries, the colon (27%) was the most commonly involved hollow viscera followed by duodenum (5%). The kidney (5%) and the pancreas (4%) were the injured solid organs. The conversion rate was 19.6% and was mainly due to active bleeding (73%). Significantly more patients with gunshot wound were converted to laparotomy (38% vs. 9%). Therapeutic laparoscopy was performed in 36% of patients. There were no recorded missed injuries or mortality. Five (9%) patients developed the Clavien-Dindo Grade 3 complications, three were managed with reoperation, one with drainage/debridement and one with endovascular technique. Laparoscopic management of retroperitoneal injuries is safe and feasible in haemodynamically stable patients with PAT. However, a high conversion rate indicates difficulties in managing these injuries. The requirements are the dexterity in laparoscopy and readiness to convert in the event of bleeding.

Facing emotions in narcolepsy with cataplexy: haemodynamic and behavioural responses during emotional stimulation.

PubMed

de Zambotti, Massimiliano; Pizza, Fabio; Covassin, Naima; Vandi, Stefano; Cellini, Nicola; Stegagno, Luciano; Plazzi, Giuseppe

2014-08-01

Narcolepsy with cataplexy is a complex sleep disorder that affects the modulation of emotions: cataplexy, the key symptom of narcolepsy, is indeed strongly linked with emotions that usually trigger the episodes. Our study aimed to investigate haemodynamic and behavioural responses during emotional stimulation in narco-cataplexy. Twelve adult drug-naive narcoleptic patients (five males; age: 33.3 ± 9.4 years) and 12 healthy controls (five males; age: 30.9 ± 9.5 years) were exposed to emotional stimuli (pleasant, unpleasant and neutral pictures). Heart rate, arterial blood pressure and mean cerebral blood flow velocity of the middle cerebral arteries were continuously recorded using photoplethysmography and Doppler ultrasound. Ratings of valence and arousal and coping strategies were scored by the Self-Assessment Manikin and by questionnaires, respectively. Narcoleptic patients' haemodynamic responses to pictures overlapped with the data obtained from controls: decrease of heart rate and increase of mean cerebral blood flow velocity regardless of pictures' content, increase of systolic blood pressure during the pleasant condition, and relative reduction of heart rate during pleasant and unpleasant conditions. However, when compared with controls, narcoleptic patients reported lower arousal scores during the pleasant and neutral stimulation, and lower valence scores during the pleasant condition, respectively, and also a lower score at the 'focus on and venting of emotions' dimensions of coping. Our results suggested that adult narcoleptic patients, compared with healthy controls, inhibited their emotion-expressive behaviour to emotional stimulation, and that may be related to the development of adaptive cognitive strategies to face emotions avoiding cataplexy. © 2014 European Sleep Research Society.

Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis

PubMed Central

Patel, Chirag Ramanlal; Engineer, Smita R; Shah, Bharat J; Madhu, S

2012-01-01

Background: Dexmedetomidine, an α2 agonist, when used as an adjuvant in general anaesthesia attenuates stress response to various noxious stimuli, maintains perioperative haemodynamic stability and provides sedation without significant respiratory depression postoperatively. Methods: Sixty patients were randomly divided into two groups of 30 each. In group A, fentanyl 2 μg/kg and in group B dexmedetomidine were given intravenously as loading dose of 1 μg/kg over 10 min prior to induction. After induction with thiopentone, in group B, dexmedetomidine was given as infusion at a dose of 0.2–0.8 μg/kg. Sevoflurane was used as inhalation agent in both groups. Haemodynamic variables and entropy (response entropy and state entropy) were recorded continuously. Postoperative sedation and recovery were assessed by sedation score and modified Aldrete's score, respectively. Results: Dexmedetomidine significantly attenuates stress response at intubation with lesser increase in heart rate (10% vs. 17%), systolic blood pressure (6% vs. 23%) and diastolic blood pressure (7% vs. 20%) as compared to the control group (P<0.05). Intraoperatively, an average of 8% fall in systolic blood pressure and 8.16% fall in diastolic pressure in the test group as compared to 3.6% rise in systolic and 3.3% in diastolic pressure of the control group was observed. Postoperatively, the test group showed significant sedation at 2 h as compared to the control group (P=0.00) and recovery was better in the control group for the first 2 h post extubation. Conclusion: Dexmedetomidine attenuates various stress responses during surgery and maintains the haemodynamic stability when used as an adjuvant in general anaesthesia. Also, the sedative action of dexmedetomidine delays recovery for the first few hours post extubation. PMID:23325938

Rank in Self-Defense Forces and risk factors for atherosclerotic disease.

PubMed

Sakuta, Hidenari; Suzuki, Takashi

2005-10-01

Socioeconomic status is associated with prevalence of and risk for atherosclerotic disease. We investigated the relationship between rank in the Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among middle-aged, male, SDFs personnel. Subjects were classified into five groups according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2 (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5 (highest, n = 89). Low rank was associated with current cigarette smoking, alcohol abstaining, and poorer vegetable consumption. It was also associated with prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and high white blood cell counts. Prevalence of obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated with rank in this population. Rank may be regarded as one of the markers that reflect individual health states among middle-aged male personnel.

Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions.

PubMed

Häkkinen, T; Luoma, J S; Hiltunen, M O; Macphee, C H; Milliner, K J; Patel, L; Rice, S Q; Tew, D G; Karkola, K; Ylä-Herttuala, S

1999-12-01

We studied the expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in human atherosclerotic lesions. In addition, approximately 6-fold higher Lp-PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA(2), which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA(2) activity could lead to antiatherogenic effects in the vessel wall.

Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.

PubMed

Scholz, Karl Heinrich; Maier, Sebastian K G; Maier, Lars S; Lengenfelder, Björn; Jacobshagen, Claudius; Jung, Jens; Fleischmann, Claus; Werner, Gerald S; Olbrich, Hans G; Ott, Rainer; Mudra, Harald; Seidl, Karlheinz; Schulze, P Christian; Weiss, Christian; Haimerl, Josef; Friede, Tim; Meyer, Thomas

2018-04-01

The aim of this study was to investigate the effect of contact-to-balloon time on mortality in ST-segment elevation myocardial infarction (STEMI) patients with and without haemodynamic instability. Using data from the prospective, multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients who used emergency medical service transportation and were treated with primary percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within 60 to 180 min from the first medical contact, we found a nearly linear relationship between contact-to-balloon times and mortality in all four STEMI groups. In CS patients with no OHCA, every 10-min treatment delay resulted in 3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related increase in mortality was significantly higher as compared to the two groups of OHCA patients with shock (2.09) and without shock (1.34), as well as to haemodynamically stable patients (0.34, P < 0.0001). In patients with CS, the time elapsing from the first medical contact to primary PCI is a strong predictor of an adverse outcome. This patient group benefitted most from immediate PCI treatment, hence special efforts to shorten contact-to-balloon time should be applied in particular to these high-risk STEMI patients. NCT00794001.

Local extension of HMGB1 in atherosclerotic lesions of human main cerebral and carotid arteries.

PubMed

Umahara, T; Uchihara, T; Koyama, S; Hashimoto, T; Akimoto, J; Haraoka, J; Iwamoto, T

2014-02-01

High mobility group box 1 protein (HMGB1) is a non-histone chromosomal protein which is highly conserved, ubiquitous, and widely distributed. HMGB1 has multiple functions in the nucleus, including the maintenance of nucleosome structure, the regulation of gene transcription, and involvement in DNA recombination. HMBG1 is currently recognized to have a wide range of potential functions and pathological relevance. HMGB1 is released into the extracellular space from necrotic cells and from activated macrophages. HMGB1 binds to the receptor for advanced glycation end products, resulting in the induction of inflammatory cytokines, and to endothelial cell thrombomodulin. HMGB1 neutralization may also reduce the development of atherosclerosis and ameliorate brain infarction. We investigated the immunolocalization of HMGB1 in atherosclerotic lesions of human cerebral and carotid arteries using a specific antibody, and confirmed the detailed expression and cell type localization using double immunofluorolabeling. In the main cerebral arteries, this anti-HMGB1 antibody intensely immunolabeled both normal morphological vascular smooth muscle cells (VSMCs) within the tunica media and infiltrating VSMCs within the intima of thickened fibrous cap plaques. Endothelial cells were also positive for HMGB1. In carotid plaques, HMGB1-like immunoreactivity (IR) was intense in macrophages, although this IR decreased with increasing cell size. Medium-sized foam cells (50-150 μm) were the most intensely stained. This IR was also observed in the nuclei of foam cells and VSMCs. These findings may provide a basis for understanding the association of HMGB1 with atherosclerotic lesions of the cerebral and carotid arteries, and for constructing strategies to counteract atherosclerosis with anti-HMGB1 antibody.

Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

NASA Astrophysics Data System (ADS)

Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

1989-08-01

Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

Engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions.

PubMed

White, K; Büning, H; Kritz, A; Janicki, H; McVey, J; Perabo, L; Murphy, G; Odenthal, M; Work, L M; Hallek, M; Nicklin, S A; Baker, A H

2008-03-01

Targeted delivery of biological agents to atherosclerotic plaques may provide a novel treatment and/or useful tool for imaging of atherosclerosis in vivo. However, there are no known viral vectors that possess the desired tropism. Two plaque-targeting peptides, CAPGPSKSC (CAP) and CNHRYMQMC (CNH) were inserted into the capsid of adeno-associated virus 2 (AAV2) to assess vector retargeting. AAV2-CNH produced significantly higher levels of transduction than unmodified AAV2 in human, murine and rat endothelial cells, whereas transduction of nontarget HeLa cells was unaltered. Transduction studies and surface plasmon resonance suggest that AAV2-CNH uses membrane type 1 matrix metalloproteinase as a surface receptor. AAV2-CAP only produced higher levels of transduction in rat endothelial cells, possibly because the virus was found to be affected by proteasomal degradation. In vivo substantially higher levels of both peptide-modified AAV2 vectors was detected in the brachiocephalic artery (site of advanced atherosclerotic plaques) and aorta, whereas reduced levels were detected in all other organs examined. These results suggest that in the AAV2 platform the peptides are exposed on the capsid surface in a way that enables efficient receptor binding and so creates effective atherosclerotic plaque targeted vectors.

Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

PubMed

Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

2016-04-01

Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

Lung recruitment manoeuvres do not cause haemodynamic instability or oxidative stress but improve oxygenation and lung mechanics in a newborn animal model: an observational study.

PubMed

de la Osa, Agustín Mendiola; Garcia-Fernandez, Javier; Llorente-Cantarero, Francisco J; Gil-Campos, Mercedes; Muñoz-Villanueva, María C; De la Torre Aguilar, María J; de la Rosa, Ignacio Ibarra; Pérez-Navero, Juan L

2014-09-01

Lung recruitment manoeuvres in neonates during anaesthesia are not performed routinely due to concerns about causing barotrauma, haemodynamic instability and oxidative stress. To assess the influence of recruitment manoeuvres and positive end-expiratory pressure (PEEP) on haemodynamics, oxidative stress, oxygenation and lung mechanics. A prospective experimental study. Experimental Unit, La Paz University Hospital, Madrid, Spain. Eight newborn piglets (<48 h) with healthy lungs under general anaesthesia. The recruitment manoeuvres in pressure-controlled ventilation (PCV) were performed along with a constant driving pressure of 15 cmH2O. After the recruitment manoeuvres, PEEP was reduced in a stepwise fashion to find the maximal dynamic compliance step (maxCDyn-PEEP). Blood oxidative stress biomarkers (lipid peroxidation products, protein carbonyls, total glutathione, oxidised glutathione, reduced glutathione and activity of glutathione peroxidase) were analysed. Haemodynamic parameters, arterial partial pressure of oxygen (paO2), tidal volume (Vt), dynamic compliance (Cdyn) and oxidative stress biomarkers were measured. The recruitment manoeuvres did not induce barotrauma. Haemodynamic instability was not detected either in the maximum pressure step (overdistension step 5) or during the entire process. No substantial differences were observed in blood oxidative stress parameters analysed as compared with their baseline values (with 0 PEEP) or the values obtained 180 min after the onset of the recruitment manoeuvres (optimal PEEP). Significant maximal values were achieved in step 14 with an increase in paO2 (32.43 ± 8.48 vs. 40.39 ± 15.66 kPa; P = 0.037), Vt (47.75 ± 13.59 vs. 73.87 ± 13.56 ml; P = 0.006) and Cdyn (2.50 ± 0.64 vs. 4.75 ± 0.88 ml cmH2O; P < 0.001). Maximal dynamic compliance step (maxCdyn-PEEP) was 2 cmH2O. Recruitment manoeuvres in PCV with a constant driving pressure are a well tolerated open

pyNS: an open-source framework for 0D haemodynamic modelling.

PubMed

Manini, Simone; Antiga, Luca; Botti, Lorenzo; Remuzzi, Andrea

2015-06-01

A number of computational approaches have been proposed for the simulation of haemodynamics and vascular wall dynamics in complex vascular networks. Among them, 0D pulse wave propagation methods allow to efficiently model flow and pressure distributions and wall displacements throughout vascular networks at low computational costs. Although several techniques are documented in literature, the availability of open-source computational tools is still limited. We here present python Network Solver, a modular solver framework for 0D problems released under a BSD license as part of the archToolkit ( http://archtk.github.com ). As an application, we describe patient-specific models of the systemic circulation and detailed upper extremity for use in the prediction of maturation after surgical creation of vascular access for haemodialysis.

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti

Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.

PubMed Central

Johnson-Tidey, R. R.; McGregor, J. L.; Taylor, P. R.; Poston, R. N.

1994-01-01

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7513951

Acute effects of 3G mobile phone radiations on frontal haemodynamics during a cognitive task in teenagers and possible protective value of Om chanting.

PubMed

Bhargav, Hemant; N K, Manjunath; Varambally, Shivarama; Mooventhan, A; Bista, Suman; Singh, Deepeshwar; Chhabra, Harleen; Venkatasubramanian, Ganesan; T M, Srinivasan; H R, Nagendra

2016-06-01

Mobile phone induced electromagnetic field (MPEMF) as well as chanting of Vedic mantra 'OM' has been shown to affect cognition and brain haemodynamics, but findings are still inconclusive. Twenty right-handed healthy teenagers (eight males and 12 females) in the age range of 18.25 ± 0.44 years were randomly divided into four groups: (1) MPONOM (mobile phone 'ON' followed by 'OM' chanting); (2) MPOFOM (mobile phone 'OFF' followed by 'OM' chanting); (3) MPONSS (mobile phone 'ON' followed by 'SS' chanting); and (4) MPOFSS (mobile phone 'OFF' followed by 'SS' chanting). Brain haemodynamics during Stroop task were recorded using a 64-channel fNIRS device at three points of time: (1) baseline, (2) after 30 min of MPON/OF exposure, and (3) after 5 min of OM/SS chanting. RM-ANOVA was applied to perform within- and between-group comparisons, respectively. Between-group analysis revealed that total scores on incongruent Stroop task were significantly better after OM as compared to SS chanting (MPOFOM vs MPOFSS), pre-frontal activation was significantly lesser after OM as compared to SS chanting in channel 13. There was no significant difference between MPON and MPOF conditions for Stroop performance, as well as brain haemodynamics. These findings need confirmation through a larger trial in future.

Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

PubMed Central

Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

1998-01-01

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

High purity tocotrienols attenuate atherosclerotic lesion formation in apoE-KO mice.

PubMed

Shibata, Akira; Kobayashi, Teiko; Asai, Akira; Eitsuka, Takahiro; Oikawa, Shinichi; Miyazawa, Teruo; Nakagawa, Kiyotaka

2017-10-01

Previous studies have demonstrated that tocotrienol (T3) has antiatherogenic effects. However, the T3 preparations used in those studies contained considerable amounts of tocopherol (Toc), which might affect the biological activity of T3. There is little information on the effect of highly purified T3 on atherosclerosis formation. This study investigated the effect of high-purity T3 on atherosclerotic lesion formation and the underlying mechanisms. Male apolipoprotein E knockout (apoE-KO) mice were fed a cholesterol-containing diet either alone or supplemented with T3 concentrate (Toc-free T3) or with α-Toc for 12 weeks. ApoE-KO mice fed the 0.2% T3-supplemented diet showed reduced atherosclerotic lesion formation in the aortic root. The 0.2% T3 diet induced Slc27a1 and Ldlr gene expression levels in the liver, whereas the α-Toc-supplemented diet did not affect those expression levels. T3 was predominantly deposited in fat tissue in the T3 diet-fed mice, whereas α-Toc was preferentially accumulated in liver in the α-Toc diet-fed mice. Considered together, these data demonstrate that dietary T3 exerts anti-atherosclerotic effect in apoE-KO mice. The characteristic tissue distribution and biological effects of T3, that are substantially different from those of Toc, may contribute to the antiatherogenic properties of T3. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis.

PubMed

Ringle, Anne; Levy, Franck; Ennezat, Pierre-Vladimir; Le Goffic, Caroline; Castel, Anne-Laure; Delelis, François; Menet, Aymeric; Malaquin, Dorothée; Graux, Pierre; Vincentelli, André; Tribouilloy, Christophe; Maréchaux, Sylvestre

We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm 2 or<1cm 2 ) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic

Chest shielding for prevention of a haemodynamically significant patent ductus arteriosus in preterm infants receiving phototherapy.

PubMed

Bhola, Kavita; Foster, Jann P; Osborn, David A

2015-11-03

Patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Phototherapy is a common treatment for jaundice in preterm infants. However, phototherapy has been associated with failure of closure of the ductus arteriosus in preterm infants. To determine if chest shielding of preterm infants receiving phototherapy reduces the incidence of clinically and/or haemodynamically significant PDA and reduces morbidity secondary to PDA. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2015, Issue 3), MEDLINE, EMBASE, CINAHL, previous reviews, cross-references, abstracts, proceedings of scientific meetings, and trial registries through March 2015. Randomised controlled trials (RCTs), cluster-RCTs, or quasi-RCTs of chest shielding during phototherapy compared to sham shielding or no shielding for the prevention of a haemodynamically or clinically significant PDA in preterm infants. Three review authors independently assessed studies for eligibility and quality and extracted data. We defined a clinically significant PDA as the presence of a PDA with clinical signs of an effect on organ function attributable to the ductus arteriosus. We defined a haemodynamically significant PDA as clinical and/or echocardiographic signs of a significant ductus arteriosus effect on blood flow. We included two small trials enrolling very preterm infants (Rosenfeld 1986; Travadi 2006). We assessed both as at high risk of bias. No study reported clinically significant PDA, defined as the presence of a PDA with clinical symptoms or signs attributable to the effect of a ductus arteriosus on organ function. Rosenfeld 1986 reported a non-significant reduction in haemodynamically significant PDA with left atrial to aortic root ratio greater than 1.2 (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.05 to 1.01; 74 infants) but a statistically significant risk difference (RD -0.18, 95% CI -0.34 to -0.03; number needed to

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

USDA-ARS?s Scientific Manuscript database

Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers.

PubMed

Elsayed, Mahmoud; Bulur, Serkan; Kalla, Aditi; Ahmed, Mustafa I; Hsiung, Ming C; Uygur, Begum; Alagic, Nermina; Sungur, Aylin; Singh, Satinder; Nanda, Navin C

2016-08-01

We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two-dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other. © 2016, Wiley Periodicals, Inc.

Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2 inhibition on resting haemodynamics and responses to exendin-4

PubMed Central

Gardiner, S M; March, J E; Kemp, P A; Bennett, T

2006-01-01

Background and purpose: Interactions between the NO system and the cyclooxygenase systems may be important in cardiovascular regulation. Here we measured the effects of acute cyclooxygenase-2 inhibition (with parecoxib), alone and in combination with NOS inhibition (with N G-nitro-L-arginine methyl ester (L-NAME)), on resting cardiovascular variables and on responses to the glucagon-like peptide 1 agonist, exendin-4, which causes regionally-selective vasoconstriction and vasodilatation. Experimental approach: Rats were instrumented with flow probes and intravascular catheters to measure regional haemodynamics in the conscious, freely moving state. L-NAME was administered as a primed infusion 180 min after administration of parecoxib or vehicle, and exendin-4 was given 60 min after the onset of L-NAME infusion. Key results: Parecoxib had no effect on resting cardiovascular variables or on responses to L-NAME. Exendin-4 caused a pressor response accompanied by tachycardia, mesenteric vasoconstriction and hindquarters vasodilatation. Parecoxib did not affect haemodynamic responses to exendin-4, but L-NAME inhibited its hindquarters vasodilator and tachycardic effects. When combined, L-NAME and parecoxib almost abolished the hindquarters vasodilatation while enhancing the pressor response. Conclusions and implications: Cyclooxygenase-2-derived products do not affect basal haemodynamic status in conscious normotensive rats, or influence the NO system acutely. The inhibitory effects of L-NAME on the hindquarters vasodilator and tachycardic effects of exendin-4 are consistent with a previous study that showed those events to be β-adrenoceptor mediated. The additional effect of parecoxib on responses to exendin-4 in the presence of L-NAME, is consistent with other evidence for enhanced involvement of vasodilator prostanoids when NO production is reduced. PMID:17016494

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

PubMed

Jo, Javier A; Fang, Qiyin; Papaioannou, Thanassis; Baker, J Dennis; Dorafshar, Amir H; Reil, Todd; Qiao, Jian-Hua; Fishbein, Michael C; Freischlag, Julie A; Marcu, Laura

2006-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

Jo, Javier A.; Fang, Qiyin; Papaioannou, Thanassis; Baker, J. Dennis; Dorafshar, Amir; Reil, Todd; Qiao, Jianhua; Fishbein, Michael C.; Freischlag, Julie A.; Marcu, Laura

2006-03-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

PubMed Central

Jo, Javier A.; Fang, Qiyin; Papaioannou, Thanassis; Baker, J. Dennis; Dorafshar, Amir H.; Reil, Todd; Qiao, Jian-Hua; Fishbein, Michael C.; Freischlag, Julie A.; Marcu, Laura

2007-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability. PMID:16674179

αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.

PubMed

Vancraeynest, David; Roelants, Véronique; Bouzin, Caroline; Hanin, François-Xavier; Walrand, Stephan; Bol, Vanesa; Bol, Anne; Pouleur, Anne-Catherine; Pasquet, Agnès; Gerber, Bernhard; Lesnik, Philippe; Huby, Thierry; Jamar, François; Vanoverschelde, Jean-Louis

2016-12-01

αVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated (99m)Tc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice. Apolipoprotein E-negative (ApoE(-/-)) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with (99m)Tc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE(-/-) mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology. Tracer uptake was significantly higher in ApoE(-/-) mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 (99m)Tc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73). (99m)Tc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for

Toll-like receptor 7 stimulation by imiquimod induces macrophage autophagy and inflammation in atherosclerotic plaques.

PubMed

De Meyer, Inge; Martinet, Wim; Schrijvers, Dorien M; Timmermans, Jean-Pierre; Bult, Hidde; De Meyer, Guido R Y

2012-05-01

Atherosclerotic plaques tend to rupture as a consequence of a weakened fibrous cap, particularly in the shoulder regions where most macrophages reside. Macrophages express Toll-like receptors to recognize pathogens and eliminate intracellular pathogens by inducing autophagy. Because Toll-like receptor 7 (TLR7) is thought to be expressed in macrophages but not in smooth muscle cells (SMCs), we investigated whether induction of macrophage autophagic death by TLR7 ligand imiquimod can affect the composition of atherosclerotic plaques in favor of their stability. Immunohistochemical staining of human carotid plaques as well as Western blotting of cultured macrophages and SMCs confirmed that TLR7 was expressed in macrophages, but not in SMCs. In vitro experiments showed that only TLR7 expressing cells underwent imiquimod-induced cell death, which was characterized by autophagosome formation. Imiquimod-treated macrophages activated nuclear factor-κB (NF-κB) and released pro-inflammatory cytokines and chemokines. This effect was inhibited by the glucocorticoid dexamethasone. Imiquimod-induced cytokine release was significantly decreased in autophagy-deficient macrophages because these cells died by necrosis at an accelerated pace. Local in vivo administration of imiquimod to established atherosclerotic lesions in rabbit carotid arteries induced macrophage autophagy without induction of cell death, and triggered cytokine production, upregulation of vascular adhesion molecule-1, infiltration of T-lymphocytes, accumulation of macrophages and enlargement of plaque area. Treatment with dexamethasone suppressed these pro-inflammatory effects in vivo. SMCs and endothelial cells in imiquimod-treated plaques were not affected. In conclusion, imiquimod induces macrophage autophagy in atherosclerotic plaques, but stimulates plaque progression through cytokine release and enhanced infiltration of inflammatory cells.

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

PubMed

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

PubMed

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

A fluorescence lifetime spectroscopy study of matrix metalloproteinases -2 and -9 in human atherosclerotic plaque

PubMed Central

Phipps, Jennifer E.; Hatami, Nisa; Galis, Zorina S.; Baker, J. Dennis; Fishbein, Michael C.; Marcu, Laura

2011-01-01

Matrix metalloproteinase (MMP) -2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system. PMID:21770037

Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

PubMed

Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

2015-08-01

Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Sanjay, E-mail: sanjay@louisville.ed; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, KY 40202; Vladykovskaya, Elena N.

2009-11-15

Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO{sub 2} in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO{sub 2} in drinking water) increased the lesion formation andmore » macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.« less

Comparison of the Effects of Thiopental Sodium and Propofol on Haemodynamics, Awareness and Newborns During Caesarean Section Under General Anaesthesia.

PubMed

Çakırtekin, Vedat; Yıldırım, Ahmet; Bakan, Nurten; Çelebi, Nevin; Bozkurt, Özkan

2015-04-01

To compare the effects of propofol and thiopental on haemodynamics, awareness and newborns in pregnant women undergoing elective caesarean section. Seventy pregnant women were assigned into two equal groups. For anaesthesia induction, 2 mg kg(-1) propofol (Group P) and 5 mg kg(-1) thiopental (Group T) were administered. Maternal haemodynamic parameters and bispectral index (BIS) values were recorded before induction, in 1-minute intervals within the first 10 minutes after induction and in 5-minute intervals thereafter, during skin incision, uterine incision, removal of infant, uterine sutures, skin sutures, eye opening and extubation in all cases. Cord blood gas analysis and 1- and 5-minute APGAR scores were recorded. In all cases, a keyword was spelled to ear during removal of the infant, and at the first postoperative hour, patients were questioned. Important time periods of surgery and anaesthesia and also the first postoperative hour haemodynamic values, pain scores, nausea and vomiting were noted. The demographic data were similar among cases. In Group T, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) at the first 2 minutes after induction and heart rate (HR) at almost all time points were significantly higher. BIS values from induction to the eighth minute and skin incision, uterine incision and removal of the infant were lower in Group P. No patient remembered the keyword spelled, while 4 patients reported dreaming during general anaesthesia. The effects of propofol and thiopental sodium on 1- and 5-minute APGAR scores, cord blood gas values and postoperative visual analogue scale (VAS) scores were similar. Propofol is a more appropriate anaesthetic agent than thiopental in anaesthesia for caesareans, since it provides better anaesthestic depth and more rapid recovery.

Transcatheter aortic valve implantation of a second-generation valve for pure aortic regurgitation: procedural outcome, haemodynamic data and follow-up.

PubMed

Schlingloff, Friederike; Schäfer, Ulrich; Frerker, Christian; Schmoeckel, Michael; Bader, Ralf

2014-09-01

The second-generation Jenavalve prosthesis (Jenavalve Technology, Inc., Munich, Germany) is the first transcatheter valve Conformité Européene (CE) marked for treatment of both aortic stenosis (AS) and pure aortic regurgitation (AR). Although the feasibility of the Jenavalve transcatheter aortic valve implantation (TAVI) in patients with pure AR has been described, haemodynamic and follow-up data are lacking. We report on a series of 10 transapical Jenavalve implantations for pure AR between December 2012 and September 2013. The patients were determined for TAVI by heart team decision at high surgical risk [log EuroSCORE (European System for Cardiac Operative Risk Evaluation) >20%], frailty or Charlson Comorbidity Index (CCI). Transaortic gradients and right heart haemodynamics were measured invasively before and after TAVI. Ventriculography and transoesophageal echocardiography were used to determine paravalvular regurgitation. All-cause mortality, NYHA functional class and echocardiographic measurements were followed up at 30 days and at 3, 9 and 12 months postoperatively. Overall, mean age was 79 ± 9 years, mean left ventricular ejection fraction 50 ± 17% and mean log EuroSCORE 28.3 ± 17.1%. There were no perioperative complications. Paravalvular regurgitation immediately after implantation was graded none (n = 6), trace (n = 3) or mild (n = 1). Overall 30-day mortality was 30% (3/10). Three patients refused further treatment, such as haemodialysis or treatment of mitral regurgitation. Rate for pacemaker implantation was 2/10 (20%). Intraprocedural success and haemodynamic data in our cases were good. The mortality in our group highlighted the importance of careful patient selection, especially for this pathology. The Jenavalve prosthesis proved to be suitable for treatment of AR in surgical high-risk patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

SRXRF Study of Chemical Elements Content in the Atherosclerotic Plaque of Heart Vessels

NASA Astrophysics Data System (ADS)

Zhuravskaya, E. Ya.; Savchenko, T. I.; Chankina, O. V.; Polonskaya, Ya. V.; Chernyavskii, A. M.; Ragino, Yu. I.; Shcherbakova, L. V.

The SRXRF method has made it possible, for the first time, to determine the multielement composition in the atherosclerotic substrates of heart vessels after surgical interventions. The main advantage of the method is the possibility to analyze small samples without their destruction. As the amount of material to test is insufficient, we have developed a special technique for sample preparation. The concentrations of K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Sr, Zr, and Pb were measured in stable and unstable plaques. In all the samples studied, Ca is dominating, particularly, in the unstable plaque. No reliable difference was established for other elements measured. A high degree of the association of Ca with Fe, Zn and Sr has been revealed in the atherosclerotic plaques. Measurements were performed using SR from the VEPP-3 storage ring.

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

PubMed Central

Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

2013-01-01

Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

Morphologic characteristics of central pulmonary thromboemboli predict haemodynamic response in massive pulmonary embolism.

PubMed

Podbregar, Matej; Voga, Gorazd; Krivec, Bojan

2004-08-01

On hospital admission, the morphology of the central pulmonary artery thromboemboli is an independent predictor of 30-day mortality in patients with massive pulmonary embolism (MPE). This may be due to the differential susceptibility of thromboemboli to thrombolysis. The aim of this study was to assess haemodynamic response to treatment in patients with MPE and morphologically different thromboemboli. Prospective observational study. An 11-bed closed medical ICU at a 860-bed community general hospital. Twelve consecutive patients with shock or hypotension due to MPE and central pulmonary thromboemboli detected by transesophageal echocardiography who were treated with thrombolysis between January 2000 through April 2002. Patients were divided into two groups according to the characteristics of detected central pulmonary thromboemboli: group 1, thrombi with one or more long, mobile parts; and group 2, immobile thrombi. Urokinase infusion was terminated when mixed venous oxygen saturation was stabilized above 60% for 15 min. At 2 h, the total pulmonary vascular resistance index was reduced more in group 1 than group 2 [from 27+/-12 mmHg/(l.min.m(2)) to 14+/-6 mmHg/(l.min.m(2)) (-52%) vs 27+/-8 mmHg/(l.min.m(2)) to 23+/-10 mmHg/(l.min.m(2)) (-15%), respectively, P=0.04]. In group 1 thrombolysis was terminated earlier than group 2 (89+/-40 min vs 210+/-62 min, respectively, P= 0.0024). The cumulative dose of urokinase used in group 1 was lower than group 2 (1.7+/-0.3 M i.u. vs 2.7+/-0.5 M i.u., respectively, P= 0.023). Haemodynamic stabilization is achieved faster in patients with mobile central thromboemboli detected by transesophageal echocardiography during MPE.

Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)

ClinicalTrials.gov

2018-01-24

Hypertension; Hypertension Resistant to Conventional Therapy; Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent

Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease.

PubMed

Gregg, L Parker; Tio, Maria Clarissa; Li, Xilong; Adams-Huet, Beverley; de Lemos, James A; Hedayati, S Susan

2018-06-06

Monocyte chemoattractant protein-1 -(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = -0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4-2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0-2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1-2.3]) after adjusting for CV risk factors. Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD. © 2018 S. Karger AG, Basel.

Renal function during pregnancy may predict risk of future hospitalization due to atherosclerotic-related morbidity.

PubMed

Wolak, Talya; Shoham-Vardi, Ilana; Sergienko, Ruslan; Sheiner, Eyal

2016-02-01

This study aims to examine whether renal function during pregnancy can serve as a surrogate marker for the risk of developing atherosclerotic-related morbidity. A case-control study, including women who gave birth at a tertiary referral medical centre during 2000-2012. This population was divided into cases of women who were subsequently hospitalized for atherosclerotic morbidity during the study period and age-matched controls. From the study population, we retrieved two groups: the creatinine (Cr) group: women who had at least one Cr measurement (4945 women) and the urea group: women who had at least one urea measurement (4932 women) during their pregnancies. In the Cr and urea group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The mean follow-up period in the Cr and urea group was 61.7 ± 37.0 and 57.3 ± 36.0 months, respectively. Cox proportional hazards models (controlling for confounders: gestational hypertension, gestational diabetes, obesity, maternal age, creatinine level (for urea), and gestational week) were used to estimate the adjusted hazard ratios (HR) for hospitalizations. A significant association was documented between renal function during pregnancy and long-term atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy index of ≥89 μmol/L was associated with a significant increased risk for hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37-6.19 P = 0.005) and urea level ≤7 mmol/L was independently associated with reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P = 0.001). Renal function abnormality during pregnancy may reveal occult predisposition to atherosclerotic morbidity years after childbirth. © 2015 Asian Pacific Society of Nephrology.

Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

PubMed Central

Pedersen, Sune F; Hag, Anne Mette F; Klausen, Thomas L; Ripa, Rasmus S; Bodholdt, Rasmus P; Kjær, Andreas

2014-01-01

Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD). It is the leading cause of morbidity and mortality in the Western world today and is set to become the prevailing disease and major cause of death worldwide by 2020. In the 1950s surgical intervention was introduced to treat symptomatic patients with high-grade carotid artery stenosis due to atherosclerosis – a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke. However, it is known that patients with low to intermediate artery stenosis may still experience ischemic events, leading clinicians to consider plaque composition as an important feature of atherosclerosis. Today molecular imaging can be used for characterization, visualization and quantification of cellular and subcellular physiological processes as they take place in vivo; using this technology we can obtain valuable information on atherosclerostic plaque composition. Applying molecular imaging clinically to atherosclerotic disease therefore has the potential to identify atherosclerotic plaques vulnerable to rupture. This could prove to be an important tool for the selection of patients for CEA surgery in a health system increasingly focused on individualized treatment. This review focuses on current advances and future developments of in vivo atherosclerosis PET imaging in man. PMID:24289282

Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images

PubMed Central

Ughi, Giovanni Jacopo; Adriaenssens, Tom; Sinnaeve, Peter; Desmet, Walter; D’hooge, Jan

2013-01-01

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution <20µm, image analysis in terms of tissue composition is currently performed by a time-consuming manual procedure based on the qualitative interpretation of image features. We illustrate an algorithm for the automated and systematic characterization of IVOCT atherosclerotic tissue. The proposed method consists in a supervised classification of image pixels according to textural features combined with the estimated value of the optical attenuation coefficient. IVOCT images of 64 plaques, from 49 in vivo IVOCT data sets, constituted the algorithm’s training and testing data sets. Validation was obtained by comparing automated analysis results to the manual assessment of atherosclerotic plaques. An overall pixel-wise accuracy of 81.5% with a classification feasibility of 76.5% and per-class accuracy of 89.5%, 72.1% and 79.5% for fibrotic, calcified and lipid-rich tissue respectively, was found. Moreover, measured optical properties were in agreement with previous results reported in literature. As such, an algorithm for automated tissue characterization was developed and validated using in vivo human data, suggesting that it can be applied to clinical IVOCT data. This might be an important step towards the integration of IVOCT in cardiovascular research and routine clinical practice. PMID:23847728

Anti-atherosclerotic effects of pravastatin in brachiocephalic artery in comparison with en face aorta and aortic roots in ApoE/LDLR-/- mice.

PubMed

Kostogrys, Renata B; Franczyk-Zarow, Magdalena; Gasior-Glogowska, Marlena; Kus, Edyta; Jasztal, Agnieszka; Wrobel, Tomasz P; Baranska, Malgorzata; Czyzynska-Cichon, Izabela; Drahun, Anna; Manterys, Angelika; Chlopicki, Stefan

2017-02-01

Cholesterol-dependent and independent mechanisms were proposed to explain anti-atherosclerotic action of statins in humans. However, their effects in murine models of atherosclerosis have not been consistently demonstrated. Here, we studied the effects of pravastatin on atherosclerosis in ApoE/LDLR -/- mice fed a control and atherogenic diet. ApoE/LDLR -/- mice were fed a control (CHOW) or an atherogenic (Low Carbohydrate High Protein, LCHP) diet. Two doses of pravastatin (40mg/kg and 100mg/kg) were used. The anti-atherosclerotic effects of pravastatin in en face aorta, cross-sections of aortic roots and brachiocephalic artery (BCA) were analysed. The lipid profile was determined. Fourier Transform Infrared Spectroscopy followed by Fuzzy C-Means (FCM) clustering was used for the quantitative assessment of plaque composition. Treatment with pravastatin (100mg/kg) decreased total and LDL cholesterol only in the LCHP group, but displayed a pronounced anti-atherosclerotic effect in BCA and abdominal aorta. The anti-atherosclerotic effect of pravastatin (100mg/kg) in BCA was associated with significant alterations of the chemical plaque composition, including a fall in cholesterol and cholesterol esters contents independently on total cholesterol and LDL concentration in plasma. Pravastatin at high (100mg/kg), but not low dose displayed a pronounced anti-atherosclerotic effect in ApoE/LDLR -/- mice fed a CHOW or LCHP diet that was remarkable in BCA, visible in en face aorta, whereas it was not observed in aortic roots, suggesting that previous inconsistencies might have been due to the various sites of atherosclerotic plaque analysis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

A fluorescence lifetime spectroscopy study of matrix metalloproteinases-2 and -9 in human atherosclerotic plaque.

PubMed

Phipps, Jennifer E; Hatami, Nisa; Galis, Zorina S; Baker, J Dennis; Fishbein, Michael C; Marcu, Laura

2011-09-01

Matrix metalloproteinase (MMP)-2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice

PubMed Central

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-01-01

Background and Purpose Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Experimental Approach Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Key Results Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (−70%) and secretion (−28%) by peritoneal macrophages. Conclusions and Implications Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. PMID:25572138

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

PubMed

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties

PubMed Central

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang

2015-01-01

Background and objectives Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Subjects and methods Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Results Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with

[The relationship between ophthalmic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance].

PubMed

Liu, L; Yuan, S; Yang, W

1999-04-01

To explore the relationship between the optic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance. The color Doppler imaging was used to study blood velocity in the ophthalmic, the central retinal and the short posterior ciliary arteries in 34 patients with primary open angle glaucoma, 31 patients with low tension glaucoma and 90 healthy controls. The peak systolic velocity(PSV), the end diastolic velocity (EDV) and resistive index (RI) in each artery were measured, moreover the nailfold microcirculation and blood viscosity in each patient were examined. Compared with the control group, the PSV and EDV of the central retinal arteries were significantly lower while the RI of the central retinal arteries was significantly higher in both POAG and LTG patients. The RI of the short posterior ciliary arteries however was significantly higher in POAG. Nailfold microcirculation shows that some important parameters, including flow pattern, loop surrounding, morphological weighted value, total weighted value and capillary deformity rate in the two glaucoma groups were higher, whereas the flow velocity was lower than in the control group. The plasm viscosity and the whole blood viscosity (low spear) were higher than normal. According to our measurements, the nailfold microcirculation and blood viscosity was worse at the end stage of glaucoma than at early stage. The correlative analysis between measurement results of color doppler imaging and microcirculation and heamorrheology showed that nailfold microcirculation morphological weighted value was negatively correlated with the EDV of the central retinal artery and positively correlated with the RI of the central retinal artery in LTG patients. The abnormity of ocular haemodynamics and systemic microcirculation and blood viscosity is one important factor of optic nerve damage in glaucoma.

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity†

PubMed Central

Olson, Emilia S.; Whitney, Michael A.; Friedman, Beth; Aguilera, Todd A.; Crisp, Jessica L.; Baik, Fred M.; Jiang, Tao; Baird, Stephen M.; Tsimikas, Sotirios; Tsien, Roger Y.

2012-01-01

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL–ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL–ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL–ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL–ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques. PMID:22534729

In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity.

PubMed

Olson, Emilia S; Whitney, Michael A; Friedman, Beth; Aguilera, Todd A; Crisp, Jessica L; Baik, Fred M; Jiang, Tao; Baird, Stephen M; Tsimikas, Sotirios; Tsien, Roger Y; Nguyen, Quyen T

2012-06-01

Thrombin and other coagulation enzymes have been shown to be important during atherosclerotic disease development. Study of these proteases is currently limited because of lack of robust molecular imaging agents for imaging protease activity in vivo. Activatable cell penetrating peptides (ACPPs) have been used to monitor MMP activity in tumors and, in principle, can be modified to detect other proteases. We have developed a probe that incorporates the peptide sequence DPRSFL from the proteinase activated receptor 1 (PAR-1) into an ACPP and shown that it is preferentially cleaved by purified thrombin. Active thrombin in serum cleaves DPRSFL-ACPP with >90% inhibition by lepirudin or argatroban. The DPRSFL-ACPP cleavage product accumulated in advanced atherosclerotic lesions in living mice, with 85% reduction in retention upon pre-injection of mice with hirudin. Uptake of the ACPP cleavage product was highest in plaques with histological features associated with more severe disease. Freshly resected human atheromas bathed in DPRSFL-ACPP retained 63% greater cleavage product compared to control ACPP. In conclusion, DPRSFL-ACPP can be used to study thrombin activity in coagulation and atherosclerosis with good spatial and temporal resolution. Thrombin-sensitive ACPPs may be developed into probes for early detection and intraoperative imaging of high risk atherosclerotic plaques.

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

PubMed

Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

PubMed

Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

2013-01-01

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice

NASA Astrophysics Data System (ADS)

Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric

2017-02-01

Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

Haemodynamic stability during general anaesthesia for intra-ocular surgery: the effect of topical oxybuprocaine.

PubMed

Lytle, J; Thomas, N F

1992-07-01

Local anaesthesia is frequently used in combination with light general anaesthesia to reduce the reflex responses to surgical stimulation. This combination has not previously been evaluated for intra-ocular surgery. During cataract extraction under general anaesthesia, the effect of topical anaesthesia with oxybuprocaine 0.4% on the pressor response was compared with normal saline in a control group. The simple technique of instilling local anaesthetic drops into the conjunctival sac blocked the pain pathway sufficiently to prevent the pressor response to surgical stimulation (p less than 0.001). Higher inspired concentrations of enflurane were required in the control group to achieve and maintain haemodynamic stability (p less than 0.001).

Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice

PubMed Central

Pont, Isabel; Calatayud-Pascual, Aracely; López-Castellano, Alicia; Albelda, Elena P.; García-España, Enrique; Martí-Bonmatí, Luis; Frias, Juan C.

2018-01-01

Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment. PMID:29338009

Percutaneous transcatheter arterial embolization in haemodynamically stable patients with blunt splenic injury

PubMed Central

Popovic, Peter; Stanisavljevic, Dragoje; Jeromel, Miran

2010-01-01

Background The nonoperative management of the blunt splenic injury in haemodynamically stable patients has become an accepted treatment in recent years. We present a case of the blunt splenic injury successfully treated by supraselective embolization with microspheres. Case report. A young hockey player was brought to the Emergency Department with the history of blunt abdominal trauma 2 h earlier. A Grade III splenic injury with haemoperitoneum was diagnosed on sonographic evaluation and the patient was treated with the selective distal splenic artery embolization with microspheres. Postprocedural ultrasound and computed tomography follow-up a year later revealed only a small area of parenchymal irregularity. Conclusions The percutaneous splenic arterial embolization has a major role in the management of traumatic splenic injuries. Embolization is particularly beneficial in injuries of grade III or higher. PMID:22933888

CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas

PubMed Central

Butcher, Matthew J.; Wu, Chih-I; Waseem, Tayab

2016-01-01

The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A+ cells play a role in this disease. Although elevated number of CD4+ IL-17A+ (Th17) and IL-17A+TCRγδ+ T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A+ T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6 GFP/GFP) apolipoprotein E-deficient (Apoe −/−) mice to investigate the involvement of CXCR6 in the recruitment IL-17A+ T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A+TCRγδ+ T cells within aged Cxcr6 GFP/GFP Apoe −/− aortas, in comparison with age-matched Cxcr6 GFP/+ Apoe −/− aortas. Although CXCR6-sufficient IL-17A+ T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A+ T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6 GFP/GFP Apoe −/− IL-17A+ T cells into the aortas of Apoe −/− recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A+TCRγδ+ T-cell recruitment into atherosclerotic lesions. PMID:26614640

CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas.

PubMed

Butcher, Matthew J; Wu, Chih-I; Waseem, Tayab; Galkina, Elena V

2016-05-01

The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A(+) T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6 (GFP/GFP) ) apolipoprotein E-deficient (Apoe (-/-) ) mice to investigate the involvement of CXCR6 in the recruitment IL-17A(+) T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A(+)TCRγδ(+) T cells within aged Cxcr6 (GFP/GFP) Apoe (-/-) aortas, in comparison with age-matched Cxcr6 (GFP/+) Apoe (-/-) aortas. Although CXCR6-sufficient IL-17A(+) T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A(+) T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6 (GFP/GFP) Apoe (-/-) IL-17A(+) T cells into the aortas of Apoe (-/-) recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A(+)TCRγδ(+) T-cell recruitment into atherosclerotic lesions. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of a physical activity programme in the aquatic environment on haemodynamic constants in pregnant women.

PubMed

Vázquez-Lara, Juana María; Ruiz-Frutos, Carlos; Rodríguez-Díaz, Luciano; Ramírez-Rodrigo, Jesús; Villaverde-Gutiérrez, Carmen; Torres-Luque, Gema

2017-09-20

To evaluate the effect of a physical activity programme in the aquatic environment with immersion up to the neck, of six weeks duration, on haemodynamic constants in pregnant women. A six-week physical activity programme in the aquatic environment was carried out with a total of 46 pregnant women, who were distributed into an experimental group (n = 18), which participated in the programme, and a control group (n = 28), which followed routine care. In both groups different haemodynamic measurements were evaluated before and after the program. At the beginning of the programme the mean systolic blood pressure was similar between groups, but diastolic blood pressure was slightly higher in the experimental group. When the measurements at the last session were compared, arterial pressures (systolic, diastolic and mean) were significantly higher in the control group (p <.050). Similarly, the initial plasma volume values did not differ between groups, but after the intervention, the control group women showed a higher mean (p <.010). The fraction of sodium excretion (FENa) increased significantly in the experimental group, after the programme, with a mean three times higher (p <.050). Aldosterone plasma levels did not show significant differences between the groups in the different measurements. A programme of swimming and immersion exercises in pregnant women contributes to hydrosaline balance, preventing an excessive increase in usual plasma volume during pregnancy and in the activity of the renin-aldosterone axis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jing-Hsien; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; Tsai, Chia-Wen

Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foammore » cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.« less

Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization

PubMed Central

Zhang, Zong-Kang; Li, Jie; Yan, De-Xin; Leung, Wing-Nang; Zhang, Bao-Ting

2016-01-01

Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg−1·day−1) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques. PMID:26828485

Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Ikuko, E-mail: nakamuri@riken.jp; Department of Cardiovascular Medicine, Saga University, Saga; Hasegawa, Koki

2013-03-29

Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectinmore » mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

Effect of impaired glucose tolerance on atherosclerotic lesion formation: an evaluation in selectively bred mice with different susceptibilities to glucose intolerance.

PubMed

Asai, Akira; Nagao, Mototsugu; Kawahara, Momoyo; Shuto, Yuki; Sugihara, Hitoshi; Oikawa, Shinichi

2013-12-01

Impaired glucose tolerance (IGT) is an independent risk factor for atherosclerotic cardiovascular disease. However, due to the lack of appropriate animal models, the underlying mechanisms for IGT-induced atherosclerosis remain to be elucidated in vivo. We recently used selective breeding to establish 2 mouse lines with distinctively different susceptibilities to diet-induced glucose intolerance, designated selectively bred diet-induced glucose intolerance-resistant (SDG-R) and SDG-prone (SDG-P), respectively. Here, we assessed atherosclerotic lesion formation in these mice. Female SDG-R and SDG-P mice were fed an atherogenic diet (AD; 1.25% cholesterol, 0.5% sodium cholate, and 36% energy as fat) for 20 weeks (8-28 weeks of age). Oral glucose tolerance tests were performed during the AD-feeding period. Atherosclerotic lesion formation was quantitatively analyzed in serial aortic sinus sections by oil red O staining. Plasma lipids were measured after the AD-feeding period. Glucose tolerance was impaired in SDG-P mice as compared to SDG-R mice over the 20-week AD-feeding period. No significant differences were observed in any plasma lipid measurement between the 2 mouse lines. Aortic sinus atherosclerotic lesion formation in SDG-P mice was approximately 4-fold greater than that in SDG-R mice. In 2 mouse lines with different susceptibilities to diet-induced glucose intolerance, IGT accelerated atherosclerotic lesion formation. These mice may therefore serve as useful in vivo models for investigating the causal role of IGT in the pathogenesis of atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

PubMed

Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

2017-09-28

Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among

HDL mimetic CER-001 targets atherosclerotic plaques in patients.

PubMed

Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

2016-08-01

Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p < 0.001). Using serial PET/CT imaging, we showed that arterial uptake of CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p < 0.001). Plaque TBRmax correlated with local plaque contrast enhancement (r = 0.56; p = 0.019) as assessed by CE-MRI. Infusion of HDL mimetic CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http

Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice.

PubMed

Schroeter, Marco R; Humboldt, Tim; Schäfer, Katrin; Konstantinides, Stavros

2009-07-01

Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.

In-Vivo Fluorescence Spectroscopy Of Normal And Atherosclerotic Arteries

NASA Astrophysics Data System (ADS)

Deckelbaum, Lawrence I.; Sarembock, Ian J.; Stetz, Mark L.; O'Brien, Kenneth M.; Cutruzzola, Francis W.; Gmitro, Arthur F.; Ezekowitz, Michael D.

1988-06-01

Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal arteries in-vitro and may thus potentially guide laser angioplasty. To evaluate the feasibility of laser-induced fluorescence spectroscopy in a living blood-filled arterial system we performed fiberoptic laser-induced fluorescence spectroscopy in a rabbit model of focal femoral atherosclerosis. A laser-induced fluorescence spectroscopy score was derived from stepwise linear regression analysis of in-vitro spectra to distinguish normal aorta (score>0) from atherosclerotic femoral artery (score<0). A 400 u silica fiber, coupled to a helium cadmium laser and optical multichannel analyzer, was inserted through a 5F catheter to induce and record in-vivo fluorescence from femoral and aortoiliac arteries. Arterial spectra could be recorded in all animals (n=10: 5 occlusions, 5 stenoses). Blood spectra were of low intensity and were easily distinguished from arterial spectra. The scores (mean ± SEM) for the in-vivo spectra were -0.69 +/- 0.29 for artherosclerotic femoral, and +0.54 ±. 0.15 for normal aorta (p<.01 p=NS compared to in-vitro spectra). In-vitro, a fiber tip to tissue distance <50 u was necessary for adequate arterial LIFS in blood. At larger distances low intensity blood spectra were recorded (1/20 the intensity of tissue spectra). Thus, fiberoptic laser-induced fluorescence spectroscopy can be sucessfully performed in a blood filled artery provided the fiber tip is approximated to the tissue.

[Expression and antagonist role of endothelin and nitric oxide synthase in atherosclerotic plaque].

PubMed

Song, L; Wang, D; Wang, T

1997-02-01

To study the pathogenetic mechanism of atherosclerotic plaque, the action of mediation and antagonism of endothelin (ET) and nitric oxide synthase (NOS) was investigated. In situ hybridization, RT-PCR on endothelin and NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model and cultured vascular smooth muscle cells (VSMC) from normal rabbit. Transcription of endothelin mRNA increased and transcription of NOS mRNA decreased in astherosclerotic plaque: compared with normal aorta, expression of ET gene in plaque was increased by 1.2 times and the expression of NOS gene was decreased by 22.2%; cytochemistry combined with image pattern analysis showed that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist of ET could inhibit the role of ET which causes a decrease of NOS protein in VSMC. The imbalance between NOS and ET, namely abnormal increase of ET and/or obvious decrease of NOS, is related to atherosclerotic plaque formation.

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

PubMed Central

Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

1987-01-01

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries.

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Lord, Reginald S A

2008-08-01

The mechanisms of ectopic bone formation in arteries are poorly understood. Osteoblasts might originate either from stem cells that penetrate atherosclerotic plaques from the blood stream or from pluripotent mesenchymal cells that have remained in the arterial wall from embryonic stages of the development. We have examined the frequency of the expression and spatial distribution of osteoblast-specific factor-2/core binding factor-1 (Osf2/Cbfa1) in carotid and coronary arteries. Cbfa1-expressing cells were rarely observed but were found in all tissue specimens in the deep portions of atherosclerotic plaques under the necrotic cores. The deep portions of atherosclerotic plaques under the necrotic cores were characterized by the lack of capillaries of neovascularization. In contrast, plaque shoulders, which were enriched by plexuses of neovascularization, lacked Cbfa1-expressing cells. No bone formation was found in any of the 21 carotid plaques examined and ectopic bone was observed in only two of 12 coronary plaques. We speculate that the sparse invasion of sprouts of neovascularization into areas underlying the necrotic cores, where Cbfa1-expressing cells reside, might explain the rarity of events of ectopic bone formation in the arterial wall. This study has also revealed that Cbfa1-expressing cells contain alpha-smooth muscle actin and myofilaments, indicating their relationship with arterial smooth muscle cells.

Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study.

PubMed

Ye, Zusen; Zhang, Zhizhong; Zhang, Hao; Hao, Yonggang; Zhang, Jun; Liu, Wenhua; Xu, Gelin; Liu, Xinfeng

2017-03-01

Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events. Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan-Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively. A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males. Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Deficiency of Endogenous Acute Phase Serum Amyloid A Does Not Impact Atherosclerotic Lesions in ApoE-/- Mice

PubMed Central

De Beer, Maria C; Wroblewski, Joanne M; Noffsinger, Victoria P; Rateri, Debra L; Howatt, Deborah A; Balakrishnan, Anju; Ji, Ailing; Shridas, Preetha; Thompson, Joel C; van der Westhuyzen, Deneys R; Tannock, Lisa R; Daugherty, Alan; Webb, Nancy R; De Beer, Frederick C

2014-01-01

Objective Although elevated plasma concentrations of serum amyloid A (SAA) are strongly associated with increased risk for atherosclerotic cardiovascular disease in humans, the role of SAA in the pathogenesis of lesion formation remains obscure. Our goal was to determine the impact of SAA deficiency on atherosclerosis in hypercholesterolemic mice. Approach and Results ApoE-/- mice, either wild type or deficient in both major acute phase SAA isoforms, SAA1.1 and SAA2.1 (SAAWT and SAAKO, respectively), were fed a normal rodent diet for 50 weeks. Female, but not male SAAKO mice had a modest increase (22%; p ≤ 0.05) in plasma cholesterol concentrations and a 53% increase in adipose mass compared to SAAWT mice that did not impact the plasma cytokine levels or the expression of adipose tissue inflammatory markers. SAA deficiency did not impact lipoprotein cholesterol distributions or plasma triglyceride concentrations in either male or female mice. Atherosclerotic lesion areas measured on the intimal surfaces of the arch, thoracic, and abdominal regions were not significantly different between SAAKO and SAAWT mice in either gender. To accelerate lesion formation, mice were fed a Western diet for 12 weeks. SAA deficiency had no effect on diet-induced alterations in plasma cholesterol, triglyceride or cytokine concentrationsn or on aortic atherosclerotic lesion areas in either male or female mice. In addition, SAA deficiency in male mice had no effect on lesion areas or macrophage accumulation in the aortic roots. Conclusions The absence of endogenous SAA1.1 and 2.1 does not impact atherosclerotic lipid deposition in apoE-/- mice fed either normal or Western diets. PMID:24265416

Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

PubMed Central

Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

2017-01-01

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

Heparin Cofactor II in Atherosclerotic Lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study

PubMed Central

Rau, Jill C.; Deans, Carolyn; Hoffman, Maureane R.; Thomas, David B.; Malcom, Gray T.; Zieske, Arthur W.; Strong, Jack P.; Koch, Gary G.; Church, Frank C.

2009-01-01

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma. PMID:19747479

Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics (CFD): presentation of a patient-specific method combining magnetic resonance imaging and numerical simulations.

PubMed

Midulla, Marco; Moreno, Ramiro; Baali, Adil; Chau, Ming; Negre-Salvayre, Anne; Nicoud, Franck; Pruvo, Jean-Pierre; Haulon, Stephan; Rousseau, Hervé

2012-10-01

In the last decade, there was been increasing interest in finding imaging techniques able to provide a functional vascular imaging of the thoracic aorta. The purpose of this paper is to present an imaging method combining magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain a patient-specific haemodynamic analysis of patients treated by thoracic endovascular aortic repair (TEVAR). MRI was used to obtain boundary conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences which covered the whole thoracic aorta. Phase contrast imaging provided the inlet and outlet profiles. A CFD mesh generator was used to model the arterial morphology, and wall movements were imposed according to the cine imaging. CFD runs were processed using the finite volume (FV) method assuming blood as a homogeneous Newtonian fluid. Twenty patients (14 men; mean age 62.2 years) with different aortic lesions were evaluated. Four-dimensional mapping of velocity and wall shear stress were obtained, depicting different patterns of flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress in-stent and along the native aorta. A computational method using a combined approach with MRI appears feasible and seems promising to provide detailed functional analysis of thoracic aorta after stent-graft implantation. • Functional vascular imaging of the thoracic aorta offers new diagnostic opportunities • CFD can model vascular haemodynamics for clinical aortic problems • Combining CFD with MRI offers patient specific method of aortic analysis • Haemodynamic analysis of stent-grafts could improve clinical management and follow-up.

Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits

PubMed Central

2010-01-01

Background Piper sarmentosum (P.s) has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically. Aim The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits. Methods Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study. Results Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 ± 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 ± 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups. Conclusion Administration of P.s extract has protective effect against atheroscleros PMID:20433693

Angiographic assessment of atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy.

PubMed

Çildağ, Mehmet B; Ertuğrul, Bülent M; Köseoğlu, Ömer Fk; Çildağ, Songül; Armstrong, David G

2018-06-01

The aim of this study was to investigate atherosclerotic load at the lower extremity in patients with diabetic foot and charcot neuro-arthropathy and compare them with patients with diabetic foot without charcot neuro-arthropathy. This retrospective study consists of 78 patients with diabetic foot who had lower extremity angiography with antegrade approach. All patients were classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the side of diabetic foot was determined by using the Bollinger angiogram scoring method. Comparison of atherosclerotic load between the two groups was performed. The mean of total and infrapopliteal level angiogram scoring of all patients was 33.3 (standard deviation, sd:±17.2) and 29.3 (sd:±15.6), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:±11.6) and 15.7 (sd:±10.4), respectively. The mean of total and infrapopliteal level angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group was 42.8 (sd:±12.7) and 37.7 (sd:±12.0), respectively. There was a statistically significant difference between the two groups of mean total and infrapopliteal angiogram scoring (p < 0.01). This angiographic study confirms that the atherosclerotic load in patients with diabetic foot and chronic charcot neuro-arthropathy is significantly less than in patients with neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy. Copyright © 2017. Published by Elsevier Taiwan LLC.

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture

PubMed Central

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-01-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 μm) and presumably stable plaques, in which fibrous caps were thicker than 100 μm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908±0.544 versus 6.208±0.467 matrix vesicles per 1.92 μm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles

Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture.

PubMed

Bobryshev, Y V; Killingsworth, M C; Lord, R S A; Grabs, A J

2008-10-01

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles

Age-dependent effects of milrinone and levosimendan on ventricular function and haemodynamics in newborn and mature pigs.

PubMed

Hyldebrandt, Janus A; Larsen, Signe H; Schmidt, Michael R; Hjortdal, Vibeke E; Ravn, Hanne B

2011-10-01

Inodilators are used in the treatment of low cardiac output, mainly after cardiac surgery. At present, there is little knowledge of the effect of inodilators in the newborn heart. Immediately after birth and in the neonatal period, the metabolism and physiology of the heart undergo major changes. We hypothesised that effects of the inodilators milrinone and levosimendan on myocardial contractility and haemodynamics under normal physiological conditions were age dependent. Animal studies were conducted on 48 pigs using a closed-chest biventricular conductance catheter method. Pigs in two age groups, that is, 5-6 days and 5-6 weeks, were assigned to milrinone, levosimendan, or a control group. We observed that both milrinone - 19.2% with a p value of 0.05 - and levosimendan - 25.7% with a p value of 0.03 compared with the control group increased cardiac output, as well as myocardial contractility with a maximum pressure development over time: milrinone 28.2%, p = 0.01 and levosimendan 19.4%, p = 0.05. Milrinone improved diastolic performance (p < 0.05) in the left ventricle in the 5-6-week-old animals. In the newborn animals, neither of the inodilators increased ventricular contractility or cardiac output; however, we observed a significant decrease in the mean arterial pressure: milrinone 34.6%, p < 0.01 and levosimendan 30.1%, p = 0.02. Both inodilators demonstrated age-dependent haemodynamic effects, and it is noteworthy that neither milrinone nor levosimendan was able to increase cardiac output in the newborn heart.

Non-linear imaging and characterization of atherosclerotic arterial tissue using combined two photon fluorescence, second-harmonic generation and CARS microscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Matthäus, Christian; Meyer, Tobias; Lattermann, Annika; Dietzek, Benjamin; Brehm, Bernhard R.; Popp, Jürgen; Pavone, Francesco S.

2014-02-01

Atherosclerosis is among the most widespread cardiovascular diseases and one of the leading cause of death in the Western World. Characterization of arterial tissue in atherosclerotic condition is extremely interesting from the diagnostic point of view. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires a morpho-functional approach. Multimodal non-linear microscopy has the potential to bridge this gap by providing morpho-functional information on the examined tissues in a label-free way. Here we employed multiple non-linear microscopy techniques, including CARS, TPF, and SHG to provide intrinsic optical contrast from various tissue components in both arterial wall and atherosclerotic plaques. CARS and TPF microscopy were used to respectively image lipid depositions within plaques and elastin in the arterial wall. Cholesterol deposition in the lumen and collagen in the arterial wall were selectively imaged by SHG microscopy and distinguished by forward-backward SHG ratio. Image pattern analysis allowed characterizing collagen organization in different tissue regions. Different values of fiber mean size, distribution and anisotropy are calculated for lumen and media prospectively allowing for automated classification of atherosclerotic lesions. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue and has the potential to find a stable place in clinical setting as well as to be applied in vivo in the near future.

Expressions of Mast Cell Tryptase and Brain Natriuretic Peptide in Myocardium of Sudden Death due to Hypersensitivity and Coronary Atherosclerotic Heart Disease.

PubMed

Shi, J R; Tian, C J; Zeng, Q; Guo, X J; Lu, J; Gao, C R

2016-06-01

To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting. Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （ P <0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （ P <0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （ P >0.05）. The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

Potential Anti-Atherosclerotic Properties of Astaxanthin.

PubMed

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-02-05

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Potential Anti-Atherosclerotic Properties of Astaxanthin

PubMed Central

Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

2016-01-01

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

Apoptosis does not mediate macrophage depletion in rabbit atherosclerotic plaques after dietary lipid lowering.

PubMed

Martinet, Wim; Croons, Valerie; Herman, Arnold G; De Meyer, Guido R Y

2009-08-01

Unstable atherosclerotic plaques are characterized by a thin fibrous cap that contains few smooth muscle cells (SMCs) and numerous foam cells of macrophage origin. Previously we and others demonstrated that macrophages disappear from atherosclerotic plaques after dietary lipid lowering. However, it remains unclear whether loss of macrophages after lipid lowering occurs via increased apoptosis, decreased macrophage replication and/or recruitment, or via a combination of both. Rabbits were fed a diet supplemented with cholesterol (0.3%) for 24 weeks followed by a normal diet for 4, 12, or 24 weeks. After 24 weeks of cholesterol supplement, plaques showed apoptosis in both macrophages and SMCs, as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Cell replication (Ki-67 immunolabeling) was predominantly present in macrophages. After 24 weeks of cholesterol withdrawal, the thickness and areas of the plaques were unchanged. Nevertheless, plaques showed a considerable loss of macrophages. This event was associated with a reduced immunoreactivity for vascular cell adhesion molecule-1 (VCAM-1) in the endothelial cells starting 4 weeks after cholesterol withdrawal. Apoptosis did not increase after lipid lowering but showed a steady decline. Apart from decreased VCAM-1 expression, a strong decrease in Ki-67 immunolabeling was observed after 12 weeks of cholesterol withdrawal. Our findings suggest that loss of macrophages in atherosclerotic plaques after dietary lipid lowering is not related to induction of macrophage apoptosis but mainly a consequence of impaired monocyte recruitment followed by decreased macrophage replication. This information is essential for understanding the effects of aggressive lipid lowering on plaque stability.

12- and 15-lipoxygenases in human carotid atherosclerotic lesions: Associations with cerebrovascular symptoms

USDA-ARS?s Scientific Manuscript database

Lipoxygenase (ALOX) enzymes are implicated in both pro- and anti-atherogenic processes. The aim of this study was to investigate mRNA expression of 12- and 15-lipoxygenases (ALOX12, ALOX12B, ALOX15, ALOX15B) and the atypical ALOXE3 in human carotid atherosclerotic lesions, in relation to cerebrovasc...

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

PubMed

Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

NASA Astrophysics Data System (ADS)

Evani, Shankar J.; Ramasubramanian, Anand K.

2016-01-01

Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

Grating interferometry-based phase microtomography of atherosclerotic human arteries

NASA Astrophysics Data System (ADS)

Buscema, Marzia; Holme, Margaret N.; Deyhle, Hans; Schulz, Georg; Schmitz, Rüdiger; Thalmann, Peter; Hieber, Simone E.; Chicherova, Natalia; Cattin, Philippe C.; Beckmann, Felix; Herzen, Julia; Weitkamp, Timm; Saxer, Till; Müller, Bert

2014-09-01

Cardiovascular diseases are the number one cause of death and morbidity in the world. Understanding disease development in terms of lumen morphology and tissue composition of constricted arteries is essential to improve treatment and patient outcome. X-ray tomography provides non-destructive three-dimensional data with micrometer-resolution. However, a common problem is simultaneous visualization of soft and hard tissue-containing specimens, such as atherosclerotic human coronary arteries. Unlike absorption based techniques, where X-ray absorption strongly depends on atomic number and tissue density, phase contrast methods such as grating interferometry have significant advantages as the phase shift is only a linear function of the atomic number. We demonstrate that grating interferometry-based phase tomography is a powerful method to three-dimensionally visualize a variety of anatomical features in atherosclerotic human coronary arteries, including plaque, muscle, fat, and connective tissue. Three formalin-fixed, human coronary arteries were measured using advanced laboratory μCT. While this technique gives information about plaque morphology, it is impossible to extract the lumen morphology. Therefore, selected regions were measured using grating based phase tomography, sinograms were treated with a wavelet-Fourier filter to remove ring artifacts, and reconstructed data were processed to allow extraction of vessel lumen morphology. Phase tomography data in combination with conventional laboratory μCT data of the same specimen shows potential, through use of a joint histogram, to identify more tissue types than either technique alone. Such phase tomography data was also rigidly registered to subsequently decalcified arteries that were histologically sectioned, although the quality of registration was insufficient for joint histogram analysis.

Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease

PubMed Central

Horseman, Michael A.; Surani, Salim; Bowman, John D.

2017-01-01

Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or con-tributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmen-tal microbes that are in part modulated through a series of receptors known as toll-like receptors. Endo-toxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogen-esis of atherosclerotic heart disease. Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in athero-sclerotic disease prevention and treatment.

Usefulness of automatic measurement of contrast flow intensity: an innovative tool in contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization. A pilot study.

PubMed

Lisowska, A; Knapp, M; Tycinska, A; Sawicki, R; Kralisz, P; Lisowski, P; Sobkowicz, B; Musial, W I

2014-02-01

Contrast-enhanced ultrasound imaging of the carotid arteries (CECU) permits direct, real-time visualization of neovascularization in atherosclerotic plaques and is a confirmed predictor of unstable atheromatous lesions. The aim of the study was the assessment of a new, automatically measured index of intensity in quantitative estimation of the contrast flow through the carotid plaque (till now assessed only visually). Forty-four patients (mean age 70.4±11.4) with ultrasound diagnosed significant stenosis of internal carotid artery (ICA), after cerebrovascular or cardiovascular events, qualified for carotid artery stenting (CAS) were examined. The carotid ultrasound examinations with contrast agent Sonovue were performed. Visually in 22 patients (50%) contrast flow through the atherosclerotic plaques was found. In 17 patients (38.6%) massive, calcified atherosclerotic plaques were present. Patients with preserved contrast flow through the plaque more frequently had a history of cerebral stroke (P=0.04). Massive calcifications of atherosclerotic plaques correlated with a previous MI (P=0.03) and the degree of advancement of coronary artery disease (P=0.04), but not with a previous cerebral stroke. Contrast flow through the atherosclerotic plaque positively correlated with values of the index of intensity (r=0.69, P<0.00001). In patients with preserved contrast flow the mean value of the index of intensity was 22.24±3.55 dB as compared with 12.37±7.67 dB - a value present in patients without preserved contrast flow. No significant relation for the degree of calcifications and the value of the index of intensity was found. The assessment of the index of intensity is a novel, simple and automatic method to estimate the degree of contrast flow through the carotid plaque. The values of the index of intensity correlate with the contrast flow through the atherosclerotic plaque, but not with its calcification.

Acute resistance exercise with blood flow restriction in elderly hypertensive women: haemodynamic, rating of perceived exertion and blood lactate.

PubMed

Pinto, Roberta R; Karabulut, Murat; Poton, Roberto; Polito, Marcos D

2018-01-01

This study aimed to compare haemodynamic, rating of perceived exertion and blood lactate responses during resistance exercise with blood flow restriction (BFR) compared with traditional high-intensity resistance exercise in hypertensive older women. Eighteen hypertensive women (age = 67·0 ± 1·7 years.) undertook three random sessions: (i) three sets; 10 repetitions; 20% of one repetition maximum (1RM) with BFR; (ii) three sets; 10 repetitions; 65% of 1RM; without BFR; and (iii) no-exercise with BFR. The exercise sessions were performed on knee extension equipment. Systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV) and cardiac output (CO) were significantly higher (P<0·05) in all sets of exercise sessions than the control. No statistically significant differences were detected between exercise sessions. However, SBP, DBP and systemic vascular resistance were higher (P<0·05) and SV and CO were lower (P<0·05) during the rest intervals in the session with BFR. The perceived exertion was significantly higher (P<0·01) in the 1st (4·8 ± 0·4 versus 3·1 ± 0·3), 2nd (7·3 ± 0·4 versus 5·7 ± 0·4) and 3rd sets (8·6 ± 0·5 versus 7·5 ± 0·4) of the traditional high-intensity resistance exercise compared with the exercise with BFR. Blood lactate was higher (P<0·05) in the traditional high-intensity resistance exercise (6·2 ± 0·7 mmol) than in the exercise with BFR (4·5 ± 0·4 mmol). In comparison with high-intensity resistance exercise, low-intensity resistance exercise with BFR can elicit: (i) same haemodynamic values during exercise; (ii) lower rating of perceived exertion; (iii) lower blood lactate; (iv) higher haemodynamic demand during the rest intervals. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic Plaque Formation Reveals Osteoclast-specific Protein Expression.

PubMed

Wierer, Michael; Prestel, Matthias; Schiller, Herbert B; Yan, Guangyao; Schaab, Christoph; Azghandi, Sepiede; Werner, Julia; Kessler, Thorsten; Malik, Rainer; Murgia, Marta; Aherrahrou, Zouhair; Schunkert, Heribert; Dichgans, Martin; Mann, Matthias

2018-02-01

Atherosclerosis leads to vascular lesions that involve major rearrangements of the vascular proteome, especially of the extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation of plaques by single-run, high-resolution mass spectrometry (MS)-based proteomics. To probe localization on a proteome-wide scale we employed quantitative detergent solubility profiling. This compartment- and time-resolved resource of atherogenesis comprised 5117 proteins, 182 of which changed their expression status in response to vessel maturation and atherosclerotic plaque development. In the insoluble ECM proteome, 65 proteins significantly changed, including relevant collagens, matrix metalloproteinases and macrophage derived proteins. Among novel factors in atherosclerosis, we identified matrilin-2, the collagen IV crosslinking enzyme peroxidasin as well as the poorly characterized MAM-domain containing 2 (Mamdc2) protein as being up-regulated in the ECM during atherogenesis. Intriguingly, three subunits of the osteoclast specific V-ATPase complex were strongly increased in mature plaques with an enrichment in macrophages thus implying an active de-mineralization function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic Plaque Formation Reveals Osteoclast-specific Protein Expression*

PubMed Central

Wierer, Michael; Prestel, Matthias; Schiller, Herbert B.; Yan, Guangyao; Schaab, Christoph; Azghandi, Sepiede; Werner, Julia; Kessler, Thorsten; Malik, Rainer; Murgia, Marta; Aherrahrou, Zouhair; Schunkert, Heribert; Dichgans, Martin; Mann, Matthias

2018-01-01

Atherosclerosis leads to vascular lesions that involve major rearrangements of the vascular proteome, especially of the extracellular matrix (ECM). Using single aortas from ApoE knock out mice, we quantified formation of plaques by single-run, high-resolution mass spectrometry (MS)-based proteomics. To probe localization on a proteome-wide scale we employed quantitative detergent solubility profiling. This compartment- and time-resolved resource of atherogenesis comprised 5117 proteins, 182 of which changed their expression status in response to vessel maturation and atherosclerotic plaque development. In the insoluble ECM proteome, 65 proteins significantly changed, including relevant collagens, matrix metalloproteinases and macrophage derived proteins. Among novel factors in atherosclerosis, we identified matrilin-2, the collagen IV crosslinking enzyme peroxidasin as well as the poorly characterized MAM-domain containing 2 (Mamdc2) protein as being up-regulated in the ECM during atherogenesis. Intriguingly, three subunits of the osteoclast specific V-ATPase complex were strongly increased in mature plaques with an enrichment in macrophages thus implying an active de-mineralization function. PMID:29208753

Association of CD147 genetic polymorphisms with carotid atherosclerotic plaques in a Han Chinese population with cerebral infarction.

PubMed

Ni, Tongtian; Chen, Min; Yang, Kang; Shao, Jianwei; Fu, Yi; Zhou, Weijun

2017-08-01

Given the important role of CD147 in the development of atherosclerosis, we speculated that CD147 genetic polymorphisms might influence the formation of carotid atherosclerotic plaques. The study was to investigate the association between CD147 gene polymorphisms and susceptibility to carotid atherosclerotic plaques in individuals with cerebral infarction (CI). Eight SNPs in the regulatory and coding regions of the CD147 gene were examined using polymerase chain reaction-ligase detection reaction (PCR-LDR) in DNA samples from 732 Chinese patients with CI, divided into a carotid plaque group (n=475) and a non-carotid plaque group (n=257). Significant differences were found in the genotypes and allele frequencies of the rs4919862 SNP between the carotid plaque and non-carotid plaque groups of CI patients (P<0.05), while the frequencies of the C allele and the CC genotype in the non-carotid plaque group were significantly lower than those in the carotid plaque group, and the frequencies of the T allele in the non-carotid plaque group were significantly higher than those in the carotid plaque group (P<0.05). In addition, there was strong linkage disequilibrium among the rs4919862, rs8637 and rs8259 sites. In a haplotype analysis, the occurrence rate of the haplotype GATGCAGC was 2.095 times higher in the carotid plaque group than in the non-carotid plaque group (P<0.05). These results showed that the rs4919862 SNP of CD147 was closely associated with carotid atherosclerotic plaques formation. Thus, polymorphisms of the CD147 gene may be related to the tendency for carotid atherosclerotic plaques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging of lipids in atherosclerotic lesion in aorta from ApoE/LDLR-/- mice by FT-IR spectroscopy and Hierarchical Cluster Analysis.

PubMed

P Wrobel, Tomasz; Mateuszuk, Lukasz; Chlopicki, Stefan; Malek, Kamilla; Baranska, Malgorzata

2011-12-21

Spectroscopy-based approaches can provide an insight into the biochemical composition of a tissue sample. In the present work Fourier transform infrared (FT-IR) spectroscopy was used to develop a reliable methodology to study the content of free fatty acids, triglycerides, cholesteryl esters as well as cholesterol in aorta from mice with atherosclerosis (ApoE/LDLR(-/-) mice). In particular, distribution and concentration of palmitic, oleic and linoleic acid derivatives were analyzed. Spectral analysis of pure compounds allowed for clear discrimination between free fatty acids and other similar moieties based on the carbonyl band position (1699-1710 cm(-1) range). In order to distinguish cholesteryl esters from triglycerides a ratio of carbonyl band to signal at 1010 cm(-1) was used. Imaging of lipids in atherosclerotic aortic lesions in ApoE/LDLR(-/-) mice was followed by Hierarchical Cluster Analysis (HCA). The aorta from C57Bl/6J control mice (fed with chow diet) was used for comparison. The measurements were completed with an FT-IR spectrometer equipped with a 128 × 128 FPA detector. In cross-section of aorta from ApoE/LDLR(-/-) mice a region of atherosclerotic plaque was clearly identified by HCA, which was later divided into 2 sub-regions, one characterized by the higher content of cholesterol, while the other by higher contents of cholesteryl esters. HCA of tissues deposited on normal microscopic glass, hence limited to the 2200-3800 cm(-1) spectral range, also identified a region of atherosclerotic plaque. Importantly, this region correlates with the area stained by standard histological staining for atherosclerotic plaque (Oil Red O). In conclusion, the use of FT-IR and HCA may provide a novel tool for qualitative and quantitative analysis of contents and distribution of lipids in atherosclerotic plaque.

Diagnosis of vulnerable atherosclerotic plaques by time-resolved fluorescence spectroscopy and ultrasound imaging.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Shung, K K; Sun, L; Marcu, L

2006-01-01

In this study, time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonography were applied to detect vulnerable (high-risk) atherosclerotic plaque. A total of 813 TR-LIFS measurements were taken from carotid plaques of 65 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified by histopathology as thin, fibrotic, calcified, low-inflamed, inflamed and necrotic lesions. Spectral and time-resolved parameters (normalized intensity values and Laguerre expansion coefficients) were extracted from the TR-LIFS data. Feature selection for classification was performed by either analysis of variance (ANOVA) or principal component analysis (PCA). A stepwise linear discriminant analysis algorithm was developed for detecting inflamed and necrotic lesion, representing the most vulnerable plaques. These vulnerable plaques were detected with high sensitivity (>80%) and specificity (>90%). Ultrasound (US) imaging was obtained in 4 carotid plaques in addition to TR-LIFS examination. Preliminary results indicate that US provides important structural information of the plaques that could be combined with the compositional information obtained by TR-LIFS, to obtain a more accurate diagnosis of vulnerable atherosclerotic plaque.

NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation.

PubMed

Plotkin, Jesse D; Elias, Michael G; Dellinger, Anthony L; Kepley, Christopher L

2017-08-01

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Cadmium exposure and atherosclerotic carotid plaques –Results from the Malmö diet and Cancer study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se; Barregard, Lars, E-mail: lars.barregard@amm.gu.se; Sallsten, Gerd, E-mail: gerd.sallsten@amm.gu.se

Background: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. Objectives: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. Methods: A population sample of 4639 Swedish middle-aged women and men was examined in 1991–1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. Results: Comparing quartile 4 with quartile 1 of blood cadmium,more » the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6–2.2) after adjustment for sex and, age; 1.4 (1.1–1.8) after additional adjustment for smoking status; 1.4 (1.1–1.7) after the addition of education level and life style factors; 1.3 (1.03–1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0–2.1) and 1.4 (0.9–2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. Conclusions: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure. - Highlights: • Blood cadmium level is associated with atherosclerotic plaques in the carotid artery. • The results extend previous knowledge of cadmium exposure and clinical events. • The role of smoking remains unclear.« less

Haemodynamic effects of adrenaline (epinephrine) depend on chest compression quality during cardiopulmonary resuscitation in pigs.

PubMed

Pytte, Morten; Kramer-Johansen, Jo; Eilevstjønn, Joar; Eriksen, Morten; Strømme, Taevje A; Godang, Kristin; Wik, Lars; Steen, Petter Andreas; Sunde, Kjetil

2006-12-01

Adrenaline (epinephrine) is used during cardiopulmonary resuscitation (CPR) based on animal experiments without supportive clinical data. Clinically CPR was reported recently to have much poorer quality than expected from international guidelines and what is generally done in laboratory experiments. We have studied the haemodynamic effects of adrenaline during CPR with good laboratory quality and with quality simulating clinical findings and the feasibility of monitoring these effects through VF waveform analysis. After 4 min of cardiac arrest, followed by 4 min of basic life support, 14 pigs were randomised to ClinicalCPR (intermittent manual chest compressions, compression-to-ventilation ratio 15:2, compression depth 30-38 mm) or LabCPR (continuous mechanical chest compressions, 12 ventilations/min, compression depth 45 mm). Adrenaline 0.02 mg/kg was administered 30 s thereafter. Plasma adrenaline concentration peaked earlier with LabCPR than with ClinicalCPR, median (range), 90 (30, 150) versus 150 (90, 270) s (p = 0.007), respectively. Coronary perfusion pressure (CPP) and cortical cerebral blood flow (CCBF) increased and femoral blood flow (FBF) decreased after adrenaline during LabCPR (mean differences (95% CI) CPP 17 (6, 29) mmHg (p = 0.01), FBF -5.0 (-8.8, -1.2) ml min(-1) (p = 0.02) and median difference CCBF 12% of baseline (p = 0.04)). There were no significant effects during ClinicalCPR (mean differences (95% CI) CPP 4.7 (-3.2, 13) mmHg (p = 0.2), FBF -0.2 (-4.6, 4.2) ml min(-1)(p = 0.9) and CCBF 3.6 (-1.8, 9.0)% of baseline (p = 0.15)). Slope VF waveform analysis reflected changes in CPP. Adrenaline improved haemodynamics during laboratory quality CPR in pigs, but not with quality simulating clinically reported CPR performance.

Posture with elevated and extended thorax. The influence of the position on some haemodynamic and ventilatory parameters under general anaesthesia.

PubMed

Videbaek, F

1980-12-01

The effects of a change in posture from flat supine to supine with elevated and extended thorax have been investigated in 12 healthy patients under general anaesthesia prior to elective surgery on the stomach. The following parameters were measured: pulse rate, mean arterial blood pressure (MABP), central venous pressure (CVP), ventilation pressure, oesophageal pressure, and arterial oxygen and carbon dioxide tensions. Changes were measured as deviations from initial values before the change of position at 4 and 15 min after the change. One patient (8%) had a 31% fall in MABP and a 87% fall in CVP, requiring treatment outside the standard procedure, but acceptable values were obtained by simple means. Eleven patients showed only minor changes: a mean initial rise in pulse rate of 10% and a fall in CVP of 25%, after which the pulse rate returned to the initial level and the CVP remained stable. MABP was unchanged, as were ventilation pressure, oesophageal pressure and gas tensions. On the basis of reports in the literature and findings in this study, it is concluded that otherwise healthy patients tolerate the posture well, the slight risk of haemodynamic complications being outweighed by the surgical advantages. This posture should be used with caution in patients who may be haemodynamically unable to compensate.

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

PubMed Central

Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Mathematical modeling of atherosclerotic plaque destabilization: Role of neovascularization and intraplaque hemorrhage.

PubMed

Guo, Muyi; Cai, Yan; Yao, Xinke; Li, Zhiyong

2018-08-07

Observational studies have identified angiogenesis from the adventitial vasa vasorum and intraplaque hemorrhage (IPH) as critical factors in atherosclerotic plaque progression and destabilization. Here we propose a mathematical model incorporating intraplaque neovascularization and hemodynamic calculation with plaque destabilization for the quantitative evaluation of the role of neoangiogenesis and IPH in the vulnerable atherosclerotic plaque formation. An angiogenic microvasculature is generated by two-dimensional nine-point discretization of endothelial cell proliferation and migration from the vasa vasorum. Three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemicals (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase) are involved in the plaque progression model, and described by the reaction-diffusion partial differential equations. The hemodynamic calculation of the microcirculation on the generated microvessel network is carried out by coupling the intravascular, interstitial and transvascular flow. The plasma concentration in the interstitial domain is defined as the description of IPH area according to the diffusion and convection with the interstitial fluid flow, as well as the extravascular movement across the leaky vessel wall. The simulation results demonstrate a series of pathophysiological phenomena during the vulnerable progression of an atherosclerotic plaque, including the expanding necrotic core, the exacerbated inflammation, the high microvessel density (MVD) region at the shoulder areas, the transvascular flow through the capillary wall and the IPH. The important role of IPH in the plaque destabilization is evidenced by simulations with varied model parameters. It is found that the IPH can significantly speed up the plaque vulnerability by increasing necrotic core and thinning fibrous cap. In addition, the decreased MVD and vessel permeability may slow down the process of

Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage.

PubMed

Sato, Shoichiro; Uehara, Toshiyuki; Hayakawa, Mikito; Nagatsuka, Kazuyuki; Minematsu, Kazuo; Toyoda, Kazunori

2013-09-15

There is little information about intracranial atherosclerotic disease (ICAD) and extracranial atherosclerotic disease (ECAD) in patients with acute spontaneous intracerebral hemorrhage (ICH). The purpose of the present study was to elucidate the prevalence of and the factors that correlate with ICAD and ECAD in patients with ICH. A total of 274 patients with acute spontaneous ICH were enrolled. ICAD and ECAD (moderate to severe stenosis or occlusion) were mainly assessed by intracranial magnetic resonance angiography and carotid duplex sonography, respectively. Fifty-one patients (19%) had ICAD or ECAD; 32 had ICAD, and 21 had ECAD. On multivariable analyses, age (OR, 1.52; 95% CI, 1.06-2.28 for every 10 years), monocyte count (OR, 1.37; 95% CI, 1.02-1.87 for every 100/mm(3)), hemoglobin A1c (OR, 2.25; 95% CI, 1.08-5.15 for every 1%), and low-density lipoprotein cholesterol levels (OR, 1.23; 95% CI, 1.08-1.42 for every 10mg/dL) were independently associated with ICAD. Age (OR, 2.20; 95% CI, 1.20-4.38 for 10 years) and dyslipidemia (OR, 3.95; 95% CI, 1.01-15.97) were independently associated with ECAD. ICAD and ECAD were detected in approximately one-fifth of patients with spontaneous ICH. Age and dyslipidemia (or lipid profile) were associated with both ICAD and ECAD. Monocyte count and hemoglobin A1c were associated with ICAD. © 2013. Published by Elsevier B.V. All rights reserved.

Progressive Cortical Neuronal Damage and Chronic Hemodynamic Impairment in Atherosclerotic Major Cerebral Artery Disease.

PubMed

Yamauchi, Hiroshi; Kagawa, Shinya; Kishibe, Yoshihiko; Takahashi, Masaaki; Higashi, Tatsuya

2016-06-01

Cross-sectional studies suggest that chronic hemodynamic impairment may cause selective cortical neuronal damage in patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease. The purpose of this longitudinal study was to determine whether the progression of cortical neuronal damage, evaluated as a decrease in central benzodiazepine receptors (BZRs), is associated with hemodynamic impairment at baseline or hemodynamic deterioration during follow-up. We evaluated the distribution of BZRs twice using positron emission tomography and (11)C-flumazenil over time in 80 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease that had no ischemic episodes during follow-up. Using 3D stereotactic surface projections, we quantified abnormal decreases in the BZRs in the cerebral cortex within the middle cerebral artery distribution and correlated changes in the BZR index with the mean hemispheric values of hemodynamic parameters obtained from (15)O gas positron emission tomography. In the hemisphere affected by arterial disease, the BZR index in 40 patients (50%) was increased during follow-up (mean 26±20 months). In multivariable logistic regression analyses, increases in the BZR index were associated with the decreased cerebral blood flow at baseline and an increased oxygen extraction fraction during follow-up. Increases in the oxygen extraction fraction during follow-up were associated with a lack of statin use. In patients with atherosclerotic internal carotid artery or middle cerebral artery disease, the progression of cortical neuronal damage was associated with hemodynamic impairment at baseline and hemodynamic deterioration during follow-up. Statin use may be beneficial against hemodynamic deterioration and therefore neuroprotective. © 2016 American Heart Association, Inc.

Detection of atherosclerotic plaques in ApoE-deficient mice using (99m)Tc-duramycin.

PubMed

Liu, Zhonglin; Larsen, Brandon T; Lerman, Lilach O; Gray, Brian D; Barber, Christy; Hedayat, Ahmad F; Zhao, Ming; Furenlid, Lars R; Pak, Koon Y; Woolfenden, James M

2016-08-01

Apoptosis of macrophages and smooth muscle cells is linked to atherosclerotic plaque destabilization. The apoptotic cascade leads to exposure of phosphatidylethanolamine (PE) on the outer leaflet of the cell membrane, thereby making apoptosis detectable using probes targeting PE. The objective of this study was to exploit capabilities of a PE-specific imaging probe, (99m)Tc-duramycin, in localizing atherosclerotic plaque and assessing plaque evolution in apolipoprotein-E knockout (ApoE(-/-)) mice. Atherosclerosis was induced in ApoE(-/-) mice by feeding an atherogenic diet. (99m)Tc-duramycin images were acquired using a small-animal SPECT imager. Six ApoE(-/-) mice at 20weeks of age (Group I) were imaged and then sacrificed for ex vivo analyses. Six additional ApoE(-/-) mice (Group II) were imaged at 20 and 40weeks of age before sacrifice. Six ApoE wild-type (ApoE(+/+)) mice (Group III) were imaged at 40weeks as controls. Five additional ApoE(-/-) mice (40weeks of age) (Group IV) were imaged with a (99m)Tc-labeled inactive peptide, (99m)Tc-LinDUR, to assess (99m)Tc-duramycin targeting specificity. Focal (99m)Tc-duramycin uptake in the ascending aorta and aortic arch was detected at 20 and 40weeks in the ApoE(-/-) mice but not in ApoE(+/+) mice. (99m)Tc-duramycin uptake in the aortic lesions increased 2.2-fold on quantitative imaging in the ApoE(-/-) mice between 20 and 40weeks. Autoradiographic and histological data indicated significantly increased (99m)Tc-duramycin uptake in the ascending aorta and aortic arch associated with advanced plaques. Quantitative autoradiography showed that the ratio of activity in the aortic arch to descending thoracic aorta, which had no plaques or radioactive uptake, was 2.1 times higher at 40weeks than at 20weeks (6.62±0.89 vs. 3.18±0.29, P<0.01). There was barely detectable focal uptake of (99m)Tc-duramycin in the aortic arch of ApoE(+/+) mice. No detectable (99m)Tc-LinDUR uptake was observed in the aortas of ApoE(-/-) mice. PE

Comparison of haemodynamic responses following different concentrations of adrenaline with and without lignocaine for surgical field infiltration during cleft lip and cleft palate surgery in children.

PubMed

Muthukumar, Marimuthu; Arya, Virendra K; Mathew, Preety J; Sharma, Ramesh K

2012-01-01

Surgical field infiltration with adrenaline is common practice for quality surgical field during cleft lip and palate repair in children. Intravascular absorption of adrenaline infiltration often leads to adverse haemodynamic responses. In this prospective, double-blinded, randomised study the haemodynamic effects, quality of surgical field and postoperative analgesia following surgical field infiltration with different concentrations of adrenaline with and without lignocaine were compared in 100 American Society of Anesthesiologists physical status I children aged six months to seven years undergoing cleft lip/palate surgery. A standard anaesthesia protocol was used and they were randomised into four groups based on solution for infiltration: adrenaline 1:400,000 (group A), adrenaline 1:200,000 (group B), lignocaine + adrenaline 1:400,000 (group C) and lignocaine + adrenaline 1:200,000 (group D). Statistically significant tachycardia and hypertension occurred only in group B as compared to other groups (P <0.001). The peak changes in heart rate and mean arterial pressure following infiltration occurred at 4.3 ± 2.4, 3.8 ± 1.5, 5.7 ± 3.2 and 5.9 ± 4.9 minutes in groups A, B, C and D respectively. Surgical field was comparable among all groups. Postoperative pain scores and rescue analgesic requirements were lesser in the groups where lignocaine was added to the infiltrating solution (P <0.05). We found that 1:400000 or 1:200000 adrenaline with lignocaine 0.5 to 0.7% is most suitable for infiltration in terms of stable haemodynamics, quality of surgical field and good postoperative analgesia in children.

Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension.

PubMed

Bellofiore, Alessandro; Dinges, Eric; Naeije, Robert; Mkrdichian, Hamorabi; Beussink-Nelson, Lauren; Bailey, Melissa; Cuttica, Michael J; Sweis, Ranya; Runo, James R; Keevil, Jon G; Francois, Christopher J; Shah, Sanjiv J; Chesler, Naomi C

2017-03-01

Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH. Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z 0 ), characteristic impedance (Z C , a measure of proximal PA stiffness) and proximal and distal PA compliance (C PA ). In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z C =2.31±0.38 vs 1.33±0.15 WU×m 2 at rest; p=0.003) and PA compliance was decreased (C PA =0.88±0.10 vs 1.32±0.17 mL/mm Hg/m 2 at rest; p=0.0002). Z 0 did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10 -6 ). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C PA reduction at maximum exercise. In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z 0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology.

PubMed

Chistiakov, Dimitry A; Grechko, Andrey V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Orekhov, Alexander N

2017-08-01

Cardiac obesity makes an important contribution to the pathogenesis of cardiovascular disease. One of the important pathways of this contribution is the inflammatory process that takes place in the adipose tissue. In this review, we consider the role of the cardiovascular system-associated fat in atherosclerotic cardiovascular pathology and a non-atherosclerotic cause of coronary artery disease, such as atrial fibrillation. Cardiovascular system-associated fat not only serves as the energy store, but also releases adipokines that control local and systemic metabolism, heart/vascular function and vessel tone, and a number of vasodilating and anti-inflammatory substances. Adipokine appears to play an important protective role in cardiovascular system. Under chronic inflammation conditions, the repertoire of signaling molecules secreted by cardiac fat can be altered, leading to a higher amount of pro-inflammatory messengers, vasoconstrictors, profibrotic modulators. This further aggravates cardiovascular inflammation and leads to hypertension, induction of the pathological tissue remodeling and cardiac fibrosis. Contemporary imaging techniques showed that epicardial fat thickness correlates with the visceral fat mass, which is an established risk factor and predictor of cardiovascular disease in obese subjects. However, this correlation is no longer present after adjustment for other covariates. Nevertheless, recent studies showed that pericardial fat volume and epicardial fat thickness can probably serve as a better indicator for atrial fibrillation. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive Plasma Metabolomic Analyses of Atherosclerotic Progression Reveal Alterations in Glycerophospholipid and Sphingolipid Metabolism in Apolipoprotein E-deficient Mice

PubMed Central

Dang, Vi T.; Huang, Aric; Zhong, Lexy H.; Shi, Yuanyuan; Werstuck, Geoff H.

2016-01-01

Atherosclerosis is the major underlying cause of most cardiovascular diseases. Despite recent advances, the molecular mechanisms underlying the pathophysiology of atherogenesis are not clear. In this study, comprehensive plasma metabolomics were used to investigate early-stage atherosclerotic development and progression in chow-fed apolipoprotein E-deficient mice at 5, 10 and 15 weeks of age. Comprehensive plasma metabolomic profiles, based on 4365 detected metabolite features, differentiate atherosclerosis-prone from atherosclerosis-resistant models. Metabolites in the sphingomyelin pathway were significantly altered prior to detectable lesion formation and at all subsequent time-points. The cytidine diphosphate-diacylglycerol pathway was up-regulated during stage I of atherosclerosis, while metabolites in the phosphatidylethanolamine and glycosphingolipid pathways were augmented in mice with stage II lesions. These pathways, involving glycerophospholipid and sphingolipid metabolism, were also significantly affected during the course of atherosclerotic progression. Our findings suggest that distinct plasma metabolomic profiles can differentiate the different stages of atherosclerotic progression. This study reveals that alteration of specific, previously unreported pathways of glycerophospholipid and sphingolipid metabolism are associated with atherosclerosis. The clear difference in the level of several metabolites supports the use of plasma lipid profiling as a diagnostic tool of atherogenesis. PMID:27721472

In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice.

PubMed

Yasuda, Satoshi; Ikuta, Kenjiro; Uwatoku, Toyokazu; Oi, Keiji; Abe, Kohtaro; Hyodo, Fuminori; Yoshimitsu, Kengo; Sugimura, Kohtaro; Utsumi, Hideo; Katayama, Yoshiki; Shimokawa, Hiroaki

2008-01-01

Magnetic resonance imaging (MRI) contrast agents that specifically detect atherosclerotic plaque may be useful for the noninvasive detection of the plaque. We have recently developed a new contrast agent, Evans blue-DTPA-gadolinium (EB-DTPA-Gd), which selectively accumulates vascular lesions with endothelial removal. In this study, we examined whether EB-DTPA-Gd is also useful for in vivo imaging of atherosclerotic plaques. We used male apolipoprotein-E-deficient (ApoE-/-) mice of different ages (3, 6 and 12 months old) and age-matched male wild-type mice. After a single intravenous administration of EB-DTPA-Gd (160 microM/kg body weight), MRI T(1) signal was obtained in vivo. Increased signal intensity in the aortic wall was noted within 10-20 min after intravenous injection of EB-DTPA-Gd and was maintained for 30 min. The MRI enhancement in the aorta of ApoE-/- mice was increased in accordance with age, whereas no such enhancement was noted in wild-type mice. Histological examination demonstrated that there was a topological correlation between the site of MRI enhancement and that of atherosclerotic plaque. These results indicate that EB-DTPA-Gd is a useful MRI contrast medium for the in vivo detection of atherosclerotic plaques. Copyright (c) 2007 S. Karger AG, Basel.

Detection of high-risk atherosclerotic lesions by time-resolved fluorescence spectroscopy based on the Laguerre deconvolution technique

NASA Astrophysics Data System (ADS)

Jo, J. A.; Fang, Q.; Papaioannou, T.; Qiao, J. H.; Fishbein, M. C.; Beseth, B.; Dorafshar, A. H.; Reil, T.; Baker, D.; Freischlag, J.; Marcu, L.

2006-02-01

This study introduces new methods of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data analysis for tissue characterization. These analytical methods were applied for the detection of atherosclerotic vulnerable plaques. Upon pulsed nitrogen laser (337 nm, 1 ns) excitation, TR-LIFS measurements were obtained from carotid atherosclerotic plaque specimens (57 endarteroctomy patients) at 492 distinct areas. The emission was both spectrally- (360-600 nm range at 5 nm interval) and temporally- (0.3 ns resolution) resolved using a prototype clinically compatible fiber-optic catheter TR-LIFS apparatus. The TR-LIFS measurements were subsequently analyzed using a standard multiexponential deconvolution and a recently introduced Laguerre deconvolution technique. Based on their histopathology, the lesions were classified as early (thin intima), fibrotic (collagen-rich intima), and high-risk (thin cap over necrotic core and/or inflamed intima). Stepwise linear discriminant analysis (SLDA) was applied for lesion classification. Normalized spectral intensity values and Laguerre expansion coefficients (LEC) at discrete emission wavelengths (390, 450, 500 and 550 nm) were used as features for classification. The Laguerre based SLDA classifier provided discrimination of high-risk lesions with high sensitivity (SE>81%) and specificity (SP>95%). Based on these findings, we believe that TR-LIFS information derived from the Laguerre expansion coefficients can provide a valuable additional dimension for the diagnosis of high-risk vulnerable atherosclerotic plaques.

Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet.

PubMed

Wang, Qiming; Zhang, Jian; Li, Yafei; Shi, Haojie; Wang, Hao; Chen, Bingrui; Wang, Fang; Wang, Zemu; Yang, Zhijian; Wang, Liansheng

2018-06-04

Epigallocatechin-3-gallate (EGCG), which is the principal component of green tea, has been shown to prevent the formation of atherosclerosis. However, the effect of EGCG on atherosclerotic plaque stability remains unknown. This study aimed to assess whether EGCG can enhance atherosclerotic plaque stability and to investigate the underlying mechanisms. Apolipoprotein E-deficient mice fed a high-fat diet were injected intraperitoneally with EGCG (10 mg/kg ) for 16 weeks. Cross sections of the brachiocephalic arteries were stained with hematoxylin and eosin (HE) for morphometric analyses or Masson's trichrome for collagen content analyses. Immunohistochemistry was performed to evaluate the percentage of macrophages and smooth muscle cells (SMCs). Protein expression and matrix metalloproteinase (MMP) activity were assayed by Western blot and gelatin zymography, respectively. Serum inflammatory cytokine levels were quantified by enzyme-linked immunosorbent assay. After 16 weeks of feeding the high-fat diet, there was clear atherosclerosis formation in the proximal brachiocephalic artery segments according to HE staining. EGCG treatment significantly increased the thickness of the fibrous cap. In the atherosclerotic plaques of the EGCG group, the relative macrophage content was decreased, whereas the relative SMC and collagen contents were increased. The expression levels of MMP-2, MMP-9 and extracellular matrix metalloproteinase inducer (EMMPRIN) were significantly decreased by EGCG treatment. In addition, EGCG treatment decreased the circulating TNF-a, IL-6, MCP-1 and IFN-γ levels in apolipoprotein E-deficient mice. EGCG promotes atherosclerotic lesion stability in apolipoprotein E-deficient mice. Potentially, these effects are mediated through the inhibition of inflammatory cytokine, MMPs and EMMPRIN expression.

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

PubMed Central

Wang, Tianyi; Jacob Mancuso, J.; Sapozhnikova, Veronika; Dwelle, Jordan; Ma, Li L.; Willsey, Brian; Shams Kazmi, S. M.; Qiu, Jinze; Li, Xiankai; Asmis, Reto; Johnston, Keith P.; Feldman, Marc D.

2012-01-01

Abstract. The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. PMID:22502567

Acute effects of Finnish sauna and cold-water immersion on haemodynamic variables and autonomic nervous system activity in patients with heart failure.

PubMed

Radtke, Thomas; Poerschke, Daniel; Wilhelm, Matthias; Trachsel, Lukas D; Tschanz, Hansueli; Matter, Friederike; Jauslin, Daniel; Saner, Hugo; Schmid, Jean-Paul

2016-04-01

The haemodynamic response to Finnish sauna and subsequent cold-water immersion in heart failure patients is unknown. Haemodynamic response to two consecutive Finnish sauna (80℃) exposures, followed by a final head-out cold-water immersion (12℃) was measured in 37 male participants: chronic heart failure (n = 12, 61.8 ± 9.2 years), coronary artery disease (n = 13, 61.2 ± 10.6 years) and control subjects (n = 12, 60.9 ± 8.9 years). Cardiac output was measured non-invasively with an inert gas rebreathing method prior to and immediately after the first sauna exposure and after cold-water immersion, respectively. Blood pressure was measured before, twice during and after sauna. The autonomic nervous system was assessed by power spectral analysis of heart rate variability. Total power, low-frequency and high-frequency components were evaluated. The low frequency/high frequency ratio was used as a marker of sympathovagal balance. Sauna and cold-water immersion were well tolerated by all subjects. Cardiac output and heart rate significantly increased in all groups after sauna and cold-water immersion (p < 0.05), except for coronary artery disease patients after sauna exposure. Systolic blood pressure during sauna decreased significantly in all groups with a nadir after 6 min (all p < 0.05). Cold-water immersion significantly increased systolic blood pressure in all groups (p < 0.05). No change in the low/high frequency ratio was found in chronic heart failure patients. In coronary artery disease patients and controls a prolonged increase in low frequency/high frequency ratio was observed after the first sauna exposure. Acute exposure to Finnish sauna and cold-water immersion causes haemodynamic alterations in chronic heart failure patients similarly to control subjects and in particular did not provoke an excessive increase in adrenergic activity or complex arrhythmias. © The European Society of Cardiology 2015.

Tissue oxygenation and haemodynamics measurement with spatially resolved NIRS

NASA Astrophysics Data System (ADS)

Zhang, Y.; Scopesi, F.; Serra, G.; Sun, J. W.; Rolfe, P.

2010-08-01

We describe the use of Near Infrared Spectroscopy (NIRS) for the non-invasive investigation of changes in haemodynamics and oxygenation of human peripheral tissues. The goal was to measure spatial variations of tissue NIRS oxygenation variables, namely deoxy-haemoglobin (HHb), oxy-haemoglobin (HbO2), total haemoglobin (HbT), and thereby to evaluate the responses of the peripheral circulation to imposed physiological challenges. We present a skinfat- muscle heterogeneous tissue model with varying fat thickness up to 15mm and a Monte Carlo simulation of photon transport within this model. The mean partial path length and the mean photon visit depth in the muscle layer were derived for different source-detector spacing. We constructed NIRS instrumentation comprising of light-emitting diodes (LED) as light sources at four wavelengths, 735nm, 760nm, 810nm and 850nm and sensitive photodiodes (PD) as the detectors. Source-detector spacing was varied to perform measurements at different depths within forearm tissue. Changes in chromophore concentration in response to venous and arterial occlusion were calculated using the modified Lambert-Beer Law. Studies in fat and thin volunteers indicated greater sensitivity in the thinner subjects for the tissue oxygenation measurement in the muscle layer. These results were consistent with those found using Monte Carlo simulation. Overall, the results of this investigation demonstrate the usefulness of the NIRS instrument for deriving spatial information from biological tissues.

Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system.

PubMed

Li, Xiang; Heber, Daniel; Rausch, Ivo; Beitzke, Dietrich; Mayerhoefer, Marius E; Rasul, Sazan; Kreissl, Michael; Mitthauser, Markus; Wadsak, Wolfgang; Hartenbach, Markus; Haug, Alexander; Zhang, Xiaoli; Loewe, Christian; Beyer, Thomas; Hacker, Marcus

2016-07-01

PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. SUVmax and TBRmax values are widely accepted reference

How does juxtaluminal calcium affect critical mechanical conditions in carotid atherosclerotic plaque? An exploratory study.

PubMed

Zhongzhao Teng; Jing He; Sadat, Umar; Mercer, John R; Xiaoyan Wang; Bahaei, Nasim S; Thomas, Owen M; Gillard, Jonathan H

2014-01-01

The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface, i.e., juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on computed tomography and magnetic resonance images and 3-D fluid-structure interaction simulation was used for mechanical analysis. The presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2-mm-thick fibrous cap (107.87 kPa [76.99, 129.14] versus 63.17 kPa [34.55, 75.13]; Median, [interquartile range]; ). Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p = 0.03). The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.

Enzyme-Sensitive MR Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques

PubMed Central

Ronald, John A.; Chen, John W.; Chen, Yuanxin; Hamilton, Amanda M.; Rodriguez, Elisenda; Reynolds, Fred; Hegele, Robert A.; Rogers, Kem A.; Querol, Manel; Bogdanov, Alexei; Weissleder, Ralph; Rutt, Brian K.

2009-01-01

Background Inflammation undermines the stability of atherosclerotic plaques, rendering them susceptible to acute rupture, the cataclysmic event that underlies clinical expression of this disease. Myeloperoxidase (MPO) is a central inflammatory enzyme secreted by activated macrophages, and is involved in multiple stages of plaque destabilization and patient outcome. We report here that a unique functional in vivo magnetic resonance (MR) agent can visualize MPO activity in atherosclerotic plaques in a rabbit model. Methods and Results We performed MR imaging of the thoracic aorta of New Zealand white (NZW) rabbits fed a cholesterol (n=11) or normal (n=4) diet up to 2 hours after injection of the MPO sensor bis-5HT-DTPA(Gd) (MPO(Gd)), the conventional agent, DTPA(Gd), or an MPO (Gd) analog, bis-tyr-DTPA(Gd), as controls. Delayed MPO(Gd) images (2 hour post injection) showed focal areas of increased contrast (>2-fold) in diseased wall, but not in normal wall (p=0.84), compared to both DTPA(Gd) (n=11; p<0.001) and bis-tyr-DTPA(Gd) (n=3; p<0.05). Biochemical assays confirmed that diseased wall possessed three-fold elevated MPO activity compared to normal wall (p<0.01). Areas detected by MPO(Gd) imaging co-localized and correlated with MPO-rich areas infiltrated by macrophages on histopathological evaluations (r=0.91, p<0.0001). While macrophages were the main source of MPO, not all macrophages secreted MPO, suggesting that distinct subpopulations contribute differently to atherogenesis and supporting our functional approach. Conclusions Our study represents a unique approach in the detection of inflammation in atherosclerotic plaques by examining macrophage function and the activity of an effector enzyme, to noninvasively provide both anatomic and functional information in vivo. PMID:19652086

Influence of ghrelin gene polymorphisms on hypertension and atherosclerotic disease.

PubMed

Berthold, Heiner K; Giannakidou, Eleni; Krone, Wilhelm; Trégouët, David-Alexandre; Gouni-Berthold, Ioanna

2010-02-01

Ghrelin is involved in several metabolic and cardiovascular processes. Recent evidence suggests its involvement in blood pressure regulation and hypertension. The aim of the study was to determine associations of single-nucleotide polymorphisms (SNPs) and haplotypes of the ghrelin gene (GHRL) with hypertension and atherosclerotic disease. Six GHRL SNPs (rs27647, rs26802, rs34911341, rs696217, rs4684677 and a -473G/A (with no assigned rsID)) were investigated in a sample of 1143 hypertensive subjects and 1489 controls of Caucasian origin. Both single-locus and haplotype association analyses were performed. In single-locus analyses, only the non-synonymous rs34911341 was associated with hypertension (odds ratio (OR)=1.95 (95% confidence interval (CI): 1.26-3.02), P=0.003). Six common haplotypes with frequency >1% were inferred from the studied GHRL SNPs, and their frequency distribution was significantly different between hypertensive subjects and controls (chi(2)=12.96 with 5 d.f. (degree of freedom), P=0.024). The effect of rs26802 was found to be significantly (P=0.017) modulated by other GHRL SNPs, as its C allele conferred either an increased risk (OR=1.30 (1.08-1.57), P=0.005) or a decreased risk (OR=0.50 (0.23-1.06), P=0.07) of hypertension according to the two different haplotypes on which it can be found. No association of GHRL SNPs or haplotypes with atherosclerotic disease was observed. In conclusion, we observed statistical evidence for association between GHRL SNPs and risk of hypertension.

Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in patients with intracranial atherosclerotic stenosis.

PubMed

Park, J-H; Hong, K-S; Lee, J; Kim, Y-J; Song, P

2013-04-01

Pre-existing brain infarct (PBI), frequently seen on magnetic resonance imaging and usually silent, is recognized as a risk factor for future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a risk predictor of ischaemic stroke and is associated with intracranial atherosclerotic stenosis (ICAS). However, little is known about the association of apoB/apoAI ratio with PBI. A total of 522 statin-/fibrate-naïve Korean patients, who experienced acute ischaemic stroke, were categorized into three groups: ICAS (n=254), extracranial (n=51), and no cerebral atherosclerotic stenosis (n=217). We explored the association between apoB/apoAI ratio and PBI lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location (deep subcortical [ds-PBI] versus hemispheric [h-PBI]), and symptomatic PBI (s-PBI) which was relevant to a prior clinical stroke event. Pre-existing brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(-) patients (0.81 ± 0.28 vs. 0.72 ± 0.23, P<0.001). In ICAS group, patients with higher apoB/apoAI ratio quartiles had more PBIs, ds-PBIs, and s-PBIs (P=0.020, P=0.025, and P=0.001, respectively). With multivariable analyses, the highest apoB/apoAI ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39-4.73), ds-PBI (2.48; 1.33-4.62), and advanced (≥ 3) ds-PBIs (2.68; 1.27-5.63) in ICAS group, but not with h-PBI. s-PBI had a dose-response relationship with apoB/apoAI ratio quartiles (6.18; 1.31-29.13 for the second; 5.34; 1.06-26.83 for the third; and 12.17; 2.50-59.19 for the fourth quartile), when referenced to the first quartile. ApoB/apoAI ratio is associated with asymptomatic deep subcortical ischaemic burden as well as with symptomatic lesion in patients with ICAS. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

PubMed

Dipla, Konstantina; Kousoula, Dimitra; Zafeiridis, Andreas; Karatrantou, Konstantina; Nikolaidis, Michalis G; Kyparos, Antonios; Gerodimos, Vassilis; Vrabas, Ioannis S

2016-06-01

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25 Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P < 0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women

Effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma.

PubMed

Wang, Lian-Dong; Gao, Xia; Li, Jun-Ying; Yu, Hong-Yan; Su, Hai-Wen; Liu, Lian-Zhong; Qi, Jun

2015-01-01

To investigate the effects of preemptive analgesia with parecoxib sodium on haemodynamics and plasma stress hormones in surgical patients with thyroid carcinoma. Fifty-seven patients with thyroid carcinoma who underwent thyroidectomy selectively in Laiwu Hospital Affiliated to Taishan Medical University and Binzhou People's Hospital were selected and randomly divided into three groups, 19 cases in each group. The control group was intravenously injected 0.9% sodium chloride injection before anesthesia induction; trial group I was intravenously injected with parecoxib sodium 20 min before anesthesia induction; based on trial group I, trial group II was injected with parecoxib sodium again 12 h after surgery. The levels of plasma norepinephrine (NE), cortisol (Cor) and blood glucose before, 12 and 24 h after surgery and changes of haemodynamics before surgery, at the end of surgery and 12, 24 and 48 h after surgery were compared in the three groups. Besides, visual analogue scale (VAS) scores were recorded 4, 8, 12 and 24 h after surgery. 12 and 24 h after surgery, the levels of plasma NE and Cor in three groups rose dramatically (P<0.05 or (P<0.01); The levels of plasma NE and Cor in trial groups I and II were evidently lower than in control group (P<0.05 or P<0.01), and those in trial group II slightly lower than in trial group I. 12 h after surgery, the heart rates (HR) and systolic pressures (SBP) in trial groups I and II increased obviously by comparison to surgery before (P<0.05 or P<0.01), but gradually returned to the preoperative level. HR, SBP and diastolic pressures (DBP) in trial groups I and II at the end of surgery and 12 h after surgery were all lower than in the control group, and significant differences were present (P<0.05 or (P<0.01). At 4, 8, 12 and 24 h after surgery, VAS scores in trial groups I and II were markedly lower than in the control group ((P<0.05 or (P<0.01), the scores in trial group II being the lowest. Combined application of

Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Gupta, Ajay; Baradaran, Hediyeh; Al-Dasuqi, Khalid; Knight-Greenfield, Ashley; Giambrone, Ashley E; Delgado, Diana; Wright, Drew; Teng, Zhongzhao; Min, James K; Navi, Babak B; Iadecola, Costantino; Kamel, Hooman

2016-08-15

Gadolinium enhancement on high-resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta-analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random-effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI-detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between-study heterogeneity using the Cochrane Q test and publication bias using the Begg-Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1-28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. Intracranial plaque enhancement on high-resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

PubMed

Leung, Thomas W; Wang, Lily; Soo, Yannie O Y; Ip, Vincent H L; Chan, Anne Y Y; Au, Lisa W C; Fan, Florence S Y; Lau, Alex Y L; Leung, Howan; Abrigo, Jill; Wong, Adrian; Mok, Vincent C T; Ng, Ping Wing; Tsoi, Tak Hong; Li, Siu Hung; Man, Celeste B L; Fong, Wing Chi; Wong, Ka Sing; Yu, Simon C H

2015-03-01

Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence. © 2014 American Neurological Association.

Apollo stent for symptomatic atherosclerotic intracranial stenosis: study results.

PubMed

Jiang, W-J; Xu, X-T; Jin, M; Du, B; Dong, K-H; Dai, J-P

2007-05-01

A recent trial shows an 8.3 per 100-patient-years' ischemic stroke rate in the territory of the intracranial stenotic artery, despite aspirin treatment. Our aim was to prospectively study the feasibility and outcome of a new intracranial balloon-expandable Apollo stent for symptomatic atherosclerotic intracranial stenosis (SAIS). Forty-six patients (41 men and 5 women; median, 54 years of age) with forty-eight >or=50% SAISs were enrolled. Procedural feasibility was evaluated by stent success (residual stenosis or=24 months), which varied from 1 month to 30.7 months (median, 23.9 months). After 30 days, 1 patient (2.2%, 1/46) developed minor stroke in the target-lesion artery territory at 6.7 months. Primary end point rate was 4.3 per 100 patient years. Angiographic follow-up was performed in 25 patients. Seven restenoses (28%, 7/25) were detected, 1 of which was symptomatic. Angioplasty with the Apollo stent for symptomatic atherosclerotic intracranial stenosis is feasible. Severe tortuosity is an independent predictor of stent failure. Our clinical outcome seems to compare favorably with results of aspirin therapy, but the restenotic rate was high.

A uni-extension study on the ultimate material strength and extreme extensibility of atherosclerotic tissue in human carotid plaques.

PubMed

Teng, Zhongzhao; Feng, Jiaxuan; Zhang, Yongxue; Sutcliffe, Michael P F; Huang, Yuan; Brown, Adam J; Jing, Zaiping; Lu, Qingsheng; Gillard, Jonathan H

2015-11-05

Atherosclerotic plaque rupture occurs when mechanical loading exceeds its material strength. Mechanical analysis has been shown to be complementary to the morphology and composition for assessing vulnerability. However, strength and stretch thresholds for mechanics-based assessment are currently lacking. This study aims to quantify the ultimate material strength and extreme extensibility of atherosclerotic components from human carotid plaques. Tissue strips of fibrous cap, media, lipid core and intraplaque hemorrhage/thrombus were obtained from 21 carotid endarterectomy samples of symptomatic patients. Uni-extension test with tissue strips was performed until they broke or slid. The Cauchy stress and stretch ratio at the peak loading of strips broken about 2mm away from the clamp were used to characterize their ultimate strength and extensibility. Results obtained indicated that ultimate strength of fibrous cap and media were 158.3 [72.1, 259.3] kPa (Median [Inter quartile range]) and 247.6 [169.0, 419.9] kPa, respectively; those of lipid and intraplaque hemorrhage/thrombus were 68.8 [48.5, 86.6] kPa and 83.0 [52.1, 124.9] kPa, respectively. The extensibility of each tissue type were: fibrous cap - 1.18 [1.10, 1.27]; media - 1.21 [1.17, 1.32]; lipid - 1.25 [1.11, 1.30] and intraplaque hemorrhage/thrombus - 1.20 [1.17, 1.44]. Overall, the strength of fibrous cap and media were comparable and so were lipid and intraplaque hemorrhage/thrombus. Both fibrous cap and media were significantly stronger than either lipid or intraplaque hemorrhage/thrombus. All atherosclerotic components had similar extensibility. Moreover, fibrous cap strength in the proximal region (closer to the heart) was lower than that of the distal. These results are helpful in understanding the material behavior of atherosclerotic plaques. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of atherosclerotic luminal narrowing of coronary arteries based on morphometrically generated visual guides.

PubMed

Barth, Rolf F; Kellough, David A; Allenby, Patricia; Blower, Luke E; Hammond, Scott H; Allenby, Greg M; Buja, L Maximilian

Determination of the degree of stenosis of atherosclerotic coronary arteries is an important part of postmortem examination of the heart, but, unfortunately, estimation of the degree of luminal narrowing can be imprecise and tends to be approximations. Visual guides can be useful to assess this, but earlier attempts to develop such guides did not employ digital technology. Using this approach, we have developed two computer-generated morphometric guides to estimate the degree of luminal narrowing of atherosclerotic coronary arteries. The first is based on symmetric or eccentric circular or crescentic narrowing of the vessel lumen and the second on either slit-like or irregularly shaped narrowing of the vessel lumens. Using the Aperio ScanScope XT at a magnification of 20× we created digital whole-slide images of 20 representative microscopic cross sections of the left anterior descending (LAD) coronary artery, stained with either hematoxylin and eosin (H&E) or Movat's pentachrome stain. These cross sections illustrated a variety of luminal profiles and degrees of stenosis. Three representative types of images were selected and a visual guide was constructed with Adobe Photoshop CS5. Using the "Scale" and "Measurement" tools, we created a series of representations of stenosis with luminal cross sections depicting 20%, 40%, 60%, 70%, 80%, and 90% occlusion of the LAD branch. Four pathologists independently reviewed and scored the degree of atherosclerotic luminal narrowing based on our visual guides. In addition, digital technology was employed to determine the degree of narrowing by measuring the cross-sectional area of the 20 microscopic sections of the vessels, first assuming no narrowing and then comparing this to the percent of narrowing determined by precise measurement. Two of the observers were very experienced general autopsy pathologists, one was a first-year pathology resident on his first rotation on the autopsy service, and the fourth observer was a

Intracerebral Hemorrhage Caused by Cerebral Hyperperfusion after Superficial Temporal Artery to Middle Cerebral Artery Bypass for Atherosclerotic Occlusive Cerebrovascular Disease

PubMed Central

Matano, Fumihiro; Murai, Yasuo; Mizunari, Takayuki; Adachi, Koji; Kobayashi, Shiro; Morita, Akio

Few papers have reported detailed accounts of intracerebral hemorrhage caused by cerebral hyperperfusion after superficial temporal artery to middle cerebral artery bypass (STA-MCA) bypass for atherosclerotic occlusive cerebrovascular disease. We report a case of vasogenic edema and subsequent intracerebral hemorrhage caused by the cerebral hyperperfusion syndrome (CHS) after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease disease without intense postoperative blood pressure control. A 63-year-old man with repeating left hemiparesis underwent magnetic resonance angiography (MRA), which revealed right internal carotid artery (ICA) occlusion. We performed a double bypass superficial temporal artery (STA)–middle cerebral artery (MCA) bypass surgery for the M2 and M3 branches. While the patient’s postoperative course was relatively uneventful, he suffered generalized convulsions, and computed tomography revealed a low area in the right frontal lobe on Day 4 after surgery. We considered this lesion to be pure vasogenic edema caused by cerebral hyperperfusion after revascularization. Intravenous drip infusion of a free radical scavenger (edaravone) and efforts to reduce systolic blood pressure to <120 mmHg were continued. The patient experienced severe left hemiparesis and disturbance of consciousness on Day 8 after surgery, due to intracerebral hemorrhage in the right frontal lobe at the site of the earlier vasogenic edema. Brain edema associated with cerebral hyperperfusion after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease should be recognized as a risk factor for intracerebral hemorrhage. The development of brain edema associated with CHS after STA-MCA bypass for atherosclerotic occlusive cerebrovascular disease requires not only intensive control of blood pressure, but also consideration of sedation therapy with propofol. PMID:28664022

Association of haemodynamic changes measured by serial central venous saturation during ultrafiltration for acutely decompensated heart failure with diuretic resistance and change in renal function.

PubMed

Vazir, Ali; Simpkin, Victoria L; Marino, Philip; Ludman, Andrew; Banya, Winston; Tavazzi, Guido; Bastin, Anthony J; Trenfield, Sarah; Ghori, Arshad; Alexander, Peter D; Griffiths, Mark; Price, Susanna; Sharma, Rakesh; Cowie, Martin R

2016-10-01

Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Δcreatinine) and whether Δcreatinine post UF is associated with mortality. Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Δcreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164±58 vs. 185±69μmol/l, P<0.01). ΔCVO2 was significantly associated with Δcreatinine [β-coefficient of -1.3 95%CI (-1.8 to -0.7), P<0.001] and remained significantly associated with Δcreatinine after considering changes in SBP, HR and PCV [P<0.001]. Ten (59%) patients died at 1-year and 15(88%) by 2-years. Δcreatinine was independently associated with mortality (adjusted-hazard ratio 1.03 (1.01 to 1.07) per 1μmol/l increase in creatinine; P=0.02). Haemodynamic changes during UF as measured by the surrogate of cardiac output was associated with Δcreatinine. Worsening renal function at end of UF treatment occurred in the majority of patients and was associated with mortality. Copyright © 2016. Published by Elsevier Ireland Ltd.

Haemodynamic results of replacement of mitral and aortic valves with autologous fascia lata prostheses

PubMed Central

Talavlikar, P. H.; Walbaum, P. R.; Kitchin, A. H.

1973-01-01

Twelve patients undergoing aortic and 28 undergoing mitral valve replacement with autologous fascia lata valves were studied before and six months after surgery. One aortic and 10 mitral valves were found to be significantly incompetent. Of the incompetent mitral valves, two appeared to have perivalvular leaks. Six of the remainder were associated with abnormal ventricular filling patterns. Valve failure was much less common when the design was modified to provide a loose cusp structure; out of 12 such valves none was incompetent. Transvalvular gradients persist with fascial valves though they are lower than with most mechanical prostheses. Ventricular function was greatly improved in successful aortic replacement but remained impaired in the case of mitral replacement. Valve failure appeared to be associated with, or accelerated by, haemodynamic stress rather than due to inevitable degenerative pathological processes. PMID:4731108

Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

PubMed

Zoccali, Carmine; Mallamaci, Francesca; Finocchiaro, Pietro

2002-11-01

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.

Selective ablation of rabbit atherosclerotic plaque with less thermal effect by the control of pulse structure of a quantum cascade laser in the 5.7 μm wavelength range

NASA Astrophysics Data System (ADS)

Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

2016-03-01

Cholesteryl esters are main components of atherosclerotic plaques and have an absorption peak at the wavelength of 5.75 μm originated from C=O stretching vibration mode of ester bond. Our group achieved the selective ablation of atherosclerotic lesions using a quantum cascade laser (QCL) in the 5.7 μm wavelength range. QCLs are relatively new types of semiconductor lasers that can emit mid-infrared range. They are sufficiently compact and considered to be useful for clinical application. However, large thermal effects were observed because the QCL worked as quasicontinuous wave (CW) lasers due to its short pulse interval. Then we tried macro pulse irradiation (irradiation of pulses at intervals) of the QCL and achieved effective ablation with less-thermal effects than conventional quasi-CW irradiation. However, lesion selectivity might be changed by changing pulse structure. Therefore, in this study, irradiation effects of the macro pulse irradiation to rabbit atherosclerotic plaque and normal vessel were compared. The macro pulse width and the macro pulse interval were set to 0.5 and 12 ms, respectively, because the thermal relaxation time of rabbit normal and atherosclerotic aortas in the oscillation wavelength of the QCL was 0.5-12 ms. As a result, cutting difference was achieved between rabbit atherosclerotic and normal aortas by the macro pulse irradiation. Therefore, macro pulse irradiation of a QCL in the 5.7 μm wavelength range is effective for reducing thermal effects and selective ablation of the atherosclerotic plaque. QCLs have the potential of realizing less-invasive laser angioplasty.

Exercise performance, haemodynamics, and respiratory pattern do not identify heart failure patients who end exercise with dyspnoea from those with fatigue.

PubMed

Morosin, Marco; Farina, Stefania; Vignati, Carlo; Spadafora, Emanuele; Sciomer, Susanna; Salvioni, Elisabetta; Sinagra, Gianfranco; Agostoni, Piergiuseppe

2018-02-01

The two main symptoms referred by chronic heart failure (HF) patients as the causes of exercise termination during maximal cardiopulmonary exercise testing (CPET) are muscular fatigue and dyspnoea. So far, a physiological explanation why some HF patients end exercise because of dyspnoea and others because of fatigue is not available. We assessed whether patients referring dyspnoea or muscular fatigue may be distinguished by different ventilator or haemodynamic behaviours during exercise. We analysed exercise data of 170 consecutive HF patients with reduced left ventricular ejection fraction in stable clinical condition. All patients underwent maximal CPET and a second maximal CPET with measurement of cardiac output by inert gas rebreathing at peak exercise. Thirty-eight (age 65.0 ± 11.1 years) and 132 (65.1 ± 11.4 years) patients terminated CPET because of dyspnoea and fatigue, respectively. Haemodynamic and cardiorespiratory parameters were the same in fatigue and dyspnoea patients. VO 2 was 10.4 ± 3.2 and 10.5 ± 3.3 mL/min/kg at the anaerobic threshold and 15.5 ± 4.8 and 15.4 ± 4.3 at peak, in fatigue and dyspnoea patients, respectively. In fatigue and dyspnoea patients, peak heart rate was 110 ± 22 and 114 ± 22 beats/min, and VE/VCO 2 and VO 2 /work relationship slopes were 31.2 ± 6.8 and 30.6 ± 8.2 and 10.6 ± 4.2 and 11.4 ± 5.5 L/min/W, respectively. Peak cardiac output was 6.68 ± 2.51 and 6.21 ± 2.55 L/min (P = NS for all). In chronic HF patients in stable clinical condition, fatigue and dyspnoea as reasons of exercise termination do not highlight different ventilatory or haemodynamic patterns during effort. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Competing risk of atherosclerotic risk factors for arterial and venous thrombosis in a general population: the Tromso study.

PubMed

Brækkan, Sigrid K; Hald, Erin M; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom; Rosendaal, Frits R; Hansen, John-Bjarne

2012-02-01

To investigate and compare the impact of traditional atherosclerotic risk factors for the risk of arterial and venous thrombosis, taking into account competing risks. In 1994-1995, 26,185 subjects were screened in the Tromsø study. Information on traditional atherosclerotic risk factors was obtained by physical examination, blood samples, and questionnaires. Subjects were followed to the first incident event of myocardial infarction (MI) or venous thromboembolism (VTE), or December 31, 2005. During a median of 10.8 years of follow-up, there were 1279 cases of incident MI and 341 VTE events. Advancing age and high body mass index were both associated with MI and VTE. Hazard ratio per decade of age was 2.34 (95% CI: 2.25-2.43) for MI and 1.87 (1.74-2.01) for VTE, and 3 kg/m(2) increase in body mass index was associated with 1.16 (1.11-1.21) and 1.20 (1.12-1.29) increased risk of MI and VTE, respectively. Blood pressure, high levels of triglycerides and total cholesterol, low HDL cholesterol, self-reported diabetes, and smoking were all associated with increased risk of MI but not associated with VTE. Our findings imply that traditional atherosclerotic risk factors, such as smoking, hypertension, dyslipidemia, and diabetes mellitus are not shared by arterial and venous thrombosis.

Intravascular Raman spectroscopic catheter for molecular diagnosis of atherosclerotic coronary disease

NASA Astrophysics Data System (ADS)

Komachi, Yuichi; Sato, Hidetoshi; Tashiro, Hideo

2006-10-01

An intravascular catheter for Raman spectroscopic detection and analysis of coronary atherosclerotic disease has been developed. The catheter, having an outer diameter of 2 mm, consisted of a side-view-type micro-Raman probe, an imaging fiber bundle, a working channel (injection drain), and a balloon. By inflating the balloon, the probe was brought close to the inner wall of a modeled blood flow system and detected a phantom target buried in the wall. Results obtained demonstrate the possibility of using the spectroscopic catheter for molecular diagnosis of coronary lesions.

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study

PubMed Central

2014-01-01

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb

Dispersive aortic cannulas reduce aortic wall shear stress affecting atherosclerotic plaque embolization.

PubMed

Assmann, Alexander; Gül, Fethi; Benim, Ali Cemal; Joos, Franz; Akhyari, Payam; Lichtenberg, Artur

2015-03-01

Neurologic complications during on-pump cardiovascular surgery are often induced by mobilization of atherosclerotic plaques, which is directly related to enhanced wall shear stress. In the present study, we numerically evaluated the impact of dispersive aortic cannulas on aortic blood flow characteristics, with special regard to the resulting wall shear stress profiles. An idealized numerical model of the human aorta and its branches was created and used to model straight as well as bent dispersive aortic cannulas with meshlike tips inserted in the distal ascending aorta. Standard cannulas with straight beveled or bent tips served as controls. Using a recently optimized computing method, simulations of pulsatile and nonpulsatile extracorporeal circulation were performed. Dispersive aortic cannulas reduced the maximum and average aortic wall shear stress values to approximately 50% of those with control cannulas, while the difference in local values was even larger. Moreover, under pulsatile circulation, dispersive cannulas shortened the time period during which wall shear stress values were increased. The turbulent kinetic energy was also diminished by utilizing dispersive cannulas, reducing the risk of hemolysis. In summary, dispersive aortic cannulas decrease aortic wall shear stress and turbulence during extracorporeal circulation and may therefore reduce the risk of endothelial and blood cell damage as well as that of neurologic complications caused by atherosclerotic plaque mobilization. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Stable phase post-MI patients have elevated VEGF levels correlated with inflammation markers, but not with atherosclerotic burden.

PubMed

ErŽen, Barbara; Šilar, Mira; Šabovič, Mišo

2014-11-22

The role of vascular endothelial growth factor (VEGF) in patients in the stable phase after myocardial infarction (MI) has not yet been explored. Therefore, we compared the values of VEGF in post-MI patients with those obtained in healthy controls. Furthermore, we investigated whether the values of VEGF correlate to either inflammation markers or the atherosclerotic burden. 41 male patients (on average 44 years old) in the stable phase after MI (on average 20.5 months after MI) were recruited, while 25 healthy age-matched males served as controls. Plasma levels of VEGF and several markers of inflammation were measured by standard procedures. The atherosclerotic burden was determined by the angiographic severity of coronary atherosclerosis, endothelial dysfunction (measured by ultrasound measurement of the flow mediated dilation of the brachial artery), the intima-media thickness of the common carotid artery and the ankle-brachial pressure index. VEGF values were significantly elevated in post-MI patients compared to the controls (53.8 ± 42.7 pg/ml vs. 36.3 ± 8.9 pg/ml, p = 0.014). The elevated VEGF values significantly correlated to the (increased) values of the inflammatory molecules interleukin 6 and 8 (r = 0.37, p = 0.017; and r = 0.45, p = 0.003; respectively). In contrast, no correlation was found between VEGF and the parameters of the atherosclerotic burden, although FMD and IMT were significantly impaired in patients. We found that plasma levels of VEGF are increased in the stable phase after MI and correlate with inflammation cytokines, but not with the atherosclerotic burden. Thus, this suggests that increased levels of VEGF are a part of ongoing inflammatory activity. Since VEGF in these patients stimulates neovascularization of inflamed plaques and induces their destabilization, the VEGF level can have an important negative prognostic value. Clearly, further studies are needed to clarify the role of VEGF as a prognostic marker.

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

PubMed Central

Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

2017-01-01

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

PubMed

Hetterich, Holger; Webber, Nicole; Willner, Marian; Herzen, Julia; Birnbacher, Lorenz; Hipp, Alexander; Marschner, Mathias; Auweter, Sigrid D; Habbel, Christopher; Schüller, Ulrich; Bamberg, Fabian; Ertl-Wagner, Birgit; Pfeiffer, Franz; Saam, Tobias

2016-09-01

To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

Relative myotoxic and haemodynamic effects of the beta-agonists fenoterol and clenbuterol measured in conscious unrestrained rats.

PubMed

Burniston, Jatin G; Tan, Lip-Bun; Goldspink, David F

2006-11-01

The beta(2)-adrenoceptor (beta(2)-AR) agonists clenbuterol and fenoterol have similar beneficial effects in animal models of heart failure. However, large doses of clenbuterol can induce cardiomyocyte death, and it is not known which of these agents has the most favourable therapeutic profile. We have investigated the cardiotoxicity of clenbuterol and fenoterol alongside that of isoprenaline, and compared their haemodynamic effects. Wistar rats (n = 6 per group) were subcutaneously injected with each beta-agonist (0.003-3 mmol kg(-1)) or saline, and cardiomyocyte apoptosis was detected by caspase 3 immunohistochemistry. In a separate experiment, rats (n = 4) were given equivalent doses to those used in the myotoxicity studies, in a randomized cross-over design, and their blood pressure recorded via radiotelemetry. Injection of 0.3 mmol kg(-1) fenoterol or isoprenaline, but not clenbuterol, induced significant cardiomyocyte apoptosis (0.4 +/- 0.05%; P < 0.05). At 3 mmol kg(-1), all agonists induced apoptosis (fenoterol, 1.1 +/- 0.1%; isoprenaline, 0.9 +/- 0.8%; and clenbuterol, 0.4 +/- 0.07%; P < 0.05). beta(1)-Adrenoceptor antagonism (10 mg kg(-1) bisoprolol) prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by beta(2)-AR antagonism (10 mg kg(-1) ICI 118 551). Clenbuterol decreased diastolic (1.3- to 1.6-fold; P < 0.05) and systolic blood pressure (1.3-fold; P < 0.05), and doses > 0.3 mmol kg(-1) increased heart rate (1.4-fold; P < 0.05). Fenoterol increased heart rate (1.2- to 1.4-fold; P < 0.05), and doses > 0.3 mmol kg(-1) decreased diastolic blood pressure (1.3-fold; P < 0.05). In conclusion, the cardiotoxicity of fenoterol was similar to isoprenaline and greater than clenbuterol, and fenoterol had less desirable haemodynamic effects.

Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process.

PubMed

Chen, Lihua; Liu, Wenen; Li, Yanming; Luo, San; Liu, Qingxia; Zhong, Yiming; Jian, Zijuan; Bao, Meihua

2013-09-01

The aim of this study was to investigate the effect of Lactobacillus (L.) acidophilus ATCC 4356 on the progression of atherosclerosis in Apoliprotein-E knockout (ApoE(-/-)) mice and the underlying mechanisms. Eight week-old ApoE(-/-) mice were treated with L. acidophilus ATCC 4356 daily for 12 weeks. The wild type (WT) mice or ApoE(-/-) mice in the vehicle group were treated with saline only. Body weights, serum lipid levels, aortic atherosclerotic lesions, and tissue oxidative and inflammatory statuses were examined among the groups. As compared to ApoE(-/-) mice in the vehicle group, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 had no changes in body weights and serum lipid profiles, but showed decreased atherosclerotic lesion size in en face aorta. In comparison with WT mice, ApoE(-/-) mice in the vehicle group showed higher levels of serum malondialdehyde (MDA), oxidized low density lipoprotein (oxLDL) and tumor necrosis factor-alpha (TNF-α), but lower levels of interleukin-10 (IL-10) and superoxide dismutase (SOD) activities in serum. Administration of L. acidophilus ATCC 4356 could reverse these trends in a dose-dependent manner in ApoE(-/-) mice. Furthermore, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 showed an inhibition of translocation of NF-κB p65 from cytoplasm to nucleus, suppression of degradation of aortic IκB-α, and improvements of gut microbiota distribution, as compared to ApoE(-/-) mice in the vehicle group. Our findings suggest that administration of L. acidophilus ATCC 4356 can attenuate the development of atherosclerotic lesions in ApoE(-/-) mice through reducing oxidative stress and inflammatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

Propofol-fentanyl anaesthesia at high altitude: anaesthetic requirements and haemodynamic variations when compared with anaesthesia at low altitude.

PubMed

Puri, G D; Jayant, A; Dorje, M; Tashi, M

2008-03-01

There are few published accounts of anaesthesia delivery at high altitude. Natives at high altitude are known to have altered cardiorespiratory reserve. This study seeks to demonstrate the safety of propofol-fentanyl anaesthesia at high altitude titrated to the bispectral index (BIS) (3505 metres above sea level) in native highlanders. It also shows the differential effects of anaesthesia and surgery on the haemodynamics of such individuals as compared with individuals living at low altitude. Fifteen consenting adults scheduled to undergo general surgical/orthopaedic procedures under general anaesthesia using fentanyl, and propofol infusions titrated to the BIS along with nitrous oxide in oxygen after intubation, were recruited in the high-altitude arm. Their anaesthesia record was compared with retrospective data from low altitude with respect to anaesthetic requirements, recovery after anaesthesia and the haemodynamic responses to surgical stress. The high-altitude dwellers required significantly larger doses of propofol at anaesthetic induction (2.31+/-0.64 vs. 1.41+/-0.24 mg/kg, P<0.0001) and thereafter to maintain designated BIS than their low-altitude counterparts (6.22+/-1.14 vs. 4.61+/-1.29 mg/kg/h, P<0.01). They, however, had uneventful and short recovery times. The high-altitude population also had significantly lower baseline heart rates (72+/-9.83 vs. 88+/-12.1, P<0.04) as also the heart rate responses to noxious stimulation such as direct laryngoscopy or skin incision (P<0.04, P<0.005, respectively). High-altitude dwellers require significantly larger amounts of intravenous anaesthetic propofol. Heart rate at rest as also the heart rate responses to surgical stress were significantly attenuated at high altitude.

Dynamic muscle O2 saturation response is impaired during major non-cardiac surgery despite goal-directed haemodynamic therapy.

PubMed

Feldheiser, A; Hunsicker, O; Kaufner, L; Köhler, J; Sieglitz, H; Casans Francés, R; Wernecke, K-D; Sehouli, J; Spies, C

2016-03-01

Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown. This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2. At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion. Using near-infrared spectroscopy combined with a VOT during surgery showed a gradual deterioration of MVR in patients treated with optimal haemodynamic care. The deterioration of MVR was accompanied by the transition to a surgically induced systemic inflammatory response state. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Penetrating atherosclerotic ulcer at the proximal aorta complicated with cardiac tamponade and aortic valve regurgitation.

PubMed

Yano, K; Makino, N; Hirayama, H; Hatakenaka, M; Matsui, H; Soeda, T; Hadama, T

1999-03-01

A 56-year-old man had a penetrating atherosclerotic ulcer originating in the proximal ascending aorta, which is an unusual case of penetrating aortic ulcer complicated with the aortic valve regurgitation and cardiac tamponade. This hemodynamically unstable patient was successfully treated by conservative management to control his blood pressure and was also monitored closely with follow-up imaging studies.

Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques

PubMed Central

Majmudar, Maulik D.; Yoo, Jeongsoo; Keliher, Edmund J.; Truelove, Jessica; Iwamoto, Yoshiko; Sena, Brena; Dutta, Partha; Borodovsky, Anna; Fitzgerald, Kevin; Di Carli, Marcelo; Libby, Peter; Anderson, Daniel G.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

2013-01-01

Rationale Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocyte and macrophages (Mo/Mϕ) could serve as a biomarker of disease progression and therapeutic intervention. Objective To noninvasively assess plaque inflammation with dextran nanoparticle-facilitated hybrid PET/MR imaging. Methods and Results Using clinically approved building blocks, we systematically developed 13nm polymeric nanoparticles consisting of crosslinked short chain dextrans which were modified with desferoxamine for zirconium-89 radiolabeling (89Zr-DNP) and a near infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in Mo/Mϕ (76.7%) and lower signal originating from other leukocytes such as neutrophils and lymphocytes (11.8% and 0.7%, p<0.05 versus Mo/Mϕ). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of 89Zr-DNP in the aortic root of ApoE−/− mice (standard uptake value, ApoE−/− mice versus wild type controls, 1.9±0.28 versus 1.3±0.03, p<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor CCR2 with siRNA decreased 89Zr-DNP plaque signal (p<0.05) and inflammatory gene expression (p<0.05). Conclusions Hybrid PET/MR imaging with a 13nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy. PMID:23300273

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

PubMed

Merghani, Ahmed; Maestrini, Viviana; Rosmini, Stefania; Cox, Andrew T; Dhutia, Harshil; Bastiaenan, Rachel; David, Sarojini; Yeo, Tee Joo; Narain, Rajay; Malhotra, Aneil; Papadakis, Michael; Wilson, Mathew G; Tome, Maite; AlFakih, Khaled; Moon, James C; Sharma, Sanjay

2017-07-11

Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P =0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P =0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC

Classification of human coronary atherosclerotic plaques using ex vivo high-resolution multicontrast-weighted MRI compared with histopathology.

PubMed

Li, Tao; Li, Xin; Zhao, Xihai; Zhou, Weihua; Cai, Zulong; Yang, Li; Guo, Aitao; Zhao, Shaohong

2012-05-01

The objective of our study was to evaluate the feasibility of ex vivo high-resolution multicontrast-weighted MRI to accurately classify human coronary atherosclerotic plaques according to the American Heart Association classification. Thirteen human cadaver heart specimens were imaged using high-resolution multicontrast-weighted MR technique (T1-weighted, proton density-weighted, and T2-weighted). All MR images were matched with histopathologic sections according to the landmark of the bifurcation of the left main coronary artery. The sensitivity and specificity of MRI for the classification of plaques were determined, and Cohen's kappa analysis was applied to evaluate the agreement between MRI and histopathology in the classification of atherosclerotic plaques. One hundred eleven MR cross-sectional images obtained perpendicular to the long axis of the proximal left anterior descending artery were successfully matched with the histopathologic sections. For the classification of plaques, the sensitivity and specificity of MRI were as follows: type I-II (near normal), 60% and 100%; type III (focal lipid pool), 80% and 100%; type IV-V (lipid, necrosis, fibrosis), 96.2% and 88.2%; type VI (hemorrhage), 100% and 99.0%; type VII (calcification), 93% and 100%; and type VIII (fibrosis without lipid core), 100% and 99.1%, respectively. Isointensity, which indicates lipid composition on histopathology, was detected on MRI in 48.8% of calcified plaques. Agreement between MRI and histopathology for plaque classification was 0.86 (p < 0.001). Ex vivo high-resolution multicontrast-weighted MRI can accurately classify advanced atherosclerotic plaques in human coronary arteries.

Effect of intraplaque angiogenesis to atherosclerotic rupture-prone plaque induced by high shear stress in rabbit model

PubMed Central

Qiu, Juhui; Lei, Daoxi; Hu, Jianjun; Yin, Tieying; Zhang, Kang; Yu, Donghong

2017-01-01

Abstract Atherosclerotic prone-rupture plaque is mainly localized in the region of the entrance to the stenosis with high shear stress and the reasons are largely unknown. Our hypothesis is that such a distribution of cells in atherosclerotic plaque may depend on the angiogenesis. Silastic collars induced regions of high shear stress (20.68 ± 5.27 dynes/cm2) in the upstream flow and low shear stress (12.25 ± 1.28 dynes/cm2) in the downstream flow in carotid arteries. Compared with the low shear stress region, plaques in the high shear stress region showed more intraplaque haemorrhaging, less collagen and higher apoptotic rates of vascular smooth muscle cells; endothelial cells (ECs) in the high shear stress region were characterized with integrity and high endothelial nitric oxide synthase (eNOS) expression (1570.3 ± 345.5% vs 172.9 ± 49.9%). The number of intraplaque microvessels is very high in the high shear stress region (15 ± 1.8 n/mm2 vs 3.5 ± 0.4 n/mm2), and the microvessels in the plaque show ECs were abnormal, with membrane blebs, intracytoplasmic vacuoles and leukocyte infiltration. Our current study reveals that the integrity of the endothelium and the vulnerability of atherosclerotic plaques are simultaneously localized in high shear stress regions, and we provide evidence for the first time that microvessels in the intraplaque maybe responsible for rupture-prone plaque formation in the high shear stress region. PMID:28798867

Exposure to Cigarette Smoke and the Morphology of Atherosclerotic Plaques in the Extracranial Arteries Assessed by Computed Tomography Angiography in Patients with Essential Hypertension.

PubMed

Gać, Paweł; Jaźwiec, Przemysław; Mazur, Grzegorz; Poręba, Rafał

2017-01-01

The aim of the study was to determine the relationship between exposure to cigarette smoke and the morphology of atherosclerotic plaques in the extracranial arteries assessed by computed tomography angiography in patients with hypertension. The study included 61 hypertensive patients: 17 active smokers (group A), 18 non-smokers, declaring environmental exposure to tobacco smoke (group B), and 26 non-smokers, not declaring exposure to cigarette smoke (group C). The number of segments with plaques was significantly higher in group A compared to groups B and C. The number of segments with non-calcified and mixed plaques was significantly higher in group A and group B than in group C. A positive correlation between cigarette-years and the number of segments with atherosclerotic plaques was noted. In summary, both active smoking and environmental exposure to tobacco smoke appear to increase the number of segments of the extracranial arteries with non-calcified and mixed atherosclerotic plaques.

Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension.

PubMed

Chaouat, Ari; Sitbon, Olivier; Mercy, Magalie; Ponçot-Mongars, Raphaëlle; Provencher, Steeve; Guillaumot, Anne; Gomez, Emmanuel; Selton-Suty, Christine; Malvestio, Pascale; Regent, Denis; Paris, Christophe; Hervé, Philippe; Chabot, François

2014-09-01

The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. ©ERS 2014.

Material properties of components in human carotid atherosclerotic plaques: a uniaxial extension study.

PubMed

Teng, Zhongzhao; Zhang, Yongxue; Huang, Yuan; Feng, Jiaxuan; Yuan, Jianmin; Lu, Qingsheng; Sutcliffe, Michael P F; Brown, Adam J; Jing, Zaiping; Gillard, Jonathan H

2014-12-01

Computational modelling to calculate the mechanical loading within atherosclerotic plaques has been shown to be complementary to defining anatomical plaque features in determining plaque vulnerability. However, its application has been partially impeded by the lack of comprehensive knowledge about the mechanical properties of various tissues within the plaque. Twenty-one human carotid plaques were collected from endarterectomy. The plaque was cut into rings, and different type of atherosclerotic tissues, including media, fibrous cap (FC), lipid and intraplaque haemorrhage/thrombus (IPH/T) was dissected for uniaxial extension testing. In total, 65 media strips from 17 samples, 59 FC strips from 14 samples, 38 lipid strips from 11 samples, and 21 IPH/T strips from 11 samples were tested successfully. A modified Mooney-Rivlin strain energy density function was used to characterize the stretch-stress relationship. The stiffnesses of media and FC are comparable, as are lipid and IPH/T. However, both media and FC are stiffer than either lipid or IPH/T. The median values of incremental Young's modulus of media, FC, lipid and IPH/T at λ=1 are 290.1, 244.5, 104.4, 52.9, respectively; they increase to 1019.5, 817.4, 220.7 and 176.9 at λ=1.1; and 4302.7, 3335.0, 533.4 and 268.8 at λ=1.15 (unit, kPa; λ, stretch ratio). The material constants of each tissue type are suggested to be: media, c1=0.138kPa, D1=3.833kPa and D2=18.803; FC, c1=0.186kPa, D1=5.769kPa and D2=18.219; lipid, c1=0.046kPa, D1=4.885kPa and D2=5.426; and IPH/T, c1=0.212kPa, D1=4.260kPa and D2=5.312. It is concluded that all soft atherosclerotic tissues are non-linear, and both media and FC are stiffer than either lipid or IPH/T. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.

PubMed

Nie, Shufang; Zhang, Jia; Martinez-Zaguilan, Raul; Sennoune, Souad; Hossen, Md Nazir; Lichtenstein, Alice H; Cao, Jun; Meyerrose, Gary E; Paone, Ralph; Soontrapa, Suthipong; Fan, Zhaoyang; Wang, Shu

2015-12-28

Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

Venous haemodynamics of Jet Impulse Technology within a lower limb fibreglass cast: a randomized controlled trial

PubMed Central

Mackintosh, Stephen; Buchanan, Samantha; Schwarzenlander, Kerstin; De Ruyter, Bernadette

2017-01-01

Objectives We investigated popliteal venous haemodynamics of the VenaJet Jet Impulse Technology system within a below-knee fibreglass cast. Design Randomized controlled trial. Participants Twenty-four healthy participants aged 18–54 had both feet placed within the Jet Impulse Technology system and were randomised for one or other leg to be within a below-knee fibreglass cast. Setting Pacific Radiology, Lower Hutt, Wellington Main outcome measures The primary outcome variable was peak systolic velocity (cm/s) compared between legs with and without the cast at 60 min (after 10 min Jet Impulse Technology activation), using a mixed linear model and a non-inferiority bound of 4.8 cm/s. Secondary outcome variables were the difference in peak systolic velocity between the casted limb and the non-casted limb at baseline and 40 min after casting, and the difference in mean flow velocity (cm/s), vein diameter (mm), and total volume flow (L/min) between the casted limb and the non-casted limb at baseline, 40 and 60 min. Results The mean (standard deviation) peak systolic velocity was 4.6(1.5), 4.8(1.1), 28.8(16.1), and 4.3(1.2), 4.8(1.4) and 29.3(19.0) cm/s at baseline, 40 and 60 min in the casted and non-casted leg, respectively. The difference (95% confidence interval) between cast and no-cast at 60 min was −0.8 (−6.5 to 4.9) cm/s, P = 0.78. The peak systolic velocity, flow velocity and total volume flow at 40 min were not statistically significantly different from baseline for both casted and non-casted limb. Conclusion In healthy volunteers, the popliteal venous haemodynamics of the Jet Impulse Technology system was similar between the legs with and without a below-knee fibreglass cast. In-cast Jet Impulse Technology may provide a non-pharmacological option for venous thromboembolism prophylaxis for lower-limb cast-immobility. PMID:28203384

Venous haemodynamics of Jet Impulse Technology within a lower limb fibreglass cast: a randomized controlled trial.

PubMed

Braithwaite, Irene; Mackintosh, Stephen; Buchanan, Samantha; Schwarzenlander, Kerstin; De Ruyter, Bernadette

2017-02-01

We investigated popliteal venous haemodynamics of the VenaJet Jet Impulse Technology system within a below-knee fibreglass cast. Randomized controlled trial. Twenty-four healthy participants aged 18-54 had both feet placed within the Jet Impulse Technology system and were randomised for one or other leg to be within a below-knee fibreglass cast. Pacific Radiology, Lower Hutt, Wellington. The primary outcome variable was peak systolic velocity (cm/s) compared between legs with and without the cast at 60 min (after 10 min Jet Impulse Technology activation), using a mixed linear model and a non-inferiority bound of 4.8 cm/s. Secondary outcome variables were the difference in peak systolic velocity between the casted limb and the non-casted limb at baseline and 40 min after casting, and the difference in mean flow velocity (cm/s), vein diameter (mm), and total volume flow (L/min) between the casted limb and the non-casted limb at baseline, 40 and 60 min. The mean (standard deviation) peak systolic velocity was 4.6(1.5), 4.8(1.1), 28.8(16.1), and 4.3(1.2), 4.8(1.4) and 29.3(19.0) cm/s at baseline, 40 and 60 min in the casted and non-casted leg, respectively. The difference (95% confidence interval) between cast and no-cast at 60 min was -0.8 (-6.5 to 4.9) cm/s, P  = 0.78. The peak systolic velocity, flow velocity and total volume flow at 40 min were not statistically significantly different from baseline for both casted and non-casted limb. In healthy volunteers, the popliteal venous haemodynamics of the Jet Impulse Technology system was similar between the legs with and without a below-knee fibreglass cast. In-cast Jet Impulse Technology may provide a non-pharmacological option for venous thromboembolism prophylaxis for lower-limb cast-immobility.

The influence of computational assumptions on analysing abdominal aortic aneurysm haemodynamics.

PubMed

Ene, Florentina; Delassus, Patrick; Morris, Liam

2014-08-01

The variation in computational assumptions for analysing abdominal aortic aneurysm haemodynamics can influence the desired output results and computational cost. Such assumptions for abdominal aortic aneurysm modelling include static/transient pressures, steady/transient flows and rigid/compliant walls. Six computational methods and these various assumptions were simulated and compared within a realistic abdominal aortic aneurysm model with and without intraluminal thrombus. A full transient fluid-structure interaction was required to analyse the flow patterns within the compliant abdominal aortic aneurysms models. Rigid wall computational fluid dynamics overestimates the velocity magnitude by as much as 40%-65% and the wall shear stress by 30%-50%. These differences were attributed to the deforming walls which reduced the outlet volumetric flow rate for the transient fluid-structure interaction during the majority of the systolic phase. Static finite element analysis accurately approximates the deformations and von Mises stresses when compared with transient fluid-structure interaction. Simplifying the modelling complexity reduces the computational cost significantly. In conclusion, the deformation and von Mises stress can be approximately found by static finite element analysis, while for compliant models a full transient fluid-structure interaction analysis is required for acquiring the fluid flow phenomenon. © IMechE 2014.

Short-term effect of severe exposure to methylmercury on atherosclerotic heart disease and hypertension mortality in Minamata.

PubMed

Inoue, Sachiko; Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki

2012-02-15

Recent studies suggest potential adverse effects of methylmercury exposure on myocardial infarction and hypertension, although the evidence is still limited. We thus evaluated this association using age-standardized mortality ratios (ASMRs) in Minamata, where severe methylmercury poisoning had occurred. We obtained mortality data from annual vital statistics and demographic statistics from census. We then compared mortality of atherosclerotic heart disease including degenerative heart disease and hypertension in Minamata-city with those in Kumamoto Prefecture, which includes Minamata city, as a control. We estimated ASMRs and 95% confidence intervals (CIs) during the period from 1953 to 1970. ASMRs of atherosclerotic heart disease were continuously decreased during the period from 1953 to 1967. In contrast, the ASMR of hypertension was significantly elevated during the period from 1963 to 1967 (SMR=1.38, CI; 1.06-1.80); but they decreased later. Although dilution is present in this ecological study, our study supports the notion that methylmercury exposure induces hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

PubMed Central

Zhou, X; Paulsson, G; Stemme, S; Hansson, G K

1998-01-01

Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the

Patient-specific CFD simulation of intraventricular haemodynamics based on 3D ultrasound imaging.

PubMed

Bavo, A M; Pouch, A M; Degroote, J; Vierendeels, J; Gorman, J H; Gorman, R C; Segers, P

2016-09-09

The goal of this paper is to present a computational fluid dynamic (CFD) model with moving boundaries to study the intraventricular flows in a patient-specific framework. Starting from the segmentation of real-time transesophageal echocardiographic images, a CFD model including the complete left ventricle and the moving 3D mitral valve was realized. Their motion, known as a function of time from the segmented ultrasound images, was imposed as a boundary condition in an Arbitrary Lagrangian-Eulerian framework. The model allowed for a realistic description of the displacement of the structures of interest and for an effective analysis of the intraventricular flows throughout the cardiac cycle. The model provides detailed intraventricular flow features, and highlights the importance of the 3D valve apparatus for the vortex dynamics and apical flow. The proposed method could describe the haemodynamics of the left ventricle during the cardiac cycle. The methodology might therefore be of particular importance in patient treatment planning to assess the impact of mitral valve treatment on intraventricular flow dynamics.

Paraoxonase 1: a better atherosclerotic risk predictor than HDL in type 2 diabetes mellitus.

PubMed

Patra, Surajeet Kumar; Singh, Kamna; Singh, Ritu

2013-01-01

Type 2 diabetes mellitus is a state of glycative stress and oxidative stress. Lower level of serum PON 1 has been correlated to higher morbidity and mortality related to cardiovascular complications in type 2 diabetes mellitus. To estimate and compare the serum PON 1 levels in type 2 diabetes mellitus and controls and to predict which one is the better atherosclerotic risk predictor among HDL and PON 1 in T2DM patients. An observational analytical case-control study was conducted with a sample size of 30 in two groups like group I (30 cases of type 2 diabetes mellitus diagnosed by ADA 2010 criteria) and group II (30 age and sex matched controls). Human serum paroxonase 1 levels were measured by ELISA. Both HDL and PON 1 were negatively correlated with the various atherogenic indices (AIP, AC, CRI I, CRI II) but the strength of negative correlation is always greater for PON 1. In multiple linear regression analysis, we found that the regression coefficient (β) is always higher for PON 1 than for HDL while taking the atherogenic indices as outcome variable. PON 1 can be a better predictor than HDL for atherosclerotic risk in type 2 diabetes mellitus. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Combination of fluvastatin and losartan relieves atherosclerosis and macrophage infiltration in atherosclerotic plaques in rabbits

PubMed Central

Yang, Ya-pei; Dong, Qiu-li; Zhang, Xu-hong; Zhang, Yue-hui; Zhu, Li; Li, Shu-ying; Liu, Zhong-zhi; Xu, Hui; Wang, Nan; Jiang, Hong; Liu, Chun-xi; Liu, Xian-xi; Dong, Bo

2011-01-01

Aim: To investigate whether the combination of fluvastatin and losartan synergistically relieve atherosclerosis and plaque inflammation induced by a high-cholesterol diet in rabbits. Methods: Atherosclerosis was induced with a high-cholesterol diet for 3 months in 36 New Zealand white rabbits. The animals were randomly divided into model group, fluvastatin (10 mg·kg-1·d-1) group, losartan (25 mg·kg-1·d-1) group, and fluvastatin plus losartan group. After the 16-week treatments, the blood samples the animals were collected, and the thoracic aortas were examined immunohistochemically. The mRNA and protein expression levels of monocyte chemotactic protein-1 (MCP-1) were measured using RT-PCR and Western blot. Results: Compared to the treatment with losartan or fluvastatin alone, the combined treatment did not produce higher efficacy in reduction of blood cholesterol level. However, the combination did synergistically decrease the intimal and media thickness of thoracic aortas with significantly reduced macrophage infiltration and MCP-1 expression in the plaques. Conclusion: The combined treatment with losartan and fluvastatin significantly inhibited atherosclerotic progress and reduced inflammation associated with atherosclerotic plaques. PMID:21909126

Immunohistochemical and ultrastructural detection of advanced glycation end products in atherosclerotic lesions of human aorta with a novel specific monoclonal antibody.

PubMed Central

Kume, S.; Takeya, M.; Mori, T.; Araki, N.; Suzuki, H.; Horiuchi, S.; Kodama, T.; Miyauchi, Y.; Takahashi, K.

1995-01-01

To elucidate the deposition of advanced glycation end products (AGEs) in aortic atherosclerosis, aortic walls were obtained from 25 autopsy cases and examined immunohistochemically and immunoelectron microscopically with a monoclonal antibody specific for AGEs, 6D12. Among the autopsy cases, atherosclerotic lesions were found in the aortas of 22 cases and were composed of diffuse intimal thickening, fatty streaks, atherosclerotic plaques, and/or complicated lesions. In these cases, intracellular AGE accumulation was demonstrated in the intimal lesions of aortic atherosclerosis in 12 cases. Compared with the diffuse intimal thickening, intracellular AGE accumulation was marked in the fatty streaks and atherosclerotic plaques. Immunohistochemical double staining with 6D12 and monoclonal antibodies for macrophages or muscle actin or a polyclonal antibody for scavenger receptors demonstrated that the AGE accumulation in macrophages or their related foam cells was marked in the diffuse intimal thickening and fatty streak lesions and that almost all macrophages and macrophage-derived foam cells possessed scavenger receptors. Immunoelectron microscopic observation revealed the localization of 6D12-positive reaction in lysosomal lipid vacuoles or electron-dense granules of the foam cells. These results indicate that AGE accumulation occurs in macrophages, smooth muscle cells, and their related foam cells. Images Figure 2 Figure 3 Figure 6 PMID:7545874

Systolic blood pressure is superior to other haemodynamic predictors of outcome in community acquired pneumonia.

PubMed

Chalmers, J D; Singanayagam, A; Hill, A T

2008-08-01

Admission blood pressure (BP) assessment is a central component of severity assessment for community acquired pneumonia. The aim of this study was to establish which readily available haemodynamic measure on admission is most useful for predicting severity in patients admitted with community acquired pneumonia. A prospective observational study of patients admitted with community acquired pneumonia was conducted in Edinburgh, UK. The measurements compared were systolic and diastolic BP, mean arterial pressure and pulse pressure. The outcomes of interest were 30 day mortality and the requirement for mechanical ventilation and/or inotropic support. Admission systolic BP < 90 mm Hg, diastolic BP < or = 60 mm Hg, mean arterial pressure < 70 mm Hg and pulse pressure < or = 40 mm Hg were all associated with increased 30 day mortality and the need for mechanical ventilation and/or inotropic support on multivariate logistic regression. The AUC values for each predictor of 30 day mortality were as follows: systolic BP < 90 mm Hg 0.70; diastolic BP < or = 60 mm Hg 0.59; mean arterial pressure < 70 mm Hg 0.64; and pulse pressure < or = 40 mm Hg 0.60. The AUC values for each predictor of need for mechanical ventilation and/or inotropic support were as follows: systolic BP < 90 mm Hg 0.70; diastolic BP < or = 60 mm Hg 0.68; mean arterial pressure < 70 mm Hg 0.69; and pulse pressure < or = 40 mm Hg 0.59. A simplified CRB65 score containing systolic blood pressure < 90 mm Hg alone performed equally well to standard CRB65 score (AUC 0.76 vs 0.74) and to the standard CURB65 score (0.76 vs 0.76) for the prediction of 30 day mortality. The simplified CRB65 score was equivalent for prediction of mechanical ventilation and/or inotropic support to standard CRB65 (0.77 vs 0.77) and to CURB65 (0.77 vs 0.78). Systolic BP is superior to other haemodynamic predictors of 30 day mortality and need for mechanical ventilation and/or inotropic support in community acquired pneumonia. The CURB65

Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial - protocol for an observational cohort study.

PubMed

Szymański, Filip M; Gałązka, Zbigniew; Płatek, Anna E; Górko, Dariusz; Ostrowski, Tomasz; Adamkiewicz, Karolina; Łęgosz, Paweł; Ryś, Anna; Semczuk-Kaczmarek, Karolina; Celejewski, Krzysztof; Filipiak, Krzysztof J

2017-01-01

Peripheral arterial disease (PAD) is in fact a group of disease entities with different symptoms and course but a common underlying cause, i.e. atherosclerosis. Atherosclerosis is known to be aggravated by several cardiovascular risk factors, including obstructive sleep apnoea (OSA). Following paper is a protocol for the Peripheral ARtery Atherosclerotic DIsease and SlEep disordered breathing (PARADISE) trial, which aims to describe the prevalence of OSA in PAD patients scheduled for revascularisation, and to determine the effect of OSA on the procedure outcomes. The PARADISE study is an observational cohort trial. It plans to include 200 consecutive patients hospitalised for revascularisation due to PAD. In every patient an overnight sleep study will be performed to diagnose sleep disorders. Accord¬ing to the results of the test, patients will be divided into two groups: group A - patients with OSA, and group B - patients without OSA (control group). All patients will also be screened for classical and non-classical cardiovascular risk factors. In some of the patients, during surgery, a fragment of atherosclerotic plaque will be collected for further testing. Patients will be followed for one year for adverse events and end-points. Primary end-point of the study will be the failure of revascularisa¬tion defined as recurrence or new onset of the symptoms of ischaemia from the treated region, a need for re-operation or procedure revision, or recurrence of ischaemia signs on the imaging tests. The data obtained will help determine the incidence of OSA in the population of patients with PAD. The au¬thors expect to show that, as with other cardiovascular diseases associated with atherosclerosis, also in patients with PAD the incidence of undiagnosed OSA is high and its presence is associated with elevated cholesterol, inflammatory markers, and higher prevalence of arterial hypertension and poor control of other cardiovascular risk factors. In addition, due to

Haemodynamic improvement of older, previously replaced mechanical mitral valves by removal of the subvalvular pannus in redo cardiac surgery.

PubMed

Kim, Jong Hun; Kim, Tae Youn; Choi, Jong Bum; Kuh, Ja Hong

2017-01-01

Patients requiring redo cardiac surgery for diseased heart valves other than mitral valves may show increased pressure gradients and reduced valve areas of previously placed mechanical mitral valves due to subvalvular pannus formation. We treated four women who had mechanical mitral valves inserted greater than or equal to 20 years earlier and who presented with circular pannus that protruded into the lower margin of the valve ring but did not impede leaflet motion. Pannus removal improved the haemodynamic function of the mitral valve. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE−/− Reporter Mouse—Brief Report

PubMed Central

Iqbal, Asif J.; Jones, Daniel; Patel, Jyoti; Coutinho, Patricia; Taylor, Lewis; Greaves, David R.; Channon, Keith M.

2017-01-01

Objective— To create a model of atherosclerosis using green fluorescent protein (GFP)–targeted monocytes/macrophages, allowing analysis of both endogenous GFP+ and adoptively transferred GFP+ myeloid cells in arterial inflammation. Approach and Results— hCD68GFP reporter mice were crossed with ApoE−/− mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II–induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP+ expression in CD11b+/CD64+, CD11c+/MHC-IIHI, and CD11b+/F4/80+ myeloid cells. Adoptive transfer of GFP+ monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2−/− monocytes to sites of inflammation. Conclusions— hCD68GFP/ApoE−/− mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes. PMID:27908893

Physical frailty in older adults is associated with metabolic and atherosclerotic risk factors and cognitive impairment independent of muscle mass.

PubMed

Lee, J S W; Auyeung, T-W; Leung, J; Kwok, T; Leung, P-C; Woo, J

2011-12-01

Metabolic and atherosclerotic diseases are known risk factors for disability in old age, and can result in sarcopenia as well as cognitive impairment, which are both components of frailty syndrome. As muscle loss increases with ageing, it is unclear whether muscle loss per se, or the diseases themselves, are the underlying cause of physical frailty in those suffering from these diseases. We tested the hypothesis that metabolic and atherosclerotic diseases and cognitive impairment are associated with physical frailty independent of muscle loss in old age, and further examined their impact on the relationship between physical frailty and mortality. Prospective. Community. 4000 community dwelling Chinese elderly ≥65 years. Diabetes, hypertension, stroke, heart disease, cognitive impairment, smoking, physical activity, waist hip ratio (WHR) and ankle-brachial index (ABI)) were recorded. Physical frailty measurements (grip-strength, chair-stands, stride length and 6-metre walks) were summarized into a composite frailty score (0-20), 0 being the most frail) according to quartiles of performance. Appendicular muscle mass (ASM) was measured using dual X-ray absorptiometry. Relationships between the score and covariates were analyzed. Cox regression was used to study the impact of metabolic and atnerosclerotic risk factors on the relationship between physical frailty and 6-year mortality. After adjustment for ASM, all metabolic diseases and indexes, and cognitive impairment were significantly associated with the composite physical frailty score in univariate analysis. In multivariate analysis, cognitive impairment, high WHR, diabetes, stroke and heart disease were all independently associated with higher physical frailty with adjustment for age, physical activity level and ASM. Hypertension was associated with physical frailty in men but not in women. In Cox regression, increased physical frailty was associated with higher 6-year mortality. The impact of metabolic and

Real-Time Elastography Visualization and Histopathological Characterization of Rabbit Atherosclerotic Carotid Arteries.

PubMed

Wang, ZhenZhen; Liu, NaNa; Zhang, LiFeng; Li, XiaoYing; Han, XueSong; Peng, YanQing; Dang, MeiZheng; Sun, LiTao; Tian, JiaWei

2016-01-01

To evaluate the feasibility of non-invasive vascular real-time elastography imaging (RTE) in visualizing the composition of rabbit carotid atherosclerotic plaque as determined by histopathology, a rabbit model of accelerated carotid atherosclerosis was used. Thirty rabbits were randomly divided into two groups of 15 rabbits each. The first group was fed a cholesterol-rich diet and received balloon-induced injury the left common carotid artery endothelium, whereas the second group only received a cholesterol-rich diet. The rabbits were all examined in vivo with HITACHI non-invasive vascular real-time elastography (Hi-RTE) at baseline and 12 wk, and results from the elastography were compared with American Heart Association histologic classifications. Hi-RTE and the American Heart Association histologic classifications had good agreement, with weighted Cohen's kappa (95% confidence internal) of 0.785 (0.649-0.920). Strains of segmented plaques that were stained in different colors were statistically different (p < 0.0001). The sensitivity and specificity of elastograms for detecting a lipid core were 95.5% and 61.5%, respectively, and the area under the receiver operating characteristic curve was 0.789, with a 95% confidence interval of 0.679 to 0.876. This study is the first to indicate the feasibility of utilizing Hi-RTE in visualizing normal and atherosclerotic rabbit carotid arteries non-invasively. This affordable and reliable method can be widely applied in research of both animal and human peripheral artery atherosclerosis. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Relationship between aortic valve calcification and the severity of coronary atherosclerotic disease.

PubMed

Qian, Juying; Chen, Zhangwei; Ge, Junbo; Ma, Jianying; Chang, Shufu; Fan, Bing; Liu, Xuebo; Ge, Lei

2010-07-01

Aortic valve calcification (AVC), which has been confirmed to be associated with various risk factors of cardiac disease, is common in the elderly and associated with increased cardiovascular mortality. It has been hypothesized that AVC is associated with coronary atherosclerotic disease, and its severity. Between July 2007 and November 2007, a total of 235 patients with chest pain or chest distress were admitted to the authors' institution for coronary angiography. The severity of coronary atherosclerotic disease (CAD) was evaluated by the Gensini score, the number of stenosed vessels, and the prevalence of total occlusion. All patients underwent transthoracic echocardiography to detect AVC. Patients with CAD had a higher prevalence of AVC than those without CAD (44% versus 26%, p = 0.005). Likewise, the prevalence of AVC was significantly higher in patients with a higher Gensini score than in those with a lower score. Patients with AVC had a higher prevalence of CAD, and higher Gensini scores and numbers of stenosed coronary arteries, even after stratification by age (65 years). On multivariable logistic regression analysis for CAD, the odds ratio (OR) of AVC was 2.315 (95% confidence interval (CI): 1.158-4.629, p = 0.018); this value was higher than that for total cholesterol (OR = 1.637, p = 0.008), lipoprotein-a (OR = 1.003, p = 0.015) and fibrinogen (OR = 1.009, p = 0.006), and marginally less than that for male gender (OR = 2.665, p = 0.005). Patients with AVC had a higher prevalence and greater severity of CAD.

Co-expression of p53 and MDM2 in human atherosclerosis: implications for the regulation of cellularity of atherosclerotic lesions.

PubMed

Ihling, C; Haendeler, J; Menzel, G; Hess, R D; Fraedrich, G; Schaefer, H E; Zeiher, A M

1998-07-01

Atherosclerosis is a fibroproliferative disease of the arterial intima. It was recently found that wild-type p53 (wt p53) accumulates in human atherosclerotic tissue. Wt p53 is a cell cycle regulator involved in DNA repair, DNA synthesis, cell differentiation, and apoptosis and might therefore make an important contribution to the cellularity of atherosclerotic plaques. The product of the MDM2 gene is a nuclear protein which forms a complex with p53, thereby inhibiting the negative regulatory effects of wt p53 on cell cycle progression. In order to address a potential role of the interaction of p53 with MDM2 for the regulation of cellularity in atherosclerotic tissue, 22 carotid atheromatous plaques from patients undergoing endarterectomy were studied to determine the presence of p53 immunoreactivity (IR), MDM2 IR, cell proliferation as evidenced by MIB1/Ki-67 IR and DNA fragmentation by in situ terminal transferase-mediated dUTP 3' end labelling (TUNEL), as a marker for apoptosis. p53 IR localized to areas with evidence of chronic inflammation (22/22) and was observed in virtually all cell types in 68.79 +/- 7.51 per cent of the nuclei. p53 staining in the control tissue from human internal mammary arteries was present in 0.2 +/- 0.29 per cent of the cells (P < or = 0.002). MDM2 IR was present in all cases (22/22) in macrophages and smooth muscle cells (SMCs) in 60.53 +/- 8.32 per cent of the nuclei (controls: 0.8 +/- 0.65 per cent, P < or = 0.002) and co-localized with p53 IR as shown by examination of adjacent sections and by double immunofluorescence labelling. Importantly, co-immunoprecipitation and western blot analysis revealed that p53 and MDM2 were physically associated, indicating that MDM2-p53 complex formation takes place in vivo in human atherosclerotic tissue. Positive TUNEL staining and MIB1/Ki-67 IR present in 3.01 +/- 1.27 per cent of the nuclei (controls: 0 per cent, P < or = 0.002) localized to the same plaque compartments as p53 IR and MDM2 IR

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study.

PubMed

Kundel, Vaishnavi; Trivieri, Maria Giovanna; Karakatsanis, Nicolas A; Robson, Phillip M; Mani, Venkatesh; Kizer, Jorge R; Kaplan, Robert; Fayad, Zahi; Shah, Neomi

2018-03-05

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging - hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer-before and after continuous positive airway pressure (CPAP). Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3-6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP. Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR mean ) and 6.2% (TBR max ) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others). We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

The Interleukin-6 Gene Promoter Polymorphism -174 and Atherosclerotic Events in Overweight Transplanted Patients

PubMed Central

Bamoulid, Jamal; Courivaud, Cécile; Deschamps, Marina; Gaugler, Béatrice; Tiberghien, Pierre; Chalopin, Jean-Marc; Saas, Philippe; Ducloux, Didier

2011-01-01

Chronic inflammation plays a pivotal role in atherosclerosis. We hypothesized that combining overweight and a greater genetic capacity to produce IL-6 predicted by IL-6 gene promoter polymorphism at position -174 (G→C) may allow to identify individuals exhibiting higher IL-6 and C-reactive protein (CRP) concentrations with a higher risk of atherosclerotic events (AE). The occurrence of AE was analyzed with respect to body mass index, IL-6 gene promoter polymorphism at position -174 (G→C), and other relevant risk factors, retrospectively, in 217 renal transplant recipients and, prospectively, in 132. Circulating IL-6 concentrations were closely related to BMI (r = 0.55, P = .0005). In overweight patients, serum IL-6 concentration was found to be significantly lower in C carriers than in GG patients (4.2 [1.0–5.1] versus 7.3 pg/mL [4.4–100]; P = .025). The incidence of AE was higher in overweight GG patients (29.5% versus 10.1%; P = .0003). In multivariate analysis, overweight-GG had an increased risk to develop AE (HR 2.96 [95% CI 1.09–8.04], P = .034 in the retrospective cohort, and HR 2.99 [95% CI 0.92–9.33], P = .069 in the prospective cohort). All these data are consistent with a role for both genetic and environmental determinants of inflammation (white adipose tissue mass) in the development of AE in renal transplanted patients. PMID:21766010

Effect of Hemodynamics on Stroke Risk in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease.

PubMed

Amin-Hanjani, Sepideh; Pandey, Dilip K; Rose-Finnell, Linda; Du, Xinjian; Richardson, DeJuran; Thulborn, Keith R; Elkind, Mitchell S V; Zipfel, Gregory J; Liebeskind, David S; Silver, Frank L; Kasner, Scott E; Aletich, Victor A; Caplan, Louis R; Derdeyn, Colin P; Gorelick, Philip B; Charbel, Fady T

2016-02-01

Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk. To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke. A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015. Standard medical management of stroke risk factors. The primary outcome was VB-territory stroke. Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors

Relative myotoxic and haemodynamic effects of the β-agonists fenoterol and clenbuterol measured in conscious unrestrained rats

PubMed Central

Burniston, Jatin G; Tan, Lip-Bun; Goldspink, David F

2007-01-01

The β2-adrenoceptor (β2-AR) agonists clenbuterol and fenoterol have similar beneficial effects in animal models of heart failure. However, large doses of clenbuterol can induce cardiomyocyte death and it is not known which of these agents has the most favourable therapeutic profile. We have investigated the cardiotoxicity of clenbuterol and fenoterol alongside that of isoproterenol, and compared their haemodynamic effects. Wistar rats (n=6, per group) were subcutaneously injected with each β-agonist (0.003 mmol kg−1 to 3 mmol kg−1) or saline and cardiomyocyte apoptosis was detected by caspase 3 immunohistochemistry. In a separate experiment rats (n=4) were given equivalent doses to those used in the myotoxicity studies, in a randomised crossover design, and their blood pressure recorded via radio telemetry. Injection of 0.3 mmol kg−1 fenoterol or isoproterenol, but not clenbuterol, induced significant cardiomyocyte apoptosis (0.4±0.05%; P<0.05). At 3 mmol kg−1, all agonists induced apoptosis (fenoterol 1.1±0.1%; isoproterenol 0.9±0.8%; clenbuterol 0.4±0.07%; P<0.05). β1-AR antagonism (10 mg kg−1 bisoprolol) prevented (92%; P<0.05) apoptosis induced by all 3 agonists, but clenbuterol-induced apoptosis could also be prevented (96%; P<0.05) by β2-AR antagonism (10 mg kg−1 ICI118551). Clenbuterol decreased diastolic (1.3-1.6 fold; P<0.05) and systolic (1.3 fold; P<0.05) blood pressure and doses >0.3 mmol kg−1 increased heart rate (1.4 fold; P<0.05). Fenoterol increased heart rate (1.2-1.4 fold; P<0.05) and doses >0.3 mmol kg−1 decreased diastolic blood pressure (1.3 fold; P<0.05). In conclusion, the cardiotoxicity of fenoterol was similar to isoproterenol and greater than clenbuterol, and fenoterol had less desirable haemodynamic effects. PMID:16973691

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

PubMed

Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-04-01

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats

PubMed Central

Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall. PMID:29085605

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

PubMed

Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery

PubMed Central

Qi, Ji; Zhang, Lei; Chen, Chao; Mondal, Shubhro; Ping, Kaike; Chen, Yili

2017-01-01

Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM. PMID:28303160

Recent Advances in Fluorescent Angioscopy for Molecular Imaging of Human Atherosclerotic Coronary Plaque

PubMed Central

2017-01-01

Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques. Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA. Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and antiatherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques. PMID:28381766

Comparison of Gadofluorine-M and Gd-DTPA for Non-Invasive Staging of Atherosclerotic Plaque Stability Using MRI

PubMed Central

Ronald, John A.; Chen, Yuanxin; Belisle, Andre J.-L.; Hamilton, Amanda M.; Rogers, Kem A.; Hegele, Robert A.; Misselwitz, Bernd; Rutt, Brian K.

2009-01-01

Background Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. Here we determined the utility of the MR contrast agent Gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. Methods and Results 5 control and 7 atherosclerotic rabbits were sequentially imaged following administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T1-weighted pulse sequence on a 3T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values following GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours post-injection, but not Gd-DTPA at peak enhancement, was shown to correlate with a quantitative histological morphology index related to these two plaque features. Conclusions GdF-enhanced MRI of atherosclerotic plaques allows non-invasive quantitative information about plaque composition to be acquired at multiple time points post-injection (within 1 and up to 24 hours post-injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events. PMID:19808597

Application of the laguerre deconvolution method for time-resolved fluorescence spectroscopy to the characterization of atherosclerotic plaques.

PubMed

Jo, J A; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J; Marcu, L

2005-01-01

This study investigates the ability of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) to detect inflammation in atherosclerotic lesion, a key feature of plaque vulnerability. A total of 348 TR-LIFS measurements were taken from carotid plaques of 30 patients, and subsequently analyzed using the Laguerre deconvolution technique. The investigated spots were classified as Early, Fibrotic/Calcified or Inflamed lesions. A stepwise linear discriminant analysis algorithm was developed using spectral and TR features (normalized intensity values and Laguerre expansion coefficients at discrete emission wavelengths, respectively). Features from only three emission wavelengths (390, 450 and 500 nm) were used in the classifier. The Inflamed lesions were discriminated with sensitivity > 80% and specificity > 90 %, when the Laguerre expansion coefficients were included in the feature space. These results indicate that TR-LIFS information derived from the Laguerre expansion coefficients at few selected emission wavelengths can discriminate inflammation in atherosclerotic plaques. We believe that TR-LIFS derived Laguerre expansion coefficients can provide a valuable additional dimension for the detection of vulnerable plaques.

No evidence of association between NOD2/CARD15 gene polymorphism and atherosclerotic events after renal transplantation

PubMed Central

Courivaud, Cécile; Ferrand, Christophe; Deschamps, Marina; Tiberghien, Pierre; Chalopin, Jean-Marc; Duperrier, Anne; Saas, Philippe; Ducloux, Didier

2006-01-01

Stable renal transplant recipients (RTR) display high rates of atherosclerotic events (AE). Innate immunity and especially vascular inflammation play a role in the pathogenesis of atherosclerosis. It is illustrated both by an increased occurrence of post-renal transplant cardiovascular events in patients with elevated levels of C-reactive protein and by a correlation between post-transplant AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro-inflammatory activity and macrophage is present in early atherosclerotic lesions. The incidence of single nucleotide polymorphism (SNP) in the three major polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR and the correlation between such polymorphism and the development of AE was analyzed. No correlation was observed between NOD2 gene polymorphism and the occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does not appear to influence cardiovascular complications in RTR. PMID:16641610

Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

PubMed

Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

2018-06-07

AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

Quantification In Situ of Crystalline Cholesterol and Calcium Phosphate Hydroxyapatite in Human Atherosclerotic Plaques by Solid-State Magic Angle Spinning NMR

PubMed Central

Guo, Wen; Morrisett, Joel D.; DeBakey, Michael E.; Lawrie, Gerald M.; Hamilton, James A.

2010-01-01

Because of renewed interest in the progression, stabilization, and regression of atherosclerotic plaques, it has become important to develop methods for characterizing structural features of plaques in situ and noninvasively. We present a nondestructive method for ex vivo quantification of 2 solid-phase components of plaques: crystalline cholesterol and calcium phosphate salts. Magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra of human carotid endarterectomy plaques revealed 13C resonances of crystalline cholesterol monohydrate and a 31P resonance of calcium phosphate hydroxyapatite (CPH). The spectra were obtained under conditions in which there was little or no interference from other chemical components and were suitable for quantification in situ of the crystalline cholesterol and CPH. Carotid atherosclerotic plaques showed a wide variation in their crystalline cholesterol content. The calculated molar ratio of liquid-crystalline cholesterol to phospholipid ranged from 1.1 to 1.7, demonstrating different capabilities of the phospholipids to reduce crystallization of cholesterol. The spectral properties of the phosphate groups in CPH in carotid plaques were identical to those of CPH in bone. 31P MAS NMR is a simple, rapid method for quantification of calcium phosphate salts in tissue without extraction and time-consuming chemical analysis. Crystalline phases in intact atherosclerotic plaques (ex vivo) can be quantified accurately by solid-state 13C and 31PMAS NMR spectroscopy. PMID:10845882

Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

PubMed

Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-04-01

Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0�

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

PubMed

Aguilar, Edenil C; Santos, Lana Claudinez Dos; Leonel, Alda J; de Oliveira, Jamil Silvano; Santos, Elândia Aparecida; Navia-Pelaez, Juliana M; da Silva, Josiane Fernandes; Mendes, Bárbara Pinheiro; Capettini, Luciano S A; Teixeira, Lilian G; Lemos, Virginia S; Alvarez-Leite, Jacqueline I

2016-08-01

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

PubMed Central

Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

2016-01-01

Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

NASA Astrophysics Data System (ADS)

McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

2015-02-01

Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging.

PubMed

Meletta, Romana; Müller Herde, Adrienne; Chiotellis, Aristeidis; Isa, Malsor; Rancic, Zoran; Borel, Nicole; Ametamey, Simon M; Krämer, Stefanie D; Schibli, Roger

2015-01-27

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging.

Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits

PubMed Central

Castelo-Branco, Camil; Sanjuán, Alex; Ascaso, Carles; Colodrón, Marta; Blümel, Juan Enrique; Casals, Elena; Ordi, Jaume; Vanrell, Juan Antonio

2003-01-01

BACKGROUND: Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known. OBJECTIVE: To investigate the effect of tibolone therapy on aorta atherogenesis. MATERIAL AND METHODS: Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S). RESULTS: After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17±0.72 mmol/L to 35.36±9.01 mmol/L, in group S from 2.88±0.9 mmol/L to 28.76±9.442 mmol/L, in group E from 1.69±0.44 mmol/L to 1.69±0.44 mmol/L and in group T from 2.03±0.22 mmol/L to 26.33±13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47±12.2%, 24.51±16.1%, 17.91±10.19% and 10.21±6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups). CONCLUSION: The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels. PMID:19644583

Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

PubMed

Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

2011-07-01

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

Effects of scalp block with bupivacaine versus levobupivacaine on haemodynamic response to head pinning and comparative efficacies in postoperative analgesia: A randomized controlled trial.

PubMed

Can, Banu O; Bilgin, Hülya

2017-04-01

Objective This study was performed to determine the effects of scalp blocks with bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy and the efficacies and analgesic requirements of these drugs postoperatively. Methods This randomized, prospective, placebo-controlled, double-blind study included 90 patients (age, 18-85 years; American Society of Anesthesiologists physical status, I or II). The patients were randomly divided into three groups: those who received 20 mL of 0.5% bupivacaine (Group B, n = 30), 20 mL of 0.5% levobupivacaine (Group L, n = 30), or saline as a placebo (Group C, n = 30). Scalp blocks were performed 5 min before head pinning. The primary outcome was the mean arterial pressure (MAP), and the secondary outcomes were the heart rate (HR), visual analogue scale (VAS) scores, and additional intraoperative and postoperative drug use. Postoperative pain was evaluated using a 10-cm VAS. Results During head pinning and incision, the MAP and HR were significantly higher in Group C. The additional drug requirement for intraoperative hypertension and tachycardia was significantly higher in Group C. There were no significant differences in MAP, HR, or VAS scores between Groups B and L. Conclusion Both bupivacaine and levobupivacaine can be effectively and safely used for scalp blocks to control haemodynamic responses and postoperative pain.

Vorapaxar in atherosclerotic disease management.

PubMed

Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

2015-05-01

To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells.

PubMed

Saleh Al-Shehabi, Tuqa; Iratni, Rabah; Eid, Ali H

2016-10-15

Cardiovascular disease (CVD) remains the leading cause of global death, with atherosclerosis being a major contributor to this mortality. Several mechanisms are implicated in the pathogenesis of this disease. A key element in the development and progression of atherosclerotic lesions is the phenotype of vascular smooth muscle cells. Under pathophysiologic conditions such as injury, these cells switch from a contractile to a synthetic phenotype that often possesses high proliferative and migratory capacities. Despite major advances made in the management and treatment of atherosclerosis, mortality associated with this disease remains high. This mandates that other approaches be sought. Herbal medicine, especially for the treatment of CVD, has been gaining more attention in recent years. This is in no small part due to the evidence-based values associated with the consumption of many plants as well as the relatively cheaper prices, easier access and conventional folk medicine "inherited" over generations. Sections: In this review, we provide a brief introduction about the pathogenesis of atherosclerosis then we highlight the role of vascular smooth muscle cells in this disease, especially when a phenotypic switch of these cells arises. We then thoroughly discuss the various plants that show potentially beneficial effects as anti-atherosclerotic, with prime attention given to herbs and plants that inhibit the phenotypic switch of vascular smooth muscle cells. Accumulating evidence provides the justification for the use of botanicals in the treatment or prevention of atherosclerosis. However, further studies, especially clinical ones, are warranted to better define several pharmacological parameters of these herbs, such as toxicity, tolerability, and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studies of the haemodynamic effects of creatine phosphate in man.

PubMed Central

Hurlow, R A; Aukland, A; Hardman, J; Whittington, J R

1982-01-01

1 The haemodynamic effects of intravenous creatine phosphate 1000 mg have been studied. 2 During the first 60 min following drug administration heart rate and blood pressure did not change but cardiac output fell significantly by approximately 18%. Calculated total peripheral resistance showed a corresponding significant rise, the maximum increase being approximately 24%. All these changes were beginning to diminish within 90 min after the injection. 3 Total limb blood flow measured in both arm and leg (using venous occlusion strain-gauge plethysmography) showed no appreciable changes following injection of creatine phosphate. 4 There was a progressive reduction in leg muscle blood flow (Xe133 clearance method) following injection which was statistically significant with respect to the initial level and reached a minimum (46% reduction) 50 min after the injection. 5 Skin blood flow, estimated by infra-red photoplethysmography, showed changes complementary to those seen with muscle flow. There was a progressive and significant rise to a peak (73% increase) 30 min after the injection. 6 No adverse reactions to the injections were noted. 7 Reduced cardiac output in the absence of altered total limb blood flow presumably reflects a reduction in visceral blood flow, which was not measured in this study. Within the limbs, creatine phosphate appears to result in a redistribution of blood flow from muscle to skin. Thus, these preliminary results suggest that intravenous creatine phosphate could be clinically useful in situations where short term improvement in skin blood flow would be advantageous and that further controlled studies would be justified. PMID:7093109

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Barlic-Dicen, Jana

2013-01-01

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events. PMID:23538778

Haemodynamic Variations of Flow to Renal Arteries in Custom-Made and Pivot Branch Fenestrated Endografting.

PubMed

Ou, J; Tang, A Y S; Chiu, T L; Chow, K W; Chan, Y C; Cheng, S W K

2017-01-01

This study aimed to investigate variation of blood flow to renal arteries in custom-made and pivot branch (p-branch) fenestrated endografting, using a computational fluid dynamics (CFD) technique. Idealised models of custom-made and p-branch fenestrated grafting were constructed on a basis of a 26 mm stent graft. The custom-made fenestration was designed with a 6 mm diameter, while the 5 mm depth renal p-branch was created with a 6 mm inner and 15 mm outer fenestration. Two configurations (option A and option B) were constructed with different locations of p-branches. Option A had both renal p-branches at the same level, whereas option B contained two staggered p-branches at lower positions. The longitudinal stent orientation in both custom-made and p-branch models was represented by a takeoff angle (ToA) between the renal stent and distal stent graft centreline, varying from 55° to 125°. Computational simulations were performed with realistic boundary conditions governing the blood flow. In both custom-made and p-branch fenestrated models, the flow rate and wall shear stress (WSS) were generally higher and recirculation zones were smaller when the renal stent faced caudally. In custom-made models, the highest flow rate (0.390 L/min) was detected at 70° ToA and maximum WSS on vessel segment (16.8 Pa) was attained at 55° ToA. In p-branch models, option A and option B displayed no haemodynamic differences when having the same ToA. The highest flow rate (0.378 L/min) and maximum WSS on vessel segment (16.7 Pa) were both calculated at 55° ToA. The largest and smallest recirculation zones occurred at 90° and 55° ToA respectively in both custom-made and p-branch models. Custom-made fenestrated models exhibited consistently higher flow rate and shear stress and smaller recirculation zones in renal arteries than p-branch models at the same ToA. Navigating the renal stents towards caudal orientation can achieve better haemodynamic outcomes in both

Haemodynamic changes in ipsilateral and contralateral fingers caused by acute exposures to hand transmitted vibration.

PubMed Central

Bovenzi, M; Griffin, M J

1997-01-01

OBJECTIVES: To investigate changes in digital circulation during and after exposure to hand transmitted vibration. By studying two frequencies and two magnitudes of vibration, to investigate the extent to which haemodynamic changes depend on the vibration frequency, the vibration acceleration, and the vibration velocity. METHODS: Finger skin temperature (FST), finger blood flow (FBF), and finger systolic pressure were measured in the fingers of both hands in eight healthy men. Indices of digital vasomotor tone-such as critical closing pressure and vascular resistance-were estimated by pressure-flow curves obtained with different hand heights. With a static load of 10 N, the right hand was exposed for 30 minutes to each of the following root mean squared (rms) acceleration magnitudes and frequencies of vertical vibration: 22 m.s-2 at 31.5 Hz, 22 m.s-2 at 125 Hz, and 87 m.s-2 at 125 Hz. A control condition consisted of exposure to the static load only. The measures of digital circulation and vasomotor tone were taken before exposure to the vibration and the static load, and at 0, 20, 40, and 60 minutes after the end of each exposure. RESULTS: Exposure to static load caused no significant changes in FST, FBF, or indices of vasomotor tone in either the vibrated right middle finger or the non-vibrated left middle finger. In both fingers, exposure to vibration of 125 Hz and 22 m.s-2 produced a greater reduction in FBF and a greater increase in vasomotor tone than did vibration of 31.5 Hz and 22 m.s-2. In the vibrated right finger, exposure to vibration of 125 Hz and 87 m.s-2 provoked an immediate vasodilation which was followed by vasoconstriction during recovery. The non-vibrated left finger showed a significant increase in vasomotor tone throughout the 60 minute period after the end of vibration exposure. CONCLUSIONS: The digital circulatory response to acute vibration depends upon the magnitude and frequency of the vibration stimulus. Vasomotor mechanisms, mediated

TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE−/− mice

PubMed Central

Prasad, Sakamuri Siva Sankara Vara; Higashi, Yusuke; Sukhanov, Sergiy; Siddesha, Jalahalli M; Delafontaine, Patrice; Siebenlist, Ulrich; Chandrasekar, Bysani

2016-01-01

Background and aims Atherosclerosis is a major cause of heart attack and stroke. Inflammation plays a critical role in the development of atherosclerosis. Since the cytoplasmic adaptor molecule TRAF3IP2 (TRAF3-Interacting Protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that TRAF3IP2 mediates atherosclerotic plaque development. Methods TRAF3IP2/ApoE double knockout (DKO) mice were generated by crossing TRAF3IP2−/− and ApoE−/− mice. ApoE−/− mice served as controls. Both DKO and control mice were fed a high-fat diet for 12 weeks. Plasma lipids were measured by ELISA, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell content by histomorphometry, and aortic gene expression by RT-qPCR. Results The plasma lipoprotein profile was not altered by TRAF3IP2 gene deletion in ApoE−/− mice. While total aortic plaque area was decreased in DKO female, but not male mice, the plaque necrotic area was significantly decreased in DKO mice of both genders. Plaque collagen and smooth muscle cell contents were increased significantly in both female and male DKO mice compared to respective controls. Aortic expression of proinflammatory cytokine (Tumor necrosis factor α, TNFα), chemokine (Chemokine (C-X-C motif) Ligand 1, CXCL1) and adhesion molecule (Vascular cell adhesion molecule 1, VCAM1; and Intercellular adhesion molecule 1, ICAM1) gene expression were decreased in both male and female DKO mice. In addition, the male DKO mice showed a markedly reduced expression of extracellular matrix (ECM)-related genes, including TIMP1 (Tissue inhibitor of metalloproteinase 1), RECK (Reversion-Inducing- Cysteine-Rich Protein with Kazal Motifs) and ADAM17 (A Disintegrin And Metalloproteinase 17). Conclusions TRAF3IP2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the

Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions.

PubMed Central

Jaakkola, O.; Nikkari, T.

1990-01-01

Lipoprotein metabolism and cholesterol accumulation in atherosclerotic lesions was studied using enzymatically isolated primary cell cultures from aortas of rabbits made atherosclerotic by cholesterol feeding. The cultures consisted of macrophages and smooth muscle cells, thus resembling, in composition, fatty streak lesions. The mean (+/- SD) cholesteryl ester content of the dispersed cells was 1059 +/- 445 micrograms/mg cell protein, but it declined steeply during 1 week in primary culture. The uptake of low-density lipoprotein (LDL), beta-migrating very low-density lipoprotein (beta-VLDL), and acetylated LDL (acetyl-LDL), labeled with 125I or with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine (DiI), was studied in 2-day-old primary cultures. DiI-acetyl-LDL was avidly taken up by the macrophages and, to a lesser extent, by some smooth muscle cells. The uptake of DiI-beta-VLDL by the macrophages was weaker and less homogeneous than that of DiI-acetyl-LDL. The degradation rates of 125I-labeled beta-VLDL, LDL and acetyl-LDL were 135 +/- 54, 195 +/- 20, and 697 +/- 14 ng/mg cell protein/8 hours, respectively. Incubation with unlabeled acetyl-LDL enhanced the incorporation of [3H]oleate into cholesteryl esters and increased the cellular cholesteryl ester content. These results suggest that arterial macrophages and, to some extent, smooth muscle cells from cholesterol-fed rabbits actively metabolize acetyl-LDL and are thus capable of accumulating cholesteryl esters by uptake of modified forms of LDL. Images Figure 2 PMID:2201201

Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques

PubMed Central

Yu, Shann S.; Ortega, Ryan A.; Reagan, Brendan W.; McPherson, John A.; Sung, Hak-Joon; Giorgio, Todd D.

2017-01-01

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of ‘Vulnerable atherosclerotic plaques’. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition—which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician’s toolbox—decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques. PMID:21834059

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

PubMed

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.

PubMed

Mitsiou, Eudoxia; Boutari, Chrysoula; Kotsis, Vasilios; Georgianou, Eleni; Doumas, Michael; Karagiannis, Asterios; Athyros, Vasilios G

2018-01-01

Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of organic and inorganic nitrate on aortic and carotid haemodynamics in heart failure with preserved ejection fraction.

PubMed

Chirinos, Julio A; Londono-Hoyos, Francisco; Zamani, Payman; Beraun, Melissa; Haines, Philip; Vasim, Izzah; Varakantam, Swapna; Phan, Timothy S; Cappola, Thomas P; Margulies, Kenneth B; Townsend, Raymond R; Segers, Patrick

2017-11-01

To assess the haemodynamic effects of organic vs. inorganic nitrate administration among patients with heart failure with preserved ejection fraction (HFpEF). We assessed carotid and aortic pressure-flow relations non-invasively before and after the administration of 0.4 mg of sublingual nitroglycerin (n = 26), and in a separate sub-study, in response to 12.9 mmoL of inorganic nitrate (n = 16). Nitroglycerin did not consistently reduce wave reflections arriving at the proximal aorta (change in real part of reflection coefficient, 1st harmonic: -0.09; P = 0.01; 2nd harmonic: -0.045, P = 0.16; 3rd harmonic: +0.087; P = 0.05), but produced profound vasodilatation in the carotid territory, with a significant reduction in systolic blood pressure (133.6 vs. 120.5 mmHg; P = 0.011) and a marked reduction in carotid bed vascular resistance (19 580 vs. 13 078 dynes · s/cm 5 ; P = 0.001) and carotid characteristic impedance (3440 vs. 1923 dynes · s/cm 5 ; P = 0.002). Inorganic nitrate, in contrast, consistently reduced wave reflections across the first three harmonics (change in real part of reflection coefficient, 1st harmonic: -0.12; P = 0.03; 2nd harmonic: -0.11, P = 0.01; 3rd harmonic: -0.087; P = 0.09) and did not reduce blood pressure, carotid bed vascular resistance, or carotid characteristic impedance (P = NS). Nitroglycerin produces marked vasodilatation in the carotid circulation, with a pronounced reduction in blood pressure and inconsistent effects on central wave reflections. Inorganic nitrate, in contrast, produces consistent reductions in wave reflections, and unlike nitroglycerin, it does so without significant hypotension or cerebrovascular dilatation. These haemodynamic differences may underlie the different effects on exercise capacity and side effect profile of inorganic vs. organic nitrate in HFpEF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

PubMed

Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

2016-04-01

Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations.

Is triglyceride/HDL ratio a reliable screening test for assessment of atherosclerotic risk in patients with chronic inflammatory disease?

PubMed

Keles, Nursen; Aksu, Feyza; Aciksari, Gonul; Yilmaz, Yusuf; Demircioglu, Kenan; Kostek, Osman; Cekin, Muhammed Esad; Kalcik, Macit; Caliskan, Mustafa

2016-01-01

The term chronic inflammatory disease (CID) refers to a category of inflammatory diseases that includes Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF). The incidence of adverse cardiovascular events is greater among patients with CID, though they may not have conventional atherosclerotic risk factors. Endothelial dysfunction is one of the underlying fundamental mechanisms that trigger development of atherosclerotic alterations in arteries, and flow-mediated dilatation (FMD) is a noninvasive method to determine endothelial dysfunction. Recent studies have shown a relationship between high triglyceride high-density lipoprotein cholesterol (TG/HDL-C) ratio and coronary atherosclerosis. Many studies have demonstrated that patients with CID have lower FMD values compared to healthy population, indicating endothelial dysfunction. However TG/HDL ratio and its relationship to FMD in patients with CID has not been investigated. The present study investigated whether TG/HDL ratio in CID patients differs from that of healthy population, and its relationship to FMD in patients with CID. A total of 58 patients with CID and a group of 58 healthy volunteer individuals were enrolled in the study. FMD measurements were taken with high resolution ultrasound (US), and TG/HDL ratios were calculated. Patients with CID had significantly higher TG/HDL-C ratio (2.5 [2.2-2.8] vs 2.3 [2.1-2.5]; p=0.03) and lower FMD values (5.2 [4.2-6.3] vs 6.7 [6.3-9.7]; p<0.001), compared to healthy group, and a negative correlation was found between FMD levels and TG/HDL ratio of the study population. Higher TG/HDL ratio and lower FMD values found in CID patients may reflect increased atherosclerotic risk.

Effects of high-intensity interval training on central haemodynamics and skeletal muscle oxygenation during exercise in patients with chronic heart failure.

PubMed

Spee, Ruud F; Niemeijer, Victor M; Wijn, Pieter F; Doevendans, Pieter A; Kemps, Hareld M

2016-12-01

Background High-intensity interval training (HIT) improves exercise capacity in patients with chronic heart failure (CHF). Moreover, HIT was associated with improved resting cardiac function. However, the extent to which these improvements actually contribute to training-induced changes in exercise capacity remains to be elucidated. Therefore, we evaluated the effects of HIT on exercising central haemodynamics and skeletal muscle oxygenation. Methods Twenty-six CHF patients were randomised to a 12-week 4 × 4 minute HIT program at 85-95% of peak VO 2 or usual care. Patients performed maximal and submaximal cardiopulmonary exercise testing with simultaneous assessment of cardiac output and skeletal muscle oxygenation by near infrared spectroscopy, using the amplitude of the tissue saturation index (TSIamp). Results Peak workload increased by 11% after HIT ( p between group = 0.01) with a non-significant increase in peak VO 2 (+7%, p between group = 0.19). Cardiac reserve increased by 37% after HIT ( p within group = 0.03, p between group = 0.08); this increase was not related to improvements in peak workload. Oxygen uptake recovery kinetics after submaximal exercise were accelerated by 20% ( p between group = 0.02); this improvement was related to a decrease in TSIamp ( r = 0.71, p = 0.03), but not to changes in cardiac output kinetics. Conclusion HIT induced improvements in maximal exercise capacity and exercising haemodynamics at peak exercise. Improvements in recovery after submaximal exercise were associated with attenuated skeletal muscle deoxygenation during submaximal exercise, but not with changes in cardiac output kinetics, suggesting that the effect of HIT on submaximal exercise capacity is mediated by improved microvascular oxygen delivery-to-utilisation matching.

64Cu-Labeled LyP-1-Dendrimer for PET-CT Imaging of Atherosclerotic Plaque

PubMed Central

2015-01-01

The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [18F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with 64Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE–/–) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-64Cu than the (ARAL)4-dendrimer-64Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-64Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-64Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in

Discoidin Domain Receptor-1 Deficiency Attenuates Atherosclerotic Calcification and Smooth Muscle Cell-Mediated Mineralization

PubMed Central

Ahmad, Pamela J.; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y.; Giachelli, Cecilia M.; Bendeck, Michelle P.

2009-01-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1−/−;Ldlr−/− and Ddr1+/+;Ldlr−/− mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor α staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1+/+ smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1−/− smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification. PMID:19893047

Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization.

PubMed

Ahmad, Pamela J; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y; Giachelli, Cecilia M; Bendeck, Michelle P

2009-12-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1(-/-);Ldlr(-/-) and Ddr1(+/+);Ldlr(-/-) mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor alpha staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1(+/+) smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1(-/-) smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification.

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation

PubMed Central

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F.; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2015-01-01

Objective CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). Methods and Results CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse “flow cessation model,” in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. Conclusions These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

PubMed

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2015-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

The role of urotensin II and atherosclerotic risk factors in patients with slow coronary flow

PubMed Central

Şatıroğlu, Ömer; Emre Durakoğlugil, Murtaza; Çetin, Mustafa; Çiçek, Yüksel; Erdoğan, Turan; Duman, Hakan

2016-01-01

Background Slow coronary flow (SCF) is an angiographic finding characterized with delayed opacification of epicardial coronary arteries without obstructive coronary disease. Urotensin II (UII) is an important vascular peptide, which has an important role in hypertension, coronary artery disease, and vascular remodeling in addition to potent vasoconstrictor effect. Objectives We investigated UII levels, hypertension, and other atherosclerotic risk factors in patients with SCF, a variety of coronary artery disease. Methods We enrolled 14 patients with SCF and 29 subjects with normal coronary arteries without SCF. We compared the UII levels and the atherosclerotic risk factors between patients with SCF and control subjects with normal coronary flow. Results UII concentrations were significantly higher in patients with SCF compared to controls (711.0 ± 19.4 vs. 701.5 ± 27.2 ng/mL, p = 0.006). We detected a positive correlation between SCF and age (r = 0.476, p = 0.001), BMI (r = 0.404, p = .002), UII concentrations (r = 0.422, p = 0.006), and hypertension (r = 0.594, p = 0.001). Conclusion We identified increased UII levels in patients with SCF. We think that UII concentrations may be informative on SCF pathogenesis due to relationship with inflammation, atherosclerosis, and vascular remodeling. PMID:28180005

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

PubMed

Veiner, Hilla-Lee; Gorbatov, Rostic; Vardi, Moshe; Doros, Gheorghe; Miller-Lotan, Rachel; Zohar, Yaniv; Sabo, Edmond; Asleh, Rabea; Levy, Nina S; Goldfarb, Levi J; Berk, Thomas A; Haas, Tali; Shalom, Hadar; Suss-Toby, Edith; Kam, Adi; Kaplan, Marielle; Tamir, Ronit; Ziskind, Anna; Levy, Andrew P

2015-03-01

Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

PubMed

Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

2015-06-01

Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

Elucidation of the atherosclerotic disease process in apo E and wild type mice by vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Adar, Fran; Jelicks, Linda; Naudin, Coralie; Rousseau, Denis; Yeh, Syun-ru

2004-07-01

Raman and FTIR microprobe spectroscopy have been used to characterize the atherosclerotic process in Apo E and wild type mice. The Apo E null mouse is being studied in parallel with a healthy strain as a model of the human atherosclerotic disease. Preliminary Raman microprobe spectra have been recorded from the lumen of the aorta vessels from a normal black mouse (C57BL/6J) and the apo E null mouse fed on a normal chow diet. Spectra were also recorded from another normal mouse fed breeder chow containing a much higher content of fats. In the Raman spectra the fat cells exhibited spectra typical of esterified triglycerides while the wall tissue had spectra dominated by Amide I and III modes and the phenylalanine stretch at 1003 cm-1 of protein. The FTIR spectra showed the typical Amide I and II bands of protein and the strong >C=O stretch of the triglycerides. In addition, there were morphologically distinct regions of the specimens indicating a surprising form of calcification in one very old mouse (wild type), and free fatty acid inclusions in the knock out mouse. The observation of these chemistries provide new information for elucidation of the molecular mechanisms of the development of atherosclerosis.

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

PubMed Central

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-01-01

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model. PMID:19638223

Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet.

PubMed

Sivak, Olena; Darlington, Jerry; Gershkovich, Pavel; Constantinides, Panayiotis P; Wasan, Kishor M

2009-07-28

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.

Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: Synopsis of the 2013 ACC/AHA cholesterol guideline

USDA-ARS?s Scientific Manuscript database

Atherosclerotic cardiovascular disease (ASCVD) is the leading U.S. cause of death, lost quality of life and medical costs. Nearly one in three Americans die from heart disease and stroke. Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure...

PaCO2 measurement in cerebral haemodynamics: face mask or nasal cannulae?

PubMed

Minhas, J S; Robinson, T; Panerai, R

2017-06-22

PaCO 2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the effects of CO 2 measurement technique on cerebrovascular parameters are unknown. In order to determine if the two most commonly used approaches, face mask (FM) or nasal cannulae (NC), are interchangeable or not, we tested the hypothesis that the use of FM versus NC does not lead to significant differences in CO 2 -related systemic and cerebrovascular parameters. Recordings of CBF velocity (CBFV), blood pressure (BP), heart rate, and end-tidal CO 2 (EtCO 2 ) were performed in 42 subjects during normocapnia (FM or NC) and 5% CO 2 inhalation (FM) or hyperventilation (NC). Dynamic cerebral autoregulation was assessed with the autoregulation index (ARI), derived by transfer function analysis from the CBFV response to a hypothetical step change in BP. Significant differences in physiological parameters were seen between FM and NC: EtCO 2 (37.40 versus 35.26 mmHg, p  =  0.001) and heart rate (69.6 versus 66.7 bpm, p  =  0.001) respectively. No differences were observed for mean BP, CBFV or the ARI index. Use of FM or NC for measurement of EtCO 2 leads to physiological changes and differences in parameter values that need to be taken into consideration when interpreting and/or comparing results in studies of cerebral haemodynamics.

Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients.

PubMed

Balasubramanian, Padhmini; Boopathy, Vinoth; Govindasamy, Ezhumalai; Venkatesh, Basavaiya Prabhu

2016-08-01

Non-Alcoholic Fatty Liver Disease (NAFLD) has various spectrums of liver diseases like isolated fatty liver, steatohepatitis and cirrhosis usually progressing in a linear fashion. In this process they are known to cause certain haemodynamic changes in the portal flow and hepatic artery flow. The aim of the study was to study these haemodynamic changes in patients with NAFLD and to correlate it with the disease severity. Ninety patients diagnosed to have NAFLD based on ultrasound abdomen (30 each in grade1, grade2 and grade3 NAFLD) and 30 controls (Normal liver on ultrasound abdomen) were subjected to portal vein and hepatic artery Doppler study. Peak maximum velocity (Vmax), Peak minimum velocity (Vmin), Mean flow velocity (MFV), and Vein pulsality index (VPI) of the portal vein and hepatic artery resistivity index (HARI) of the hepatic artery were the doppler parameters which were assessed. Liver span was also assessed both for the fatty liver and controls. The mean Vmax, Vmin, MFV and VPI of the portal vein in patients with NAFLD was 12.23±1.74cm/sec, 9.31±1.45cm/sec, 10.76±1.48cm/sec, and 0.24±0.04 as compared to 14.05±2.43cm/sec, 10.01±2.27cm/sec, 12.23±2.47cm/sec, 0.3±0.08 in controls respectively. All these differences were statistically significant except for Vmin. The Mean HARI in patients with fatty liver was 0.65±0.06 when compared to controls of 0.75±0.06 (p=0.001). HARI (r-value of -0.517) had a better negative correlation followed by VPI (r-value of -0.44) and Vmax (r-value of -0.293) with the severity of NAFLD. MFV had a very weak negative correlation (r-value of -0.182) with the severity of NAFLD. The Vmax, MFV, VPI and HARI were significantly less when compared to controls suggesting a reduced portal flow and an increased hepatic arterial flow in patients with NAFLD. Among the parameters, HARI correlated better with the severity of NAFLD followed by VPI.

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

PubMed Central

Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-01-01

Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP –0.15 mmHg, SBP +1.44 mmHg, DBP −–0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). Conclusions I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol.

PubMed

Rönn, O; Bengtsson, B; Edgar, B; Raner, S

1985-01-01

In a single-blind randomised study in 9 healthy men we compared the acute haemodynamic effects of the calcium antagonists felodipine and verapamil, singly and in combination with metoprolol. Three different cumulative intravenous doses of 0.25, 0.75 and 1.5 mg felodipine and of 2.0, 4.0 and 8.0 mg verapamil or placebo were given as constant infusions over 5 minutes on 3 occasions and were followed by intravenous metoprolol (15 mg). Felodipine caused a significant and dose-dependent decrease in the total peripheral resistance, and an increase in the forearm blood flow by 8, 48 and 163% with progressively increasing doses showing that the drug is a potent arteriolar vasodilator. A significant and dose-dependent increase in heart rate and a decrease in the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio of up to 15% was also recorded, mainly reflecting a reflexogenic increase in the sympathetic tone. Total peripheral resistance, forearm blood flow, heart rate and the systolic time intervals were mainly unchanged after verapamil, whereas the PQ interval was prolonged. Metoprolol given after the 2 calcium antagonists caused a decrease in heart rate and blood flow and an increase in the total peripheral resistance and PEP/LVET ratio. The tolerability was good to all infusions.

Patient-Provider Communication and Health Outcomes Among Individuals With Atherosclerotic Cardiovascular Disease in the United States: Medical Expenditure Panel Survey 2010 to 2013.

PubMed

Okunrintemi, Victor; Spatz, Erica S; Di Capua, Paul; Salami, Joseph A; Valero-Elizondo, Javier; Warraich, Haider; Virani, Salim S; Blaha, Michael J; Blankstein, Ron; Butt, Adeel A; Borden, William B; Dharmarajan, Kumar; Ting, Henry; Krumholz, Harlan M; Nasir, Khurram

2017-04-01

Consumer-reported patient-provider communication (PPC) assessed by Consumer Assessment of Health Plans Survey in ambulatory settings is incorporated as a complementary value metric for patient-centered care of chronic conditions in pay-for-performance programs. In this study, we examine the relationship of PPC with select indicators of patient-centered care in a nationally representative US adult population with established atherosclerotic cardiovascular disease. The study population consisted of a nationally representative sample of 6810 individuals (aged ≥18 years), representing 18.3 million adults with established atherosclerotic cardiovascular disease (self-reported or International Classification of Diseases, Ninth Edition diagnosis) reporting a usual source of care in the 2010 to 2013 pooled Medical Expenditure Panel Survey cohort. Participants responded to questions from Consumer Assessment of Health Plans Survey that assessed PPC, and we developed a weighted PPC composite score using their responses, categorized as 1 (poor), 2 (average), and 3 (optimal). Outcomes of interest were (1) patient-reported outcomes: 12-item Short Form physical/mental health status, (2) quality of care measures: statin and ASA use, (3) healthcare resource utilization: emergency room visits and hospital stays, and (4) total annual and out-of-pocket healthcare expenditures. Atherosclerotic cardiovascular disease patients reporting poor versus optimal were over 2-fold more likely to report poor outcomes; 52% and 26% more likely to report that they are not on statin and aspirin, respectively, had a significantly greater utilization of health resources (odds ratio≥2 emergency room visit, 1.41 [95% confidence interval, 1.09-1.81]; odds ratio≥2 hospitalization, 1.36 [95% confidence interval, 1.04-1.79]), as well as an estimated $1243 ($127-$2359) higher annual healthcare expenditure. This study reveals a strong relationship between PPC and patient-reported outcomes, utilization of

Effects of Smad decoy ODN on shear stress-induced atherosclerotic ApoE-/-mouse

PubMed Central

An, Hyun-Jin; Lee, Woo-Ram; Kim, Kyung-Hyun; Kim, Jung-Yeon; Kim, Woon-Hae; Park, Kwan-Kyu; Youn, Sung Won

2015-01-01

Atherosclerosis is a complex disease which involves both genetic and environmental factors in its development and progression. Shear stress is the drag force per unit area acting on the endothelium as a result of blood flow, and it plays a critical role in plaque location and progression. TGF-β1 is often regarded to have pro-atherosclerotic effect on vascular disease. TGF-β1 downstream targets Smad, for regulating a set of genes associated with atherosclerosis. Therefore, modulation of TGF-β1 and Smad expression may be the important targets for the prevention and treatment of shear stress-induced vascular disease. However, the precise mechanism of the anti-atherosclerotic effects of novel therapeutic approach has not been elucidated by using animal models regarding the shear stress-induced vascular disease. Therefore, we designed to test whether Smad decoy ODN would prevent the development of atherosclerosis in the shear stress-induced ApoE-/-mice on a western diet. We examined the effect of cast placement on the development of atherosclerosis, and the carotid artery was harvested at the sacrifice to observe histological changes. Also, we evaluated the impact of Smad decoy ODN in the regulation of genes expression related to atherosclerosis, including TGF-β1, PAI-1, and α-SMA. Our results showed that western diet with cast placement developed atherosclerosis in ApoE-/-mouse. Also, administration of Smad decoy ODN decreases the expression of TGF-β1, PAI-1, and α-SMA. These results demonstrate the potential of Smad decoy ODN to prevent the progression of atherosclerosis in ApoE-/-mouse model with western diet and shear stress. PMID:26097583

Is triglyceride/HDL ratio a reliable screening test for assessment of atherosclerotic risk in patients with chronic inflammatory disease?

PubMed Central

Keles, Nursen; Aksu, Feyza; Aciksari, Gonul; Yilmaz, Yusuf; Demircioglu, Kenan; Kostek, Osman; Cekin, Muhammed Esad; Kalcik, Macit; Caliskan, Mustafa

2016-01-01

OBJECTIVE: The term chronic inflammatory disease (CID) refers to a category of inflammatory diseases that includes Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF). The incidence of adverse cardiovascular events is greater among patients with CID, though they may not have conventional atherosclerotic risk factors. Endothelial dysfunction is one of the underlying fundamental mechanisms that trigger development of atherosclerotic alterations in arteries, and flow-mediated dilatation (FMD) is a noninvasive method to determine endothelial dysfunction. Recent studies have shown a relationship between high triglyceride high-density lipoprotein cholesterol (TG/HDL-C) ratio and coronary atherosclerosis. Many studies have demonstrated that patients with CID have lower FMD values compared to healthy population, indicating endothelial dysfunction. However TG/HDL ratio and its relationship to FMD in patients with CID has not been investigated. The present study investigated whether TG/HDL ratio in CID patients differs from that of healthy population, and its relationship to FMD in patients with CID. METHODS: A total of 58 patients with CID and a group of 58 healthy volunteer individuals were enrolled in the study. FMD measurements were taken with high resolution ultrasound (US), and TG/HDL ratios were calculated. RESULTS: Patients with CID had significantly higher TG/HDL-C ratio (2.5 [2.2–2.8] vs 2.3 [2.1–2.5]; p=0.03) and lower FMD values (5.2 [4.2–6.3] vs 6.7 [6.3–9.7]; p<0.001), compared to healthy group, and a negative correlation was found between FMD levels and TG/HDL ratio of the study population. CONCLUSION: Higher TG/HDL ratio and lower FMD values found in CID patients may reflect increased atherosclerotic risk. PMID:28058384

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

PubMed

Elmaleh, D R; Fischman, A J; Tawakol, A; Zhu, A; Shoup, T M; Hoffmann, U; Brownell, A-L; Zamecnik, P C

2006-10-24

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

Balloon pulmonary angioplasty relieves haemodynamic stress towards untreated-side pulmonary vasculature and improves its resistance in patients with chronic thromboembolic pulmonary hypertension.

PubMed

Hosokawa, Kazuya; Abe, Kohtaro; Horimoto, Koshin; Yamasaki, Yuzo; Nagao, Michinobu; Tsutsui, Hiroyuki

2018-04-20

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by organised thrombotic obliteration of major vessels and small-vessel arteriopathy in the non-thrombosed vessels. The aim of this study was to investigate the impact of balloon pulmonary angioplasty (BPA) on the non-BPA-side pulmonary vasculature in patients with CTEPH. This study explored the outcomes of 20 unilateral BPA sessions in 13 CTEPH patients. We measured the pulmonary vascular resistance (PVR), pulmonary artery (PA) flow in the BPA-side and non-BPA-side lungs, respectively, using phase contrast MRI and cardiac catheterisation. The interval from BPA to the follow-up evaluation was 92.8±52.0 days. A single session of BPA decreased mean PA pressure from 37.4±6.2 to 30.9±6.5 mmHg (p<0.001). In the BPA side, BPA increased the PA flow from 1.58±0.65 to 1.95±0.62 L/min (p=0.001) and decreased the PVR from 27.3±27.4 to 14.4±9.0 Wood units (p=0.004). In contrast, it decreased both the non-BPA-side PA flow from 2.25±0.64 to 1.90±0.23 L/min (p=0.008) and the non-BPA-side PVR from 14.8±6.6 to 12.8±3.9 Wood units (p=0.01). BPA could relieve haemodynamic stress towards the non-BPA-side vasculature and decrease its PVR in patients with CTEPH, suggesting that it can suppress or regress the progression of the small-vessel arteriopathy in non-BPA-side vasculature, presumably due to haemodynamic unloading.

Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

PubMed

Mehta, Nehal N; Torigian, Drew A; Gelfand, Joel M; Saboury, Babak; Alavi, Abass

2012-05-02

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is

A computational evaluation of sedentary lifestyle effects on carotid hemodynamics and atherosclerotic events incidence.

PubMed

Caruso, Maria Vittoria; Serra, Raffaele; Perri, Paolo; Buffone, Gianluca; Caliò, Francesco Giuseppe; DE Franciscis, Stefano; Fragomeni, Fragomeni

2017-01-01

Hemodynamics has a key role in atheropathogenesis. Indeed, atherosclerotic phenomena occur in vessels characterized by complex geometry and flow pattern, like the carotid bifurcation. Moreover, lifestyle is a significant risk factor. The aim of this study is to evaluate the hemodynamic effects due to two sedentary lifestyles - sitting and standing positions - in the carotid bifurcation in order to identify the worst condition and to investigate the atherosclerosis incidence. The computational fluid dynamics (CFD) was chosen to carry out the analysis, in which in vivo non-invasive measurements were used as boundary conditions. Furthermore, to compare the two conditions, one patient-specific 3D model of a carotid bifurcation was reconstructed starting from computer tomography. Different mechanical indicators, correlated with atherosclerosis incidence, were calculated in addition to flow pattern and pressure distribution: the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and the relative residence time (RRT). The results showed that the bulb and the external carotid artery emergence are the most probable regions in which atherosclerotic events could happen. Indeed, low velocity and WSS values, high OSI and, as a consequence, areas with chaotic-swirling flow, with stasis (high RRT), occur. Moreover, the sitting position is the worst condition: considering a cardiac cycle, TAWSS is less than 17.2% and OSI and RRT are greater than 17.5% and 21.2%, respectively. This study suggests that if a person spends much time in the sitting position, a high risk of plaque formation and, consequently, of stenosis could happen.

The Veterans Affairs Cardiac Risk Score: Recalibrating the Atherosclerotic Cardiovascular Disease Score for Applied Use.

PubMed

Sussman, Jeremy B; Wiitala, Wyndy L; Zawistowski, Matthew; Hofer, Timothy P; Bentley, Douglas; Hayward, Rodney A

2017-09-01

Accurately estimating cardiovascular risk is fundamental to good decision-making in cardiovascular disease (CVD) prevention, but risk scores developed in one population often perform poorly in dissimilar populations. We sought to examine whether a large integrated health system can use their electronic health data to better predict individual patients' risk of developing CVD. We created a cohort using all patients ages 45-80 who used Department of Veterans Affairs (VA) ambulatory care services in 2006 with no history of CVD, heart failure, or loop diuretics. Our outcome variable was new-onset CVD in 2007-2011. We then developed a series of recalibrated scores, including a fully refit "VA Risk Score-CVD (VARS-CVD)." We tested the different scores using standard measures of prediction quality. For the 1,512,092 patients in the study, the Atherosclerotic cardiovascular disease risk score had similar discrimination as the VARS-CVD (c-statistic of 0.66 in men and 0.73 in women), but the Atherosclerotic cardiovascular disease model had poor calibration, predicting 63% more events than observed. Calibration was excellent in the fully recalibrated VARS-CVD tool, but simpler techniques tested proved less reliable. We found that local electronic health record data can be used to estimate CVD better than an established risk score based on research populations. Recalibration improved estimates dramatically, and the type of recalibration was important. Such tools can also easily be integrated into health system's electronic health record and can be more readily updated.

In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture.

PubMed

Huang, Yuan; Teng, Zhongzhao; Sadat, Umar; He, Jing; Graves, Martin J; Gillard, Jonathan H

2013-04-23

Atherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging. Twenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site. The predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R(2) = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03). Fatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.

Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia.

PubMed

Boord, Jeffrey B; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R; Fazio, Sergio; Linton, MacRae F; Hotamisligil, Gökhan S

2002-10-01

The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Mice deficient in aP2 and apolipoprotein E (aP2(-/-)apoE(-/-) mice) and apolipoprotein E-deficient control mice (apoE(-/-) mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE(-/-) control mice, male and female aP2(-/-)apoE(-/-) mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.

Precision phenotyping, panomics, and system-level bioinformatics to delineate complex biologies of atherosclerosis: rationale and design of the "Genetic Loci and the Burden of Atherosclerotic Lesions" study.

PubMed

Voros, Szilard; Maurovich-Horvat, Pal; Marvasty, Idean B; Bansal, Aruna T; Barnes, Michael R; Vazquez, Gustavo; Murray, Sarah S; Voros, Viktor; Merkely, Bela; Brown, Bradley O; Warnick, G Russell

2014-01-01

Complex biological networks of atherosclerosis are largely unknown. The main objective of the Genetic Loci and the Burden of Atherosclerotic Lesions study is to assemble comprehensive biological networks of atherosclerosis using advanced cardiovascular imaging for phenotyping, a panomic approach to identify underlying genomic, proteomic, metabolomic, and lipidomic underpinnings, analyzed by systems biology-driven bioinformatics. By design, this is a hypothesis-free unbiased discovery study collecting a large number of biologically related factors to examine biological associations between genomic, proteomic, metabolomic, lipidomic, and phenotypic factors of atherosclerosis. The Genetic Loci and the Burden of Atherosclerotic Lesions study (NCT01738828) is a prospective, multicenter, international observational study of atherosclerotic coronary artery disease. Approximately 7500 patients are enrolled and undergo non-contrast-enhanced coronary calcium scanning by CT for the detection and quantification of coronary artery calcium, as well as coronary artery CT angiography for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. In addition, patients undergo whole genome sequencing, DNA methylation, whole blood-based transcriptome sequencing, unbiased proteomics based on mass spectrometry, as well as metabolomics and lipidomics on a mass spectrometry platform. The study is analyzed in 3 subsequent phases, and each phase consists of a discovery cohort and an independent validation cohort. For the primary analysis, the primary phenotype will be the presence of any atherosclerotic plaque, as detected by cardiac CT. Additional phenotypic analyses will include per patient maximal luminal stenosis defined as 50% and 70% diameter stenosis. Single-omic and multi-omic associations will be examined for each phenotype; putative biomarkers will be assessed for association, calibration, discrimination, and reclassification. Copyright �

Immunochemical detection of food-derived polyphenols in the aorta: macrophages as a major target underlying the anti-atherosclerotic activity of polyphenols.

PubMed

Kawai, Yoshichika

2011-01-01

It has been suggested that polyphenol-rich diets decrease the risk of cardiovascular diseases. Although studies of the bioavailability of polyphenols, particularly their absorption and metabolism, have been reported recently, the tissue and cellular distributions underlying their biological mechanisms remain unknown. It is difficult to evaluate the specific localization of tissue and/or cellular polyphenols, because the method is limited to chromatography. To overcome these difficulties, we have developed anti-polyphenol antibodies to characterize immunohistochemically the localization of polyphenols and their metabolites in vivo. Two novel monoclonal antibodies were raised against quercetin and tea catechins, which represent flavonoid-type polyphenols distributed in foods and beverages, and are expected to exhibit anti-oxidative and anti-inflammatory activities in vivo. Using these antibodies, we identified activated macrophages as a specific target of these flavonoids during the development of atherosclerotic lesions. This review describes recent findings on the molecular actions of flavonoids that underly their anti-atherosclerotic activity in vivo.

Overexpression of hypoxia/inflammatory markers in atherosclerotic carotid plaques.

PubMed

Luque, Ana; Turu, Marta; Juan-Babot, Oriol; Cardona, Pere; Font, Angels; Carvajal, Ana; Slevin, Mark; Iborra, Elena; Rubio, Francisco; Badimon, Lina; Krupinski, Jerzy

2008-05-01

Hypoxia, angiogenesis and inflammation leads to plaque progression and remodelling and may significantly contribute towards plaque rupture and subsequent cerebrovascular events. Our aim was to study, markers of hypoxia and inflammation previously identified by microarray analysis, in atherosclerotic carotid arteries with low to moderate stenosis. We hoped to describe different cellular populations expressing the studied markers. The location of selected inflammatory molecules obtained as vascular transplants from organ donors were analysed by immunohistochemistry with monoclonal and polyclonal antibodies. Paraffin-embedded sections were cut and probed with antibodies recognizing active B and T-lymphocytes (CD30), hypoxia-inducible factor-1alpha, endoglin (CD105), Interleukin-6 and C-reactive protein. We observed a notable overexpression of HIF-1alpha in inflammatory and hypoxic areas of carotid arteries in all types of lesions from type II-V taken from the patients with carotid stenosis less than 50%. This suggests that HIF-1alpha may have a putative role in atherosclerosis progression and angiogenesis. Dynamic changes in the non-occluding plaques may explain some of the clinical events in patients with low to moderate carotid stenosis.

Progranulin expression in advanced human atherosclerotic plaque.

PubMed

Kojima, Yoji; Ono, Koh; Inoue, Katsumi; Takagi, Yasushi; Kikuta, Ken-ichiro; Nishimura, Masaki; Yoshida, Yoshinori; Nakashima, Yasuhiro; Matsumae, Hironobu; Furukawa, Yutaka; Mikuni, Nobuhiro; Nobuyoshi, Masakiyo; Kimura, Takeshi; Kita, Toru; Tanaka, Makoto

2009-09-01

Progranulin (PGRN) is a unique growth factor that plays an important role in cutaneous wound healing. It has an anti-inflammatory effect and promotes cell proliferation. However, when it is degraded to granulin peptides (GRNs) by neutrophil proteases, a pro-inflammatory reaction occurs. Since injury, inflammation and repair are common features in the progression of atherosclerosis, it is conceivable that PGRN plays a role in atherogenesis. Immunohistochemical analysis of human carotid endoatherectomy specimens indicated that vascular smooth muscle cells (vSMCs) in the intima expressed PGRN. Some macrophages in the plaque also expressed PGRN. We assessed the effect of PGRN on a human monocytic leukemia cell line (THP-1) and human aortic smooth muscle cells (HASMCs). PGRN alone had no effect on HASMC or THP-1 proliferation or migration. However, when THP-1 cells were stimulated with MCP-1, the number of migrated cells decreased in a PGRN-dose-dependent manner. TNF-alpha-induced HASMC migration was enhanced only at 10nM of PGRN. Interleukin-8 (IL-8) secretion from HASMCs was reduced by forced expression of PGRN and increased by RNAi-mediated knockdown of PGRN. While exogenous treatment with recombinant PGRN decreased IL-8 secretion, degraded recombinant GRNs increased IL-8 secretion from HASMCs. The expression of PGRN mainly reduces inflammation and its degradation into GRNs enhances inflammation in atherosclerotic plaque and may contribute to the progression of atherosclerosis.

Laser ablation of human atherosclerotic plaque without adjacent tissue injury

NASA Technical Reports Server (NTRS)

Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

1985-01-01

Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

The current management of carotid atherosclerotic disease: who, when and how?

PubMed Central

Ritter, Jens C.; Tyrrell, Mark R.

2013-01-01

Ischaemic stroke represents a major health hazard in the western world, which has a severe impact on society and the health-care system. Roughly, 10% of all first ischaemic strokes can be attributed to significant atherosclerotic disease of the carotid arteries. Correct management of these lesions is essential in the prevention and treatment of carotid disease-related ischaemic events. The close relationship between diagnosis and medical and surgical management makes it necessary that all involved physicians and surgeons have profound knowledge of management strategies beyond their specific speciality. Continuous improvement in pharmacological therapy and operative techniques as well as frequently changing guidelines represent a constant challenge for the individual health-care professional. This review gives a thorough outline of the up-to-date evidence-based management of carotid artery disease and discusses its current controversies. PMID:23197661

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

PubMed Central

Zhang, Mengyuan; He, Jianhua; Jiang, Cuiping; Zhang, Wenli; Yang, Yun; Wang, Zhiyu; Liu, Jianping

2017-01-01

Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core–shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium–macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic efficacies in model animals over other preparations. Thus, the HAase-responsive HDL-mimetic nanoparticle was shown in this study to be a promising nanocarrier for anti-atherogenic therapy, in the light of efficient iMΦ-targeted drug delivery and excellent function of

Cutting-Balloon Angioplasty Versus Balloon Angioplasty as Treatment for Short Atherosclerotic Lesions in the Superficial Femoral Artery: Randomized Controlled Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poncyljusz, Wojciech, E-mail: wponcyl@poczta.onet.pl; Falkowski, Aleksander, E-mail: bakhis@hot.pl; Safranow, Krzysztof, E-mail: chrissaf@mp.pl

2013-12-15

Purpose: To evaluate the treatments of a short-segment atherosclerotic stenosis in the superficial femoral arteries with the cutting balloon angioplasty (CBA) versus conventional balloon angioplasty [percutaneous transluminal angioplasty (PTA)] in a randomized controlled trial. Material and Methods: The study group comprised 60 patients (33 men, 27 women; average age 64 years) with a short ({<=}5 cm) focal SFA de novo atherosclerotic stenosis associated with a history of intermittent claudication or rest pain. The primary end point of this study was the rate of binary restenosis in the treated segment 12 months after the intervention. All patients were evenly randomized tomore » either the PTA or CBA treatment arms. Follow-up angiograms and ankle-brachial index (ABI) measurements were performed after 12 months. The evaluation of the restenosis rates and factors influencing its occurrence were calculated by logistic regression analysis. Results: In the intention-to-treat analysis, restenosis rates after 2-month follow-up were 9 of 30 (30 %) in the PTA group and 4 of 30 (13 %) in the CBA group (p = 0.117). In the actual treatment analysis, after exclusion of patients who required nitinol stent placement for a suboptimal result after angioplasty alone (5 patients in the PTA group and none in the CBA group), restenosis rates were 9 of 25 (36 %) and 4 of 30 (13 %), respectively (p = 0.049). In the intention-to-treat analysis there were also significant differences in ABI values between the PTA and CBA groups at 0.77 {+-} 0.11 versus 0.82 {+-} 0.12, respectively (p = 0.039), at 12 months. Conclusion: Based on the presented results of the trial, CBA seems to be a safer and more effective than PTA for treatment of short atherosclerotic lesions in the superior femoral artery.« less

Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

PubMed Central

Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

2016-01-01

Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Results: Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Conclusion: Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation. PMID:26687933

Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling.

PubMed

Vogel, Megan E; Idelman, Gila; Konaniah, Eddy S; Zucker, Stephen D

2017-04-01

Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice and elucidate the molecular processes underlying this effect. Bilirubin, at physiological concentrations (≤20 μmol/L), dose-dependently inhibits THP-1 monocyte migration across tumor necrosis factor α-activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross-linking of endothelial vascular cell adhesion molecule 1 (VCAM-1) or intercellular adhesion molecule 1 (ICAM-1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of VCAM-1 and ICAM-1 signaling. When administered to Ldlr -/- mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin-treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in VCAM-1 or ICAM-1 expression. Bilirubin suppresses atherosclerotic plaque formation in Ldlr -/- mice by disrupting endothelial VCAM-1- and ICAM-1-mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Effect of whole-body mild-cold exposure on arterial stiffness and central haemodynamics: a randomised, cross-over trial in healthy men and women.

PubMed

King, Sibella G; Ahuja, Kiran D K; Wass, Jezreel; Shing, Cecilia M; Adams, Murray J; Davies, Justin E; Sharman, James E; Williams, Andrew D

2013-05-01

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent predictors of cardiovascular risk and mortality, but little is known about the effect of air temperature changes on these variables. Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness (aortic and brachial PWV), and on central haemodynamics [including augmented pressure (AP), AIx], and aortic reservoir components [including reservoir and excess pressures (P ex)]. Sixteen healthy volunteers (10 men, age 43 ± 19 years; mean ± SD) were randomised to be studied under conditions of 12 °C (mild-cold) and 21 °C (control) on separate days. Supine resting measures were taken at baseline (ambient temperature) and after 10, 30, and 60 min exposure to each experimental condition in a climate chamber. There was no significant change in brachial blood pressure between mild-cold and control conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval (CI) 0.36-4.36; p = 0.01] and AIx (+6 %, 95 % CI 1.24-10.1; p = 0.02) increased, and time to maximum P ex (a component of reservoir function related to timing of peak aortic in-flow) decreased (-7 ms, 95 % CI -15.4 to 2.03; p = 0.01) compared to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI -0.47 to 0.55; p = 0.87) or brachial PWV (+0.36 m/s; -0.41 to 1.12; p = 0.35) between conditions. We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness.

SPH simulations of WBC adhesion to the endothelium: the role of haemodynamics and endothelial binding kinetics.

PubMed

Gholami, Babak; Comerford, Andrew; Ellero, Marco

2015-11-01

A multiscale Lagrangian particle solver introduced in our previous work is extended to model physiologically realistic near-wall cell dynamics. Three-dimensional simulation of particle trajectories is combined with realistic receptor-ligand adhesion behaviour to cover full cell interactions in the vicinity of the endothelium. The selected stochastic adhesion model, which is based on a Monte Carlo acceptance-rejection method, fits in our Lagrangian framework and does not compromise performance. Additionally, appropriate inflow/outflow boundary conditions are implemented for our SPH solver to enable realistic pulsatile flow simulation. The model is tested against in-vitro data from a 3D geometry with a stenosis and sudden expansion. In both steady and pulsatile flow conditions, results show close agreement with the experimental ones. Furthermore we demonstrate, in agreement with experimental observations, that haemodynamics alone does not account for adhesion of white blood cells, in this case U937 monocytic human cells. Our findings suggest that the current framework is fully capable of modelling cell dynamics in large arteries in a realistic and efficient manner.

Profilin-1 Is Expressed in Human Atherosclerotic Plaques and Induces Atherogenic Effects on Vascular Smooth Muscle Cells

PubMed Central

Caglayan, Evren; Romeo, Giulio R.; Kappert, Kai; Odenthal, Margarete; Südkamp, Michael; Body, Simon C.; Shernan, Stanton K.; Hackbusch, Daniel; Vantler, Marius; Kazlauskas, Andrius; Rosenkranz, Stephan

2010-01-01

Background Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo. Methodology Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans. Principal Findings In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10−6 M) in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70S6 kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, LY294002) or Src-family kinases (SU6656, PP2), but not PLCγ (U73122), completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group). Conclusions Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall

Atherosclerotic plaque in the left carotid artery is more vulnerable than in the right.

PubMed

Selwaness, Mariana; van den Bouwhuijsen, Quirijn; van Onkelen, Robbert S; Hofman, Albert; Franco, Oscar H; van der Lugt, Aad; Wentzel, Jolanda J; Vernooij, Meike

2014-11-01

Ischemic stroke is more often diagnosed in the left hemisphere than in the right. It is unknown whether this asymmetrical prevalence relates to differences in carotid atherosclerosis. We compared atherosclerotic plaque prevalence, severity, and composition between left and right carotid arteries. In a population-based cohort, carotid MRI scanning was performed in 1414 stroke-free participants (≥45 years). Using a multisequence MRI protocol, we assessed the prevalence, stenosis, and thickness of the plaque and its predominant component (ie, lipid core, intraplaque hemorrhage, calcification, or fibrous tissue in each carotid artery). Differences between left and right side were tested using paired t tests, McNemar test and Generalized Estimating Equation analyses. The majority (85%) of the participants had bilateral carotid plaques. Unilateral plaques were twice more prevalent on the left than on the right side (67% versus 33%; P<0.001). Plaque thickness was also greater on the left (3.1±1.2 versus 2.9±1.3 mm; P<0.001); degree of stenosis did not differ. Intraplaque hemorrhage and fibrous tissue were more prevalent on the left (9.1 versus 5.9%; P<0.001 and 45.0 versus 38.5%; P<0.001), whereas calcification occurred more often on the right (37.4 versus 31.6% at the left; P<0.001). Lipid was equally distributed. Carotid atherosclerotic plaque size and composition are not symmetrically distributed. Predominance of intraplaque hemorrhage in left-sided carotid plaques suggests a greater vulnerability as opposed to right-sided plaques, which are more calcified and therefore considered more stable. © 2014 American Heart Association, Inc.

Vulnerable atherosclerotic plaque morphology in apolipoprotein E-deficient mice unable to make ascorbic Acid.

PubMed

Nakata, Yukiko; Maeda, Nobuyo

2002-03-26

Oxidative stress is thought to play an important role in atherogenesis, suggesting that antioxidants could prevent coronary artery disease. However, the efficacy of vitamin C in reducing atherosclerosis is debatable in humans and has not been tested rigorously in animals. Gulo(-/-)Apoe(-/-) mice were used to test a hypothesis that chronic vitamin C deficiency enhances the initiation and development of atherosclerosis. These mice are dependent on dietary vitamin C because of the lack of L-gulonolactone-gamma-oxidase and are prone to develop atherosclerosis because of lacking apolipoprotein E. Beginning at 6 weeks of age, the Gulo(-/-)Apoe(-/-) mice were fed regular chow or Western-type diets containing high fat and supplemented with either 0.033 g or 3.3 g/L of vitamin C in their drinking water. This regimen produced mice with chronically low vitamin C (average 1.5 microg/mL in plasma) or high vitamin C (average 10 to 30 microg/mL in plasma). Morphometric analysis showed that within each sex, age, and diet group, the sizes of the atherosclerotic plaques were not different between low vitamin C mice and high vitamin C mice. However, advanced plaques in the low vitamin C mice had significantly reduced amounts of Sirius red-staining collagen (36.4+/-2.2% versus 54.8+/-2.3%, P<0.0001), larger necrotic cores within the plaques, and reduced fibroproliferation and neovascularization in the aortic adventitia. Chronic vitamin C deficiency does not influence the initiation or progression of atherosclerotic plaques but severely compromises collagen deposition and induces a type of plaque morphology that is potentially vulnerable to rupture.

Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino-acid-derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions and advanced atherosclerotic lesions.

PubMed Central

Hazen, S L; Gaut, J P; Crowley, J R; Hsu, F F; Heinecke, J W

2000-01-01

Reactive aldehydes might have a pivotal role in the pathogenesis of atherosclerosis by covalently modifying low-density lipoprotein (LDL). However, the identities of the aldehyde adducts that form on LDL in vivo are not yet clearly established. We previously demonstrated that the haem protein myeloperoxidase oxidizes proteins in the human artery wall. We also have shown that p-hydroxyphenylacetaldehyde (pHA), the aldehyde that forms when myeloperoxidase oxidizes L-tyrosine, covalently modifies the N(epsilon)-lysine residues of proteins. The resulting Schiff base can be quantified as N(epsilon)-[2-(p-hydroxyphenyl)ethyl]lysine (pHA-lysine) after reduction with NaCNBH(3). Here we demonstrate that pHA-lysine is a marker for LDL that has been modified by myeloperoxidase, and that water-soluble, but not lipid-soluble, antioxidants inhibit the modification of LDL protein. To determine whether myeloperoxidase-generated aldehydes might modify LDL in vivo, we used a combination of isotope-dilution GC-MS to quantify pHA-lysine in aortic tissues at various stages of lesion evolution. We also analysed LDL isolated from atherosclerotic aortic tissue. Comparison of normal and atherosclerotic aortic tissue demonstrated a significant elevation (more than 10-fold) of the reduced Schiff base adduct in fatty streaks, intermediate lesions and advanced lesions compared with normal aortic tissue. Moreover, the level of pHA-lysine in LDL recovered from atherosclerotic aortic intima was 200-fold that in plasma LDL of healthy donors. These results indicate that pHA-lysine, a specific covalent modification of LDL, is generated in human atherosclerotic vascular tissue. They also raise the possibility that reactive aldehydes generated by myeloperoxidase have a role in converting LDL into an atherogenic lipoprotein. PMID:11104675

[Management of atherosclerotic renal-artery stenosis in 2016].

PubMed

Fournier, Thomas; Sens, Florence; Rouvière, Olivier; Millon, Antoine; Juillard, Laurent

2017-02-01

Endovascular revascularization as treatment of atherosclerotic renal-artery stenosis (aRAS) is controversial since 3 large and multicentric randomised trials (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous transluminal renal-artery stenting (PTRAS) over medical treatment only (MT). However, considering the multiple bias of these trials, among which questionable inclusion criterias, these results must be extrapolated in clinical practice with caution. New pathophysiological data have been helping to understand why restoring blood flow does not necessarily lead to kidney function improvement. Today, the diagnostic approach must in one hand confirm the artery stenosis and on the other hand assess its severity and impact on the kidney. Therapeutic options still lie on the American guidelines published in 2006, since no study data can be reasonably used in everyday practice. However, particular sub-groups of patients who could benefit from revascularisation have been identified through recent cohort studies. Further prospective studies are needed in order to confirm the superiority of PTRAS in these populations. Meanwhile, multidisciplinary approach should be promoted, in order to provide the best treatment for each patient. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Primary Prevention of Atherosclerotic Cardiovascular Disease in Women

PubMed Central

McKibben, Rebeccah A.; Al Rifai, Mahmoud; Mathews, Lena M.; Michos, Erin D.

2016-01-01

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women. PMID:28149430

[Adrenal hormones in the formation of atherosclerotic precursors in adolescents with primary arterial hypertension].

PubMed

Bogmat, L F

1993-01-01

The components of blood lipid spectrum (total cholesterol, triglycerides and high density lipoprotein cholesterol) were studied in 131 adolescents (12-18 years old) with primary arterial hypertension at various levels of adrenal hormones (hydrocortisone and aldosterone) and blood plasma renin activity. The optimal ratio of lipid components in blood was detected if concentrations of adrenal hormones and blood plasma renin activity were low. Hyperfunction of the adrenal cortex in teen-agers contributed both to the development of hypertension and to atherosclerotic changes in vessels. This suggests that definite forms of hypertension occurred in adults, with specific impairments in the metabolism of blood serum lipids, were developed during the juvenile age.

An integrated method for atherosclerotic carotid plaque segmentation in ultrasound image.

PubMed

Qian, Chunjun; Yang, Xiaoping

2018-01-01

Carotid artery atherosclerosis is an important cause of stroke. Ultrasound imaging has been widely used in the diagnosis of atherosclerosis. Therefore, segmenting atherosclerotic carotid plaque in ultrasound image is an important task. Accurate plaque segmentation is helpful for the measurement of carotid plaque burden. In this paper, we propose and evaluate a novel learning-based integrated framework for plaque segmentation. In our study, four different classification algorithms, along with the auto-context iterative algorithm, were employed to effectively integrate features from ultrasound images and later also the iteratively estimated and refined probability maps together for pixel-wise classification. The four classification algorithms were support vector machine with linear kernel, support vector machine with radial basis function kernel, AdaBoost and random forest. The plaque segmentation was implemented in the generated probability map. The performance of the four different learning-based plaque segmentation methods was tested on 29 B-mode ultrasound images. The evaluation indices for our proposed methods were consisted of sensitivity, specificity, Dice similarity coefficient, overlap index, error of area, absolute error of area, point-to-point distance, and Hausdorff point-to-point distance, along with the area under the ROC curve. The segmentation method integrated the random forest and an auto-context model obtained the best results (sensitivity 80.4 ± 8.4%, specificity 96.5 ± 2.0%, Dice similarity coefficient 81.0 ± 4.1%, overlap index 68.3 ± 5.8%, error of area -1.02 ± 18.3%, absolute error of area 14.7 ± 10.9%, point-to-point distance 0.34 ± 0.10 mm, Hausdorff point-to-point distance 1.75 ± 1.02 mm, and area under the ROC curve 0.897), which were almost the best, compared with that from the existed methods. Our proposed learning-based integrated framework investigated in this study could be useful for

Cholesterol and prevention of atherosclerotic events: limits of a new frontier.

PubMed

Macedo, Luís Eduardo Teixeira de; E, Faerstein

2017-01-12

Control of atherosclerotic cardiovascular disease - a highly prevalent condition and one of the main causes of mortality in Brazil and worldwide - is a recurrent subject of great interest for public health. Recently, three new guidelines on dyslipidemia and atherosclerosis prevention have been published. The close release of these important publications is a good opportunity for comparison: the Brazilian model has greater sensitivity, the English model does not work with risk stratification, and the American model may be overestimating the risk. This will allow reflection on current progress and identification of controversial aspects which still require further research and debate. It is also an opportunity to discuss issues related to early diagnosis and its efficiency as a preventive strategy for atherosclerotic disease: the transformation of risk into disease, the gradual reduction of cut-off points, the limitations of the screening strategy, and the problem of overdiagnosis. RESUMO O controle da doença cardiovascular aterosclerótica - morbidade de alta prevalência e uma das principais causas de mortalidade no Brasil e no mundo - continua sendo tema de grande interesse para a Saúde Pública. Recentemente, três novas diretrizes sobre dislipidemia e prevenção da aterosclerose foram divulgadas. A convergência no tempo dessas importantes publicações constitui boa oportunidade para sua comparação: o modelo brasileiro tem maior sensibilidade, o inglês não trabalha com risco estratificado e o norte-americano parece estar superestimando o risco.Isso permitirá reflexões acerca dos avanços que já foram alcançados e identificação de aspectos ainda controversos, que seguem exigindo novas pesquisas e debates. É também uma oportunidade para discutir questões relacionadas ao diagnóstico precoce e sua eficiência como estratégia preventiva da doença aterosclerótica: as transformações do risco em doença, a diminuição progressiva de pontos de

Inhalation exposure of gas-metal arc stainless steel welding fume increased atherosclerotic lesions in apolipoprotein E knockout mice.

PubMed

Erdely, Aaron; Hulderman, Tracy; Salmen-Muniz, Rebecca; Liston, Angie; Zeidler-Erdely, Patti C; Chen, Bean T; Stone, Samuel; Frazer, David G; Antonini, James M; Simeonova, Petia P

2011-07-04

Epidemiological studies suggest that welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) welding fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest welding may result in adverse cardiovascular effects. Published by Elsevier Ireland Ltd.

Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

PubMed

Glover, LaShaunta M; Bass, Martha Ann; Carithers, Teresa; Loprinzi, Paul D

2016-04-01

There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks. Copyright © 2016 Elsevier Inc. All rights reserved.

Adipocyte Fatty Acid–Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia

PubMed Central

Boord, Jeffrey B.; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R.; Fazio, Sergio; Linton, MacRae F.; Hotamisligil, Gökhan S.

2014-01-01

Objective The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Methods and Results Mice deficient in aP2 and apolipoprotein E (aP2−/−apoE−/− mice) and apolipoprotein E-deficient control mice (apoE−/− mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE−/− control mice, male and female aP2−/−apoE−/− mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. Conclusions These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis. PMID:12377750

Use of Low-dose Aspirin as Secondary Prevention of Atherosclerotic Cardiovascular Disease Among US Adults (From the National Health Interview Survey, 2012)

PubMed Central

Fang, Jing; George, Mary G.; Gindi, Renee M.; Hong, Yuling; Yang, Quanhe; Ayala, Carma; Ward, Brian W.; Loustalot, Fleetwood

2015-01-01

Current guidelines recommend that adults with atherosclerotic cardiovascular disease take low-dose aspirin or other antiplatelet medications as secondary prevention of recurrent cardiovascular events. Yet, no national level assessment of low-dose aspirin use for secondary prevention of cardiovascular disease has been reported among a community-based population. Using data from the 2012 National Health Interview Survey, we assessed low-dose aspirin use among those with atherosclerotic cardiovascular disease. We estimated the prevalence ratios of low-dose aspirin use, adjusting for sociodemographic status, health insurance, and cardiovascular risk factors. Among those with atherosclerotic cardiovascular disease (n=3,068), 76% had been instructed to take aspirin, and 88% of those were following this advice. Of those not advised, 11% took aspirin on this own. Overall, 70% were taking aspirin (including those who followed their health care provider's advice and those who were not advised but took aspirin on their own). Logistic regression models showed that women, non-Hispanic blacks and Hispanics, those aged 40–64 years, with a high school education or with some college, or with fewer cardiovascular disease risk factors were less likely to take aspirin than men, non-Hispanic whites, those aged ≥65 years, with a college education or higher, or with all four selected cardiovascular disease risk factors, respectively. Additional analyses conducted among those with coronary heart disease only (n=2,007) showed similar patterns. In conclusion, use of low-dose aspirin for secondary prevention was 70%, with high reported adherence to health care providers' advice to take low-dose aspirin (88%), and significant variability within subgroups. PMID:25670639

The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques.

PubMed

Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H

2015-11-05

Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. Copyright © 2015 The Authors. Published by

PGE2-EP2 signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-κB

PubMed Central

Aoki, T; Nishimura, M; Matsuoka, T; Yamamoto, K; Furuyashiki, T; Kataoka, H; Kitaoka, S; Ishibashi, R; Ishibazawa, A; Miyamoto, S; Morishita, R; Ando, J; Hashimoto, N; Nozaki, K; Narumiya, S

2011-01-01

BACKGROUND AND PURPOSE Cerebral aneurysm is a frequent cerebrovascular event and a major cause of fatal subarachnoid haemorrhage, but there is no medical treatment for this condition. Haemodynamic stress and, recently, chronic inflammation have been proposed as major causes of cerebral aneurysm. Nevertheless, links between haemodynamic stress and chronic inflammation remain ill-defined, and to clarify such links, we evaluated the effects of prostaglandin E2 (PGE2), a mediator of inflammation, on the formation of cerebral aneurysms. EXPERIMENTAL APPROACH Expression of COX and prostaglandin E synthase (PGES) and PGE receptors were examined in human and rodent cerebral aneurysm. The incidence, size and inflammation of cerebral aneurysms were evaluated in rats treated with COX-2 inhibitors and mice lacking each prostaglandin receptor. Effects of shear stress and PGE receptor signalling on expression of pro-inflammatory molecules were studied in primary cultures of human endothelial cells (ECs). KEY RESULTS COX-2, microsomal PGES-1 and prostaglandin E receptor 2 (EP2) were induced in ECs in the walls of cerebral aneurysms. Shear stress applied to primary ECs induced COX-2 and EP2. Inhibition or loss of COX-2 or EP2in vivo attenuated each other's expression, suppressed nuclear factor κB (NF-κB)-mediated chronic inflammation and reduced incidence of cerebral aneurysm. EP2 stimulation in primary ECs induced NF-κB activation and expression of the chemokine (C-C motif) ligand 2, essential for cerebral aneurysm. CONCLUSIONS AND IMPLICATIONS These results suggest that shear stress activated PGE2-EP2 pathway in ECs and amplified chronic inflammation via NF-κB. We propose EP2 as a therapeutic target in cerebral aneurysm. PMID:21426319

Mid-term haemodynamic and clinical results after aortic valve replacement using the Freedom Solo stentless bioprosthesis versus the Carpentier Edwards Perimount stented bioprosthesis.

PubMed

van der Straaten, Ellen P J; Rademakers, Leonard M; van Straten, Albert H M; Houterman, Saskia; Tan, M Erwin S H; Soliman Hamad, Mohamed A

2016-04-01

The aim of this study was to investigate the mid-term haemodynamic and clinical results after aortic valve replacement (AVR) using the Sorin Freedom Solo (SFS) stentless bioprosthesis, compared with the standard Carpentier Edwards Perimount (CEP) stented bioprosthesis. In this retrospective cohort study of prospectively collected data, 116 patients were included in the SFS group (53 males; median age 74 years, range 56-85 years), and 122 patients in the CEP group (85 males; median age 73 years, range 43-88 years) between July 2007 and January 2013. Echocardiography was performed at 6 weeks after surgery in our centre, and the most recent echocardiography (in our centre or in referring cardiology departments) was requested. Between September 2013 and April 2014, all patients were called by the same researcher to gain clinical follow-up data. Mid-term mortality was 16.4% in the SFS group (19 patients) and 21.3% in the CEP group (26 patients); (P = 0.3). The mean transvalvular gradient was 7.4 ± 3.1 mmHg in the SFS group, and 11.6 ± 3.2 mmHg in the CEP group at 6 weeks postoperatively (P < 0.001). When stratified by labelled valve size, mean gradients were significantly lower in the SFS group for every size (P ≤ 0.03). After 3.3 ± 1.4 years of follow-up, the mean gradient was still significantly lower in the SFS group than that in the CEP group (P < 0.001). Clinical follow-up showed relatively low complication rates. These data suggest that the Sorin Freedom Solo stentless bioprosthesis is as safe as the Carpentier Edwards bioprosthesis, and provides better short- and mid-term haemodynamic performance than the Carpentier Edwards bioprosthesis. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase in Sclerostin Levels

PubMed Central

Morales-Santana, Sonia; García-Fontana, Beatriz; García-Martín, Antonia; Rozas-Moreno, Pedro; García-Salcedo, José Antonio; Reyes-García, Rebeca; Muñoz-Torres, Manuel

2013-01-01

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients. PMID:23288857

[Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke].

PubMed

Li, Ying; Wang, Pei; Chai, Mei-Jing; Yang, Fan; Li, Hong-Shan; Zhao, Jing; Wang, Huan; Lu, Dan-Dan

2016-11-01

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in

Measurement of drug and macromolecule diffusion across atherosclerotic rabbit aorta ex vivo by attenuated total reflection-Fourier transform infrared imaging

NASA Astrophysics Data System (ADS)

Palombo, Francesca; Danoux, Charlène B.; Weinberg, Peter D.; Kazarian, Sergei G.

2009-07-01

Diffusion of two model drugs-benzyl nicotinate and ibuprofen-and the plasma macromolecule albumin across atherosclerotic rabbit aorta was studied ex vivo by attenuated total reflection-Fourier transform infrared (ATR-FTIR) imaging. Solutions of these molecules were applied to the endothelial surface of histological sections of the aortic wall that were sandwiched between two impermeable surfaces. An array of spectra, each corresponding to a specific location in the section, was obtained at various times during solute diffusion into the wall and revealed the distribution of the solutes within the tissue. Benzyl nicotinate in Ringer's solution showed higher affinity for atherosclerotic plaque than for apparently healthy tissue. Transmural concentration profiles for albumin demonstrated its permeation across the section and were consistent with a relatively low distribution volume for the macromolecule in the middle of the wall. The ability of albumin to act as a drug carrier for ibuprofen, otherwise undetected within the tissue, was demonstrated by multivariate subtraction image analysis. In conclusion, ATR-FTIR imaging can be used to study transport processes in tissue samples with high spatial and temporal resolution and without the need to label the solutes under study.

Effect of Fontan geometry on exercise haemodynamics and its potential implications.

PubMed

Tang, Elaine; Wei, Zhenglun Alan; Whitehead, Kevin K; Khiabani, Reza H; Restrepo, Maria; Mirabella, Lucia; Bethel, James; Paridon, Stephen M; Marino, Bradley S; Fogel, Mark A; Yoganathan, Ajit P

2017-11-01

Exercise intolerance afflicts Fontan patients with total cavopulmonary connections (TCPCs) causing a reduction in quality of life. Optimising TCPC design is hypothesised to have a beneficial effect on exercise capacity. This study investigates relationships between TCPC geometries and exercise haemodynamics and performance. This study included 47 patients who completed metabolic exercise stress test with cardiac magnetic resonance (CMR). Phase-contrast CMR images were acquired immediately following supine lower limb exercise. Both anatomies and exercise vessel flow rates at ventilatory anaerobic threshold (VAT) were extracted. The vascular modelling toolkits were used to analyse TCPC geometries. Computational simulations were performed to quantify TCPC indexed power loss (iPL) at VAT. A highly significant inverse correlation was found between the TCPC diameter index, which factors in the narrowing of TCPC vessels, with iPL at VAT (r=-0.723, p<0.001) but positive correlations with exercise performance variables, including minute oxygen consumption (VO 2 ) at VAT (r=0.373, p=0.01), VO 2 at peak exercise (r=0.485, p=0.001) and work at VAT/weight (r=0.368, p=0.01). iPL at VAT was negatively correlated with VO 2 at VAT (r=-0.337, p=0.02), VO 2 at peak exercise (r=-0.394, p=0.007) and work at VAT/weight (r=-0.208, p=0.17). Eliminating vessel narrowing in TCPCs and reducing elevated iPL at VAT could enhance exercise tolerance for patients with TCPCs. These findings could help plan surgical or catheter-based strategies to improve patients' exercise capacity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Haemodynamic responses to dehydration in the resting and exercising human leg.

PubMed

Pearson, James; Kalsi, Kameljit K; Stöhr, Eric J; Low, David A; Barker, Horace; Ali, Leena; González-Alonso, José

2013-06-01

Dehydration and hyperthermia reduces leg blood flow (LBF), cardiac output ([Formula: see text]) and arterial pressure during whole-body exercise. It is unknown whether the reductions in blood flow are associated with dehydration-induced alterations in arterial blood oxygen content (C aO2) and O2-dependent signalling. This study investigated the impact of dehydration and concomitant alterations in C aO2 upon LBF and [Formula: see text]. Haemodynamics, arterial and femoral venous blood parameters and plasma [ATP] were measured at rest and during one-legged knee-extensor exercise in 7 males in four conditions: (1) control, (2) mild dehydration, (3) moderate dehydration, and (4) rehydration. Relative to control, C aO2 and LBF increased with dehydration at rest and during exercise (C aO2: from 199 ± 1 to 208 ± 2, and 202 ± 2 to 210 ± 2 ml L(-1) and LBF: from 0.38 ± 0.04 to 0.77 ± 0.09, and 1.64 ± 0.09 to 1.88 ± 0.1 L min(-1), respectively). Similarly, [Formula: see text] was unchanged or increased with dehydration at rest and during exercise, whereas arterial and leg perfusion pressures declined. Following rehydration, C aO2 declined (to 193 ± 2 mL L(-1)) but LBF remained elevated. Alterations in LBF were unrelated to C aO2 (r (2) = 0.13-0.27, P = 0.48-0.64) and plasma [ATP]. These findings suggest dehydration and concomitant alterations in C aO2 do not compromise LBF despite reductions in plasma [ATP]. While an additive or synergistic effect cannot be excluded, reductions in LBF during exercise with dehydration may not necessarily be associated with alterations in C aO2 and/or intravascular [ATP].

The influence of water ingestion on postexercise hypotension and standing haemodynamics.

PubMed

Mendonca, Goncalo V; Fernhall, Bo

2016-11-01

In young healthy adults, postexercise hypotension (PEH) occurs after a single bout of dynamic exercise due to peripheral vasodilation. Gravitational stress may further aggravate the magnitude of PEH, thus predisposing to orthostatic intolerance. As water drinking activates sympathetic vasoconstriction, it might offset PEH via enhanced α-adrenergic vascular responsiveness. We hypothesized that water ingestion before exercise would decrease the magnitude of PEH and improve the haemodynamic reaction to active standing postmaximal exercise. In a randomized fashion, 17 healthy adults (nine men; eight women, 21·2 ± 1·6 years) ingested 50 and 500 ml of water before completing resting, cycle ergometer and recovery protocols on two separate days. After exercise, measurements [arterial blood pressure (BP), heart rate and spectral heart rate variability (HRV)] were taken in the seated position followed by 5 min of active standing. Compared to that seen post-50 ml of water, the 500 ml volume elicited an overall increase in BP (P < 0·05). Nevertheless, the magnitude of PEH was not different after either volume of water. There was an overall bradycardic effect of water, and this was accompanied by increased high-frequency power (P < 0·05). Finally, no BP, heart rate or HRV differences were found between conditions in response to active standing. These data suggest that, despite being well preserved after maximal exercise, the water pressor response does not affect the magnitude of PEH. They also indicate that drinking 500 ml of water does not impact the BP, heart rate or HRV response to 5 min of active standing during recovery postmaximal exercise. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Survival of Atherosclerotic Calcifications in Skeletonized Material: Forensic and Pathological Implications.

PubMed

Biehler-Gomez, Lucie; Cappella, Annalisa; Castoldi, Elisa; Martrille, Laurent; Cattaneo, Cristina

2018-03-01

Atherosclerosis is a chronic inflammatory disease creating calcifying plaques in the arterial walls. Because its paleopathological diagnosis remains little studied on skeletal remains, its impact on forensic and archeological data is completely underestimated. Here, 24 skeletal remains from the Milano Cemetery Skeletal Collection have been studied to evaluate the chance of atherosclerotic calcification survival, retrieval, and identification. Through direct comparison with a known autopsy collection and literature, the identification and categorization of several types of calcifications were performed. Clothing elements such as tights or socks played a definitive role in the preservation of the calcifications; hence they are more likely to be found in forensic cases than in archeological ones. Therefore, vascular calcifications are possible to collect and identify in skeletal remains if sufficient care is given to their recovery. Consequently and as markers of the disease, such identification can provide valuable pathological information for forensic and archeological cases. © 2017 American Academy of Forensic Sciences.

Vertebral artery ostium atherosclerotic plaque as a potential source of posterior circulation ischemic stroke: result from borgess medical center vertebral artery ostium stenting registry.

PubMed

Al-Ali, Firas; Barrow, Tom; Duan, Li; Jefferson, Anne; Louis, Susan; Luke, Kim; Major, Kevin; Smoker, Sandy; Walker, Sarah; Yacobozzi, Margaret

2011-09-01

Although atherosclerotic plaque in the carotid and coronary arteries is accepted as a cause of ischemia, vertebral artery ostium (VAO) atherosclerotic plaque is not widely recognized as a source of ischemic stroke. We seek to demonstrate its implication in some posterior circulation ischemia. This is a nonrandomized, prospective, single-center registry on consecutive patients presenting with posterior circulation ischemia who underwent VAO stenting for significant atherosclerotic stenosis. Diagnostic evaluation and imaging studies determined the likelihood of this lesion as the symptom source (highly likely, probable, or highly unlikely). Patients were divided into 4 groups in decreasing order of severity of clinical presentation (ischemic stroke, TIA then stroke, TIA, asymptomatic), which were compared with the morphological and hemodynamic characteristics of the VAO plaque. Clinical follow-up 1 year after stenting assessed symptom recurrence. One hundred fourteen patients underwent stenting of 127 lesions; 35% of the lesions were highly likely the source of symptoms, 53% were probable, and 12% were highly unlikely. Clinical presentation correlated directly with plaque irregularity and presence of clot at the VAO, as did bilateral lesions and presence of tandem lesions. Symptom recurrence at 1 year was 2%. Thirty-five percent of the lesions were highly likely the source of the symptoms. A direct relationship between some morphological/hemodynamic characteristics and the severity of clinical presentation was also found. Finally, patients had a very low rate of symptom recurrence after treatment. These 3 observations point strongly to VAO plaque as a potential source of some posterior circulation stroke.

Decreased expression of liver X receptor-α in macrophages infected with Chlamydia pneumoniae in human atherosclerotic arteries in situ.

PubMed

Bobryshev, Yuri V; Orekhov, Alexander N; Killingsworth, Murray C; Lu, Jinhua

2011-01-01

In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells. Copyright © 2011 S. Karger AG, Basel.

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with amore » high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.« less

Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics.

PubMed

Abraham, William T; Raynolds, Mary V; Badesch, David B; Wynne, Kristine M; Groves, Bertron M; Roden, Robert L; Robertson, Alastair D; Lowes, Brian D; Zisman, Lawrence S; Voelkel, Norbert F; Bristow, Michael R; Perryman, M Benjamin

2003-03-01

HYPOTHESIS/INTRODUCTION: A polymorphic marker within the angiotensin- converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in population-based healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29+0.27 vs. 5.07+0.37 L/minute, p=0.002) and the mean right atrial pressure tended to be higher (8.85+1.29 vs. 4.92+1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14+0.12 vs. 2.40+0.28, p=0.02). 1) The ACE DD

Recanalization Results After Intracranial Stenting of Atherosclerotic Stenoses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blasel, Stella, E-mail: Stella.Blasel@kgu.de; Yuekzek, Zeynep; Kurre, Wiebke

2010-10-15

The purpose of this investigation was to provide a detailed description of the angiographic results after stenting of high-grade intracranial stenosis using balloon-expandable stents. Forty consecutive patients with symptomatic atherosclerotic intracranial stenosis >50% received endovascular treatment by placement of balloon-expandable stents using the concept of slight underdilation and strict avoidance of overdilation. Intra-arterial digital subtraction angiography images before and after stenting in the same projection were reviewed for pre- and post-therapeutic measurement of the degree of stenosis and evaluation of morphologic criteria like plaque coverage, stent apposition, patency of side branches, and signs of dissection or vasospasm. Stenting decreased themore » mean percentage stenosis from 76.2 (WASID criteria) to 20.8%. Residual stenosis ranged from 0 to 55% with residual stenosis >50% in two of 40 cases. Technical success rate was 95%. There were no major vessel complications, but minor abnormalities like incomplete stent apposition (8/40) or plaque coverage (7/40), incomplete filling of side branches (13/40), and minor dissections after stenting (2/40) were seen. One case with incomplete stent apposition and two cases with side branch compromise were associated with clinical symptoms. In conclusion, intracranial stenting with slight underdilation avoided major vessel complication and created reliable luminal gain. Suboptimal recanalization results were frequently detected and may be the source of neurological complications in individual cases.« less

Elevated lipoprotein(a) levels are associated with coronary artery calcium scores in asymptomatic individuals with a family history of premature atherosclerotic cardiovascular disease.

PubMed

Verweij, Simone L; de Ronde, Maurice W J; Verbeek, Rutger; Boekholdt, S Matthijs; Planken, R Nils; Stroes, Erik S G; Pinto-Sietsma, Sara-Joan

2018-02-16

Elevated lipoprotein(a) (Lp(a)) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Individuals with a family history of premature ASCVD are at increased cardiovascular risk with concomitantly a higher burden of (subclinical) atherosclerosis. However, whether Lp(a) contributes to the increased atherosclerotic burden in these individuals remains to be established. In this study, we evaluated the association between Lp(a) levels and coronary atherosclerotic burden, assessed by coronary arterty calcium (CAC) scores, in asymptomatic individuals with a family history of premature ASCVD. Lp(a) levels and other ASCVD risk factors were assessed in 432 individuals with premature ASCVD and in 937 healthy asymptomatic family members. CAC scores were only measured in asymptomatic family members. In this cohort, 16% had elevated Lp(a) levels, defined as ≥ 50 mg/dL. Among healthy family members, elevated Lp(a) levels were associated with both absolute CAC scores of ≥ 100 (odds ratio [OR] 1.79 [95% confidence interval {CI} 1.13-2.83]) as well as with age- and gender-corrected CAC scores ≥ 80th percentile (OR 1.69 [95% CI 1.14-2.50]). This coincides with a higher prevalence of cardiovascular events (OR 1.48 [95% CI 1.11-2.01]) in the whole cohort. Elevated Lp(a) levels were associated with higher CAC scores, both absolute as well as age- and gender-corrected percentiles, in individuals with a family history of premature ASCVD. These data imply that Lp(a) accelerates progression of atherosclerosis in these individuals, thereby contributing to their increased ASCVD risk. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography

PubMed Central

Elmaleh, D. R.; Fischman, A. J.; Tawakol, A.; Zhu, A.; Shoup, T. M.; Hoffmann, U.; Brownell, A.-L.; Zamecnik, P. C.

2006-01-01

Diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and its analog P2,P3-monochloromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P2,P3-[18F]monofluoromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate ([18F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [18F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [18F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [18F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [18F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [18F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. PMID:17038498

Cocaine-induced microvascular vasoconstriction but differential systemic haemodynamic responses in Yucatan versus Yorkshire varieties of swine.

PubMed Central

Miao, L.; Núñez, B. D.; Susulic, V.; Wheeler, S.; Carrozza, J. P.; Ross, J. N.; Morgan, J. P.

1996-01-01

1. Systemic and coronary haemodynamics were measured in 6 Yorkshire swine and 6 Yucatan miniature swine under isoflurane anaesthesia to investigate the influence of cocaine following its intravenous administration at 1, 3 and 7 mg kg-1. 2. Cocaine in Yorkshire swine decreased mean arterial pressure and rate pressure product (systolic pressure x heart rate), suggesting a cardiac depressant effect, whereas cocaine in Yucatan miniature swine increased these parameters, consistent with a hyperadrenergic state. 3. Cocaine in both Yorkshire swine and Yucatan miniature swine decreased coronary blood flow and coronary flow reserve, and increased coronary vascular resistance. 4. A modest generalized epicardial coronary artery constriction was observed by angiography, without evidence of focal spasm. 5. Our results confirm a marked vasoconstrictor effect of cocaine on the coronary arterial circulation, predominantly distal to the epicardial coronary arteries, but also indicate important differences in the systemic cardiovascular responses to the drug between two closely related strains of animals within the same species. Due to the similarities between the swine and human coronary arterial vasculature, we suggest that vasoconstriction in the coronary microcirculation may produce cardiac toxicity in man. PMID:8821549

Predicting haemodynamic networks using electrophysiology: The role of non-linear and cross-frequency interactions

PubMed Central

Tewarie, P.; Bright, M.G.; Hillebrand, A.; Robson, S.E.; Gascoyne, L.E.; Morris, P.G.; Meier, J.; Van Mieghem, P.; Brookes, M.J.

2016-01-01

Understanding the electrophysiological basis of resting state networks (RSNs) in the human brain is a critical step towards elucidating how inter-areal connectivity supports healthy brain function. In recent years, the relationship between RSNs (typically measured using haemodynamic signals) and electrophysiology has been explored using functional Magnetic Resonance Imaging (fMRI) and magnetoencephalography (MEG). Significant progress has been made, with similar spatial structure observable in both modalities. However, there is a pressing need to understand this relationship beyond simple visual similarity of RSN patterns. Here, we introduce a mathematical model to predict fMRI-based RSNs using MEG. Our unique model, based upon a multivariate Taylor series, incorporates both phase and amplitude based MEG connectivity metrics, as well as linear and non-linear interactions within and between neural oscillations measured in multiple frequency bands. We show that including non-linear interactions, multiple frequency bands and cross-frequency terms significantly improves fMRI network prediction. This shows that fMRI connectivity is not only the result of direct electrophysiological connections, but is also driven by the overlap of connectivity profiles between separate regions. Our results indicate that a complete understanding of the electrophysiological basis of RSNs goes beyond simple frequency-specific analysis, and further exploration of non-linear and cross-frequency interactions will shed new light on distributed network connectivity, and its perturbation in pathology. PMID:26827811

Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease

PubMed Central

Bansal, Nisha; McCulloch, Charles E.; Lin, Feng; Robinson-Cohen, Cassianne; Rahman, Mahboob; Kusek, John W.; Anderson, Amanda H.; Xie, Dawei; Townsend, Raymond R.; Lora, Claudia M.; Wright, Jackson; Go, Alan S.; Ojo, Akinlolu; Alper, Arnold; Lustigova, Eva; Cuevas, Magda; Kallem, Radhakrishna; Hsu, Chi-yuan

2016-01-01

Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1,795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate under 30 ml/min/1.73 m2 and not on dialysis. The association of systolic (SBP), diastolic (DBP) and pulse pressure with risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction or peripheral arterial disease) and heart failure were tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46, 2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54, 4.11]) for DBP over 90 vs under 80 mmHg and higher pulse pressure (2.67 [1.82, 3.92]) for pulse pressure over 68 vs under 51 mmHg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05, 1.92]) for pulse pressure over 68 vs under 51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP and pulse pressure with risk of atherosclerotic CVD, while only higher pulse pressure was independently associated with greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure reduces the risk of CVD events in patients with stage 4 and 5 chronic kidney disease. PMID:27717485

Detection and characterization of atherosclerotic plaques by Raman probe spectroscopy and optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Schie, Iwan; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

2017-02-01

Visualization and characterization of inner arterial plaque depositions is of vital diagnostic interest. Established intravascular imaging techniques provide valuable morphological information, but cannot deliver information about the chemical composition of individual plaques. Probe based Raman spectroscopy offers the possibility for a biochemical characterization of atherosclerotic plaque formations during an intravascular intervention. From post mortem studies it is well known that the severity of a plaque and its stability are strongly correlated with its biochemical composition. Especially the identification of vulnerable plaques remains one of the most important and challenging aspects in cardiology. Thus, specific information about the composition of a plaque would greatly improve the risk assessment and management. Furthermore, knowledge about the composition can offer new therapeutic and medication strategies. Plaque calcifications as well as major lipid components such as cholesterol, cholesterol esters and triglycerides can be spectroscopically easily differentiated. Intravascular optical coherence tomography (OCT) is currently a prominent catheter based imaging technique for the localization and visualization of atherosclerotic plaque depositions. The high resolution of OCT with 10 to 15 µm allows for very detailed characterization of morphological features such as different plaque formations, thin fibrous caps and accurate measurements of lesion lengths. In combination with OCT imaging the obtained spectral information can provide substantial information supporting on on-site diagnosis of various plaque types and therefor an improved risk assessment. The potential and feasibility of combining OCT with Raman spectroscopy is demonstrated on excised plaque samples, as well as under in vivo conditions. Acknowledgements: Financial support from the Carl Zeiss Foundation is greatly acknowledged.

Increased popliteal circumferential wall tension induced by orthostatic body posture is associated with local atherosclerotic plaques.

PubMed

Gemignani, Tiago; Azevedo, Renata C; Higa, Celina M; Coelho, Otávio R; Matos-Souza, José R; Nadruz, Wilson

2012-09-01

Lower limb arteries are exposed to higher hemodynamic burden in erectile posture. This study evaluated the effects of body posture on popliteal, carotid and brachial circumferential wall tension (CWT) and investigated the relationship between local CWT and atherosclerotic plaques in subjects with cardiovascular risk factors. Two hundred and three subjects (118 women and 85 men) with cardiovascular risk factors (smoking, hypertension or diabetes mellitus) underwent clinical and laboratory analysis and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Arteries were evaluated by ultrasound analysis, while CWT was calculated according to Laplace's law. Among the enrolled participants, 47%, 29% and none presented popliteal, carotid and brachial plaques, respectively. Carotid CWT measurements were not associated with local plaques after adjustment for potential confounders. Conversely, general linear model and logistic regression analyses adjusted for potential confounders demonstrated that peak orthostatic CWT was the only local hemodynamic parameter showing significant relationship with popliteal plaques in the whole sample. In gender-specific analyses, although positively correlated with popliteal plaques in both genders, local peak orthostatic CWT exhibited an independent association with popliteal plaques after adjustment for potential confounders only in women. Popliteal CWT measured in orthostatic posture, rather than in supine position, is associated with popliteal atherosclerotic plaques, particularly in women. These findings suggest that erectile posture might play a role in the atherogenesis of leg arteries by modifying local hemodynamic forces and that there may be gender differences in this regard. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography.

PubMed

Oh, Junghwan; Feldman, Marc D; Kim, Jihoon; Sanghi, Pramod; Do, Dat; Mancuso, J Jacob; Kemp, Nate; Cilingiroglu, Mehmet; Milner, Thomas E

2008-01-01

We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of < 40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster.

Association of postalimentary lipemia with atherosclerotic manifestations.

PubMed

Tentor, J; Nakamura, R T; Gidlund, M; Barros-Mazon, S; Harada, L M; Zago, V S; Oba, J F; Faria, E C de

2012-11-01

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Suppression of atherosclerotic changes in cholesterol-fed rabbits treated with an oral inhibitor of neutral endopeptidase 24.11 (EC 3.4.24.11).

PubMed

Kugiyama, K; Sugiyama, S; Matsumura, T; Ohta, Y; Doi, H; Yasue, H

1996-08-01

Neutral endopeptidase 24.11 (NEP), widely distributed in the body, hydrolyzes and inactivates a number of endogenous vasoactive peptides, some of which could alter various functions of cells present in the arterial wall. Recently NEP has been found to exist in the vascular endothelium. The aim of this study was to assess the influence of chronic NEP inhibition by daily administration of UK79300 (candoxatril), an orally active NEP inhibitor (NEPI), on the development of atherosclerotic changes in high-cholesterol-fed rabbits. Male New Zealand White rabbits were fed for 8 weeks as follows: normal rabbit diet (Normal, n = 15), 1.5% cholesterol diet (Cholesterol, n = 15), or 1.5% cholesterol diet containing NEPI (20 mg.kg-1.d-1) (Cholesterol+NEPI, n = 15). At the end of the dietary period, NEPI treatment was found to suppress the surface area of the aorta covered by plaques (% surface area: Cholesterol, 59 +/- 6 versus Cholesterol+NEPI, 36 +/- 7, P < .01) and decreased contents of cholesterol and cholesterol esters in the aortas. NEPI also reduced plasma total cholesterol by 27% of Cholesterol rabbits (1781 +/- 130 mg/dL). The endothelial function, estimated by the endothelium-dependent relaxation of the isolated aortas in response to acetylcholine, was preserved in Cholesterol+NEPI rabbits compared with that in Cholesterol rabbits. NEP enzymatic activities in plasma and the particulate fraction of the homogenates from the aortas in Cholesterol rabbits were both increased, 3.1- and 3.9-fold, respectively, above those in Normal rabbits, but the activities in Cholesterol+NEPI rabbits were significantly lower than those in Cholesterol rabbits. UK73967, an active form of UK79300, or phosphoramidon partly reversed the atherosclerotic impairment of relaxation of the isolated thoracic aortic rings from Cholesterol rabbits in response to exogenous additions of C-type natriuretic peptide (CNP) and substance P, which are NEP substrates known to exist endogenously in the vascular

Markers of immunity and bacterial translocation in cirrhosis.

PubMed

Mortensen, Christian

2015-07-01

Bacterial translocation (BT), the migration of enteric bacteria to extraintestinal sites, is related to immune stimulation and haemodynamic changes in experimental cirrhosis. These changes may be highly relevant to patients with cirrhosis, where changes in the circulation cause serious complications. The optimal surrogate marker of BT in patients with cirrhosis, however, is a matter of controversy. In the first study, we investigated the relationship between markers of inflammation, haemodynamics and prognosis in 45 patients and 12 controls. We found high-sensitive C-reactive protein to be correlated to portal hypertension, a clinically relevant haemodynamic alteration, and appeared to be associated with increased mortality. To assess the consequences of BT on immunity, we developed an assay for the detection of bacterial DNA (bDNA), a novel marker of BT. Using the assay in the second study, in 38 patients with ascites, we found no association between bDNA and immunity, in contrast to some previous findings. In the final paper, exploring one possible translocation route, we hypothesized a difference in bDNA levels between the blood from the veins draining the gut on one hand and the liver on the other. Collecting samples during the insertion of a shunt between the two vessels in 28 patients, our finding did not suggest marked differences in bDNA, but conversely to expectations, suggested marked hepatic production of two markers of inflammation. The main results of the present thesis support some concepts of current thinking on cirrhosis pathophysiology, including the relationship of markers of inflammation to  haemodynamics, disease stage and prognosis. Our results also add to a growing body of evidence suggesting that bDNA is not a clinically relevant marker of BT.

Deceleration time of left ventricular outflow tract flow as a simple surrogate marker for central haemodynamics at rest and as well as during exercise.

PubMed

Cho, In-Jeong; Shim, Chi Young; Moon, Sun-Ha; Lee, Hyun-Jin; Hong, Geu-Ru; Chung, Namsik; Ha, Jong-Won

2017-05-01

The shape and duration of left ventricular outflow tract (LVOT) flow has not been applied to assess the central haemodynamics, although LVOT flow is confronted with afterload of arterial system during systole. The aim of this study was to evaluate whether the LVOT flow parameters are related with central systolic blood pressure (BP) and arterial compliance at rest and as well as during exercise. We studied 258 subjects (175 females, age 61 ± 11 years) with normal left ventricular (LV) systolic function who underwent supine bicycle stress echocardiography and arterial tonometry simultaneously at rest and at peak exercise. Deceleration time (DT) of LVOT flow and RR interval were measured and deceleration time corrected for heart rate (DTc) was calculated. Peripheral and central haemodynamic parameters including systolic and diastolic BP, and augmentation index at a heart rate of 75 (AIx@75) were assessed using radial artery tonometry. Carotid femoral pulse wave velocity (PWV) was measured. Deceleration time corrected for heart rate was independently associated with central systolic BP and AIx@75 at rest (P < 0.001 and 0.006). Similarly, it also showed significant independent correlations with central systolic BP and AIx@75 during peak exercise (P = 0.006 and P = 0.021). In addition, DTc which measured both at rest and at peak exercise demonstrated significant positive correlations with PWV, suggesting association of prolonged DTc with arterial stiffening (P = 0.023 and P = 0.005). Prolongation of LVOT flow DTc represents raised central systolic BP and increased arterial stiffness not only at rest but also during exercise. Therefore, central aortic pressures and arterial stiffness influence the DT of LVOT flow at rest as well as during exercise in individuals with normal LV systolic function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Gold nanoparticles based imaging technique and drug delivery for the detection and treatment of atherosclerotic vascular disease

NASA Astrophysics Data System (ADS)

Ankri, Rinat; Leshem-Lev, Dorit; Lev, Eli I.; Motiei, Menachem; Hochhauser, Edith; Fixler, Dror

2016-03-01

In our study we aim to develop a new, simple and non-invasive method to detect and to treat atherosclerosis. We use gold nanoparticles (GNPs) combined with the diffusion reflection (DR) method to demonstrate the detection of vulnerable atherosclerotic plaques. Our method is based on the fact that macrophages are a major component in the vulnerable plaque and are able to uptake metal nanoparticles that can be discovered by the DR system. Moreover, it is well known that high density lipoprotein (HDL) reduces ASVD by inhibiting pro-inflammatory factors, enabling the specific treatment of atherosclerosis.

Magnetic resonance imaging-based computational modelling of blood flow and nanomedicine deposition in patients with peripheral arterial disease

PubMed Central

Hossain, Shaolie S.; Zhang, Yongjie; Fu, Xiaoyi; Brunner, Gerd; Singh, Jaykrishna; Hughes, Thomas J. R.; Shah, Dipan; Decuzzi, Paolo

2015-01-01

Peripheral arterial disease (PAD) is generally attributed to the progressive vascular accumulation of lipoproteins and circulating monocytes in the vessel walls leading to the formation of atherosclerotic plaques. This is known to be regulated by the local vascular geometry, haemodynamics and biophysical conditions. Here, an isogeometric analysis framework is proposed to analyse the blood flow and vascular deposition of circulating nanoparticles (NPs) into the superficial femoral artery (SFA) of a PAD patient. The local geometry of the blood vessel and the haemodynamic conditions are derived from magnetic resonance imaging (MRI), performed at baseline and at 24 months post intervention. A dramatic improvement in blood flow dynamics is observed post intervention. A 500% increase in peak flow rate is measured in vivo as a consequence of luminal enlargement. Furthermore, blood flow simulations reveal a 32% drop in the mean oscillatory shear index, indicating reduced disturbed flow post intervention. The same patient information (vascular geometry and blood flow) is used to predict in silico in a simulation of the vascular deposition of systemically injected nanomedicines. NPs, targeted to inflammatory vascular molecules including VCAM-1, E-selectin and ICAM-1, are predicted to preferentially accumulate near the stenosis in the baseline configuration, with VCAM-1 providing the highest accumulation (approx. 1.33 and 1.50 times higher concentration than that of ICAM-1 and E-selectin, respectively). Such selective deposition of NPs within the stenosis could be effectively used for the detection and treatment of plaques forming in the SFA. The presented MRI-based computational protocol can be used to analyse data from clinical trials to explore possible correlations between haemodynamics and disease progression in PAD patients, and potentially predict disease occurrence as well as the outcome of an intervention. PMID:25878124

Effect of rosuvastatin on atherosclerotic plaque stability: An intravascular ultrasound elastography study.

PubMed

Li, Zhaohuan; Wang, Lin; Hu, Xiaobo; Zhang, Pengfei; Chen, Yifei; Liu, Xinxin; Xu, Mingjun; Zhang, Yun; Zhang, Mei

2016-05-01

The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Control rabbits showed a significant increase in shear strain (SS) and area strain (AS) in total plaques. The rosuvastatin group showed no change in SS and AS, but serum TG and LDL-C levels were reduced, with less lipid deposition, macrophage infiltration, production of proinflammatory cytokines and apoptosis in plaques. The changes in SS and AS from baseline between groups significantly differed (SS: 1.15 (1.96) % vs. -0.99 ± 2.83%, p = 0.013; AS: 1.25 (2.29) % vs. -1.67 ± 5.05%, p = 0.022). At follow-up, for controls, strain values were increased in the shoulder of eccentric plaques (SS: 2.66 ± 1.31% vs. 4.86 ± 1.93%, p = 0.016; AS: 4.45 ± 2.33% vs. 7.91 ± 2.74%, p = 0.009) but not the plaque body. Changes in SS and AS in the plaque shoulder differed between the control and rosuvastatin groups (SS: 2.20 ± 2.17% vs. -0.87 ± 3.31%, p = 0.028; AS: 2.10 (4.61) % vs. -2.75 ± 5.97%, p = 0.009). Rosuvastatin therapy in rabbits with atherosclerotic plaques led to less vulnerable plaque features. IVUSE is a very sensitive technique for detecting pharmacologically-induced mechanical changes in rabbit atherosclerotic plaques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cold pressor stimulus temperature and resting masseter muscle haemodynamics in normal humans.

PubMed

Maekawa, K; Kuboki, T; Clark, G T; Shinoda, M; Yamashita, A

1998-11-01

Cold pressor stimulation reportedly increases sympathetic nerve activity in human skeletal muscles. This study examined the effect of cold pressor stimulation on the resting haemodynamics of the right masseter muscle in normal individuals, using near-infrared spectroscopy. Nine healthy non-smoking males with no history of chronic muscle pain or vascular headaches participated. Their right hand was immersed in a water bath (4, 10, 15 degrees C) for exactly 1 min. Each trial lasted 7 min (1 min before, 1 min during, 5 min after stimulation) and a strictly random order was utilized for the three test temperatures and the mock trial. Masseter muscle haemoglobin concentration and oxygen saturation, as well as heart rate and blood pressure, were continuously recorded in each trial. After completing the four trials, each participant produced and sustained a 30-s maximum voluntary clench in the intercuspal position. Data across the four trials were baseline-corrected and then magnitude-normalized to the individual's highest absolute haemoglobin and oxygen signal during the 30-s maximal clenching effort. Haemoglobin and oxygen saturation increased progressively during cold pressor stimulation as the water temperature decreased (Hb, p < 0.0001; O2, p = 0.0327); very little effect was seen during the mock trial. Heart rate and blood pressure also increased progressively during the stimulation as the temperature decreased (heart rate, p = 0.0013; systolic blood pressure, p = 0.0042; diastolic blood pressure, p = 0.0156). These data suggest that cold pressor, stimulation induces a strong increase in intramuscular blood volume which appears to be due to both a local vasodilative response and increased cardiac output.

Contribution of intracranial vertebral artery asymmetry to vestibular neuropathy.

PubMed

Chuang, Y M; Chern, C M; Liao, W H; Hsu, L C; Lien, C F; Lirng, J F; Shiao, A S; Ko, J S C

2011-07-01

To test the hypothesis that vertebral artery hypoplasia (VAH) may affect the lateralisation of vestibular neuropathy (VN), probably through haemodynamic effect on the vestibular labyrinth. 69 patients with unilateral VN were examined with a magnetic resonance angiographic (MRA) and caloric test. 50 healthy subjects served as controls. The diagnosis of intracranial VAH was based on MRA if <0.22 cm in VA diameter and a diameter asymmetry index >40%. The authors then correlated the canal paretic side with the VAH side. MRA study revealed 29 VAH (right/left: 23/6) in VN subjects and six VAH in controls (right/left: 5/1). The RR of VAH in VN subjects compared with controls was elevated (RR=2.2; 95% CI 1.8 to 2.8). There was a high accordance rate between the side of VAH and VN. Among 29 patients with unilateral VAH, 65.5% (N=19) had an ipsilateral VN, in which left VAH showed a higher accordance rate (83.3%) than the right side (60.9%). VN subjects with vascular risk factors also had a higher VAH accordance rate (81%) than those without (25%). VAH may serve as a regional haemodynamic negative contributor and impede blood supply to the ipsilateral vestibular labyrinth, contributing to the development of VN, which could be enhanced by atherosclerotic risk factors and the left-sided location.

Paramagnetic Manganese in the Atherosclerotic Plaque of Carotid Arteries

PubMed Central

Chelyshev, Yury; Ignatyev, Igor; Zanochkin, Alexey; Mamin, Georgy; Sorokin, Boris; Sorokina, Alexandra; Lyapkalo, Natalya; Gizatullina, Nazima; Orlinskii, Sergei

2016-01-01

The search for adequate markers of atherosclerotic plaque (AP) instability in the context of assessment of the ischemic stroke risk in patients with atherosclerosis of the carotid arteries as well as for solid physical and chemical factors that are connected with the AP stability is extremely important. We investigate the inner lining of the carotid artery specimens from the male patients with atherosclerosis (27 patients, 42–64 years old) obtained during carotid endarterectomy by using different analytical tools including ultrasound angiography, X-ray analysis, immunological, histochemical analyses, and high-field (3.4 T) pulse electron paramagnetic resonance (EPR) at 94 GHz. No correlation between the stable and unstable APs in the sense of the calcification is revealed. In all of the investigated samples, the EPR spectra of manganese, namely, Mn2+ ions, are registered. Spectral and relaxation characteristics of Mn2+ ions are close to those obtained for the synthetic (nano) hydroxyapatite species but differ from each other for stable and unstable APs. This demonstrates that AP stability could be specified by the molecular organization of their hydroxyapatite components. The origin of the obtained differences and the possibility of using EPR of Mn2+ as an AP stability marker are discussed. PMID:28078287

[Study on the effect of rhizoma Chuanxiong, radix paeoniae rubra and the compound of their active ingredients, Xiongshao Capsule, on stability of atherosclerotic plaque in ApoE(-/-) mice].

PubMed

Xu, Hao; Wen, Chuan; Chen, Ke-Ji

2007-06-01

To observe the effect of Rhizoma chuanxiong (RC), Radix Paeoniae rubra (RP) and Xiongshao Capsule (XC, a compound of their active ingredients, Chuanxingols and Paeoniflorins) on stability of atherosclerotic plaque in ApoE-/- mice and to explore the probable mechanisms. The effect of RC, RP and XC in stabilizing atherosclerotic plaque, in terms of pathologic morphology, cell composition and inflammatory reaction, in the atherosclerosis model established on ApoE-/- mice was studied by using optical microscope, immunohistochemical method and computerized imaging analysis respectively. After the ApoE-/- mice being fed with high fat diet for 26 weeks, obvious atherosclerotic lesion with typical unstable characteristics was found in their aortic root. Both RC and RP had certain effects in lowering total cholesterol and increasing the thickness of fibre cap. RC could also lower the serum triglyceride (TC) level and the lipid-core/plaque area ratio as well as reduce the macrocytic infiltration. In addition to the same effects as above mentioned, XS could also raise the levels of high density lipoprotein-cholesterol (HDL-C), lower TC/HDL-C ratio, reduce inflammatory reaction and enlarge the collagen area in plaque. The acting links of RC and RP on atherosclerosis are different, the compound of their active ingredients, XS, shows a more evident effect in intervening unstable plaque. It demonstrates the effect-enhancing power of TCM compound and is worth further studying.

Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

PubMed

Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

2016-04-01

Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Basilar artery atherosclerotic plaques in paramedian and lacunar pontine infarctions: a high-resolution MRI study.

PubMed

Klein, Isabelle F; Lavallée, Philippa C; Mazighi, Mikael; Schouman-Claeys, Elisabeth; Labreuche, Julien; Amarenco, Pierre

2010-07-01

Pontine infarction is most often related to basilar artery atherosclerosis when the lesion abuts on the basal surface (paramedian pontine infarction), whereas small medial pontine lesion is usually attributed to small vessel lipohyalinosis. A previous study has found that high-resolution MRI can detect basilar atherosclerotic plaques in up to 70% of patient with paramedian pontine infarction, even in patients with normal angiograms, but none has evaluated the presence of basilar artery plaque by high-resolution MRI in patients with small medial pontine lesion in the medial part of the pons. Consecutive patients with pontine infarction underwent basilar angiography using time-of-flight and contrast-enhanced 3-dimensional MR angiography to assess the presence of basilar artery stenosis and high-resolution MRI to assess the presence of atherosclerotic plaque. Basilar artery angiogram was scored as "normal," "irregular," or "stenosed" >or=30%" and basilar artery by high-resolution MRI was scored as "normal" or "presence of plaque." Medial pontine infarcts were divided into paramedian pontine infarction and small medial pontine lesion groups. Forty-one patients with pontine infarction were included, 26 with paramedian pontine infarction and 15 with small medial pontine lesion. High-resolution MRI detected basilar artery atherosclerosis in 42% of patients with a pontine infarction and normal basilar angiograms. Among patients with paramedian pontine infarction, 65% had normal basilar angiograms but 77% had basilar artery atherosclerosis detected on high-resolution MRI. Among patients with small medial pontine lesion, 46% had normal basilar angiograms but 73% had basilar artery plaques detected on by high-resolution MRI. This study suggests that medial pontine lacunes may be due to a penetrating artery disease secondary to basilar artery atherosclerosis. High-resolution MRI could help precise stroke subtyping.

Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease.

PubMed

Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian; Gislason, Gunnar H; Køber, Lars; Jensen, Lisette Okkels; Thayssen, Per; Ravkilde, Jan; Tilsted, Hans-Henrik; Lassen, Jens Flensted; Thuesen, Leif

2013-05-01

Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease. This retrospective registry based cohort study included all patients from the Western Denmark Heart Registry with coronary atherosclerosis confirmed by coronary angiography from January 2000 to December 2010. Patients were divided into eight groups according to body mass index (BMI) based on WHO BMI classification. Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark. The study included 37 573 patients (70.7% men) with a mean age of (66.3 ± 11.1) years. During the 11 years of follow-up, 5866 (15.6%) patients died. Multivariable analysis confirmed that the risk of death was the lowest among the preobese patients (27.5 ≤ BMI<30 kg/m(2)) with adjusted HR of 0.82 (95% CI 0.71 to 0.95; p=0.008) and increased with both low (BMI<18.50 kg/m(2)) and very high (BMI ≥ 40 kg/m(2)) BMI, HR 2.04 (95% CI 1.63 to 2.57; p<0.001) and HR 1.35 (95% CI 1.05 to 1.72; p<0.01), respectively. Also the normal weight class I (18.5 ≤ BMI<23 kg/m(2)) had a significant risk of mortality HR 1.28 (95% CI 1.13 to 1.45; p<0.001). Obese classes I and II did not differ from the reference group (23 ≤ BMI<25 kg/m(2)). Overweight atherosclerotic heart disease patients have improved survival compared with normal weight patients. Underweight and severely obese patients have increased mortality. Our results lean more towards an overweight paradox than an obesity paradox.

Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease

PubMed Central

Araldi, Elisa; Chamorro-Jorganes, Aranzazu; van Solingen, Coen; Fernández-Hernando, Carlos; Suárez, Yajaira

2013-01-01

Atherosclerosis (also known as arteriosclerotic vascular disease) is a chronic inflammatory disease of the arterial wall, characterized by the formation of lipid-laden lesions. The activation of endothelial cells at atherosclerotic lesion–prone sites in the arterial tree results in the up-regulation of cell adhesion molecules and chemokines, which mediate the recruitment of circulating monocytes. Accumulation of monocytes and monocyte-derived phagocytes in the wall of large arteries leads to chronic inflammation and the development and progression of atherosclerosis. The lesion experiences the following steps: foam cell formation, fatty streak accumulation, migration and proliferation of vascular smooth muscle cells, and fibrous cap formation. Finally, the rupture of the unstable fibrous cap causes thrombosis in complications of advanced lesions that leads to unstable coronary syndromes, myocardial infarction and stroke. MicroRNAs have recently emerged as a novel class of gene regulators at the post-transcriptional level. Several functions of vascular cells, such as cell differentiation, contraction, migration, proliferation and inflammation that are involved in angiogenesis, neointimal formation and lipid metabolism underlying various vascular diseases, have been found to be regulated by microRNAs and are described in the present review as well as their potential therapeutic application. PMID:23713860

Comparison of Different Cuff Pressure Use with the Supreme Laryngeal Mask Airway on Haemodynamic Response, Seal Pressure and Postoperative Adverse Events: A Prospective Randomized Study.

PubMed

Ali, Achmet; Altun, Demet; Sivrikoz, Nukhet; Yornuk, Mesut; Turgut, Namigar; Akıncı, İbrahim Özkan

2018-04-01

The Supreme™ laryngeal mask airway (SLMA) is a supra glottic airway (SGA) device that is used as an alternative to endotracheal tubes. In the present study, we aimed to compare the use of the SLMA with normal cuff pressure and low cuff pressure, primarily for haemodynamic response. In the present study, 120 patients diagnosed with hypertension and scheduled for varicose vein or inguinal hernia operation were enrolled and 99 patients finished. Using randomization, patients were divided into two groups according to cuff pressure as a low-pressure group (Group L, 45 cm H 2 O) and a normal-pressure group (Group N, 60 cm H 2 O). Demographics, Mallampati score and the type and duration of surgery, heart rate (HR), mean arterial pressure (MAP), percentage of tidal volume leakage, Ppeak, Pmean, etCO 2 , seal pressure, fibreoptic scores and postoperative adverse effects of all patients were recorded. MAP and HR values immediately and 2 minutes after SLMA insertion were significantly lower in Group L (p<0.001). In Group L and Group N, the seal pressures were 24.1±3.1 cm H 2 O and 26.2±3.9 cm H 2 O, respectively (p=0.003). Also, blood staining and sore throat occurred less frequently in Group L (p<0.05). The fibreoptic average score, insertion features and ventilation parameters were similar between the groups (p>0.05). SLMA use with a cuff pressure of 45 cm H 2 O significantly decreases haemodynamic response and post-operative side effects compared with a normal cuff pressure. Therefore, except for some specific surgeries that require higher seal pressures, we recommend the use of the SLMA with cuff pressures as low as 45 cm H 2 O.

Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreased steatosis in ApoE null mice fed atherogenic diet.

PubMed

Dhar-Mascareno, Manya; Rozenberg, Inna; Iqbal, Jahangir; Hussain, M Mahmood; Beckles, Daniel; Mascareno, Eduardo

2017-02-01

Hexim-1 is an inhibitor of RNA polymerase II transcription elongation. Decreased Hexim-1 expression in animal models of chronic diseases such as left ventricular hypertrophy, obesity and cancer triggered significant changes in adaptation and remodeling. The main aim of this study was to evaluate the role of Hexim1 in lipid metabolism focused in the progression of atherosclerosis and steatosis. We used the C57BL6 apolipoprotein E (ApoE null) crossed bred to C57BL6Hexim1 heterozygous mice to obtain ApoE null - Hexim1 heterozygous mice (ApoE-HT). Both ApoE null backgrounds were fed high fat diet for twelve weeks. Then, we evaluated lipid metabolism, atherosclerotic plaque formation and liver steatosis. In order to understand changes in the transcriptome of both backgrounds during the progression of steatosis, we performed Affymetrix mouse 430 2.0 microarray. After 12 weeks of HFD, ApoE null and ApoE-HT showed similar increase of cholesterol and triglycerides in plasma. Plaque composition was altered in ApoE-HT. Additionally, liver triglycerides and steatosis were decreased in ApoE-HT mice. Affymetrix analysis revealed that decreased steatosis might be due to impaired inducible SOCS3 expression in ApoE-HT mice. In conclusion, decreased Hexim-1 expression does not alter cholesterol metabolism in ApoE null background after HFD. However, it promotes stable atherosclerotic plaque and decreased steatosis by promoting the anti-inflammatory TGFβ pathway and blocking the expression of the inducible and pro-inflammatory expression of SOCS3 respectively. Published by Elsevier Ltd.

Effects of ageing and Alzheimer disease on haemodynamic response function: a challenge for event-related fMRI.

PubMed

Asemani, Davud; Morsheddost, Hassan; Shalchy, Mahsa Alizadeh

2017-06-01

Functional magnetic resonance imaging (fMRI) can generate brain images that show neuronal activity due to sensory, cognitive or motor tasks. Haemodynamic response function (HRF) may be considered as a biomarker to discriminate the Alzheimer disease (AD) from healthy ageing. As blood-oxygenation-level-dependent fMRI signal is much weak and noisy, particularly for the elderly subjects, a robust method is necessary for HRF estimation to efficiently differentiate the AD. After applying minimum description length wavelet as an extra denoising step, deconvolution algorithm is here employed for HRF estimation, substituting the averaging method used in the previous works. The HRF amplitude peaks are compared for three groups HRF of young, non-demented and demented elderly groups for both vision and motor regions. Prior works often reported significant differences in the HRF peak amplitude between the young and the elderly. The authors' experimentations show that the HRF peaks are not significantly different comparing the young adults with the elderly (either demented or non-demented). It is here demonstrated that the contradictory findings of the previous studies on the HRF peaks for the elderly compared with the young are originated from the noise contribution in fMRI data.

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

PubMed Central

Anderson, W P; Johnston, C I; Korner, P I

1979-01-01

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

Ten good reasons why everybody can and should perform cardiac ultrasound in the ICU.

PubMed

Charron, Cyril; Repessé, Xavier; Bodson, Laurent; Au, Siu-Ming; Vieillard-Baron, Antoine

2014-01-01

Critical care ultrasonography (CCUS) has been defined as an ultrasound evaluation of the heart, abdomen, pleura and lungs at the bedside by the intensivist, 24/7. Within CCUS, critical care echocardiography (CCE) is used to assess cardiac function and more generally haemodynamics. Experts in haemodynamics have published a 'consensus of 16' regarding an update on haemodynamic monitoring. They reported the ten key properties of an 'ideal' haemodynamic monitoring system, which perfectly match the ten good reasons we describe here for performing CCE in critically ill patients. Even though unfortunately no evidence-based medicine study is available to support this review, especially regarding CCE-related improvement of outcome, many clinical studies have demonstrated that CCE provides measurements of relevant, accurate, reproducible and interpretable variables, is easy to use, readily available, has a rapid response time, causes no harm, and is cost-effective. Whether it is operator-independent is obviously more debatable and is discussed in this review. All these characteristics are arguments for the extensive use of CCE by intensivists. This is why experts in the field have recommended that a basic level of CCE should be included in the training of all intensivists.

An Evaluation of the Numbers and Locations of Coronary Artery Disease with Some of the Major Atherosclerotic Risk Factors in Patients with Coronary Artery Disease

PubMed Central

Naghshtabrizi, Behshad; Moradi, Abbas; Amiri, Jalaleddin; Aarabi, Sepide

2017-01-01

Introduction Despite definite recognition of major atherosclerotic risk factors, the relationship between the pattern of coronary artery disease and these risk factors is unknown. Aim The aim of this study was to identify the relationship between some of the major atherosclerotic risk factors and the number and pattern of coronary artery disease in patients with coronary artery disease who presented to Farshchian Heart University Hospital, Hamadan, Iran. Materials and Methods In this descriptive cross-sectional study, we investigated some of the major atherosclerotic risk factors and their relationships with the type of coronary artery disease in terms of number and location of disease. A total of 1100 patients were enrolled with coronary artery disease confirmed by selective coronary angiography from 2010-2014. A p-value<0.05 was considered statistically significant. Results A total of 1100 patients enrolled in this study. The patient population consisted of 743 (67.5%) males and 357 (32.5%) females. A meaningful relationship existed between ageing, diabetes mellitus, hypertension and 3-Vessel Disease (3VD, p<0.001) as well as between hyperlipidemia and Single Vessel Disease (SVD, p<0.001). Patients diagnosed with diabetes mellitus, hypertension, and hyperlipidemia showed greater potential to develop coronary artery disease at the proximal section of the coronary arteries. Conclusion Based on the relationship between some of the major risk factors and the pattern of coronary artery disease in the current study, prospective studies should investigate other risk factors. We recommend that a plan should be developed to reduce adjustable risk factors such as diabetes mellitus, hypertension and hyperlipidemia in order to decrease coronary artery disease. PMID:28969179

TU-F-12A-06: BEST IN PHYSICS (IMAGING) - A Novel Catheter-Based Radionuclide Imaging System to Characterize Atherosclerotic Plaque

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaman, R; Kosuge, H; Carpenter, C

2014-06-15

Purpose: Atherosclerosis underlies coronary artery diseases, the leading cause of death in the United States and worldwide. In this study, we developed a novel catheter-based radionuclide imaging (CRI) system to image 18F-fluorodeoxyglucose (18F-FDG), a radionuclide, a marker of vascular inflammation, in murine carotid arteries and characterized the system for spatial resolution from multiple scintillating materials. Methods: The catheter system includes 35 mm and 8 mm fixed focal length lenses, which are subsequently connected to a CMOS camera and fiber holder. The distal ferrule of an image bundle is terminated with a wide-angle lens. The novelty of this system is amore » scintillating balloon with a crystal tip in the front of the wide angle lens to image light from the decay of 18F-FDG emission signal. The scintillating balloon is fabricated from 1mL of silicone RTV catalyst mixed with 1 mL base and 50 mg/mL calcium fluoride doped with Europium (CaF2:Eu). To identify the optimal scintillating materials with respect to resolution, we calculated modulation transfer function (MTF) of Yttrium Aluminum Garnet doped with Cerium (YAG:Ce), anthracene, and CaF2:Eu phosphors using a thin line optical phantom (Fig. 1a-1b). Macrophage-rich FVB murine atherosclerotic carotid plaque model (n = 4) was used in ex vivo experiments. Confirmatory imaging was also performed by an external optical imaging system (IVIS-200). Results: Analysis of the different phosphors (Fig 1b) showed that CaF2:Eu enabled the best resolution of 1.2μm. The CRI system visualized 18F-FDG in atherosclerotic plaques (Fig. 1d). The ligated left carotid (LR) artery exhibited 4× higher 18F-FDG signal intensity compared to the non-ligated right carotid (negative control) artery (1.65×10{sup 2} ±4.07×10{sup 1} vs. 4.44×10{sup 1}±2.17×10{sup 0}, A.U., p = 0.005) and confirmed with IVIS-200 (Fig. 1d). Conclusion: This CRI system enables high-resolution and sensitive detection of 18F-FDG uptake by

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.

PubMed

Tarkin, Jason M; Joshi, Francis R; Evans, Nicholas R; Chowdhury, Mohammed M; Figg, Nichola L; Shah, Aarti V; Starks, Lakshi T; Martin-Garrido, Abel; Manavaki, Roido; Yu, Emma; Kuc, Rhoda E; Grassi, Luigi; Kreuzhuber, Roman; Kostadima, Myrto A; Frontini, Mattia; Kirkpatrick, Peter J; Coughlin, Patrick A; Gopalan, Deepa; Fryer, Tim D; Buscombe, John R; Groves, Ashley M; Ouwehand, Willem H; Bennett, Martin R; Warburton, Elizabeth A; Davenport, Anthony P; Rudd, James H F

2017-04-11

Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET), [ 18 F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. This study tested the efficacy of gallium-68-labeled DOTATATE ( 68 Ga-DOTATATE), a somatostatin receptor subtype-2 (SST 2 )-binding PET tracer, for imaging atherosclerotic inflammation. We confirmed 68 Ga-DOTATATE binding in macrophages and excised carotid plaques. 68 Ga-DOTATATE PET imaging was compared to [ 18 F]FDG PET imaging in 42 patients with atherosclerosis. Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68 Ga-DOTATATE ligand binding to SST 2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68 Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68 Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBR max ) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68 Ga-DOTATATE mTBR max predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [ 18 F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [ 18 F]FDG mTBR max differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [ 18 F]FDG spillover rendered coronary

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi;

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

PubMed Central

Levine, Benjamin D; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Zuckerman, Julie H; Diedrich, André; Biaggioni, Italo; Ray, Chester A; Smith, Michael L; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D; Buckey, Jay C; Cooke, William H; Baisch, Friedhelm J; Robertson, David; Eckberg, Dwain L; Blomqvist, C Gunnar

2002-01-01

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts ∼72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (± s.e.m.) stroke volume was lower (46 ± 5 vs. 76 ± 3 ml, P = 0.017) and heart rate was higher (93 ± 1 vs. 74 ± 4 beats min−1, P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 ± 256 vs. 1372 ± 62 dynes s cm−5, P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 ± 4 vs. 17 ± 2 bursts min−1, P = 0.04) and tilted (46 ± 4 vs. 38 ± 3 bursts min−1, P = 0.01) positions. A strong (r2 = 0.91–1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal. PMID:11773340

Quantitative T1 and T2* carotid atherosclerotic plaque imaging using a three-dimensional multi-echo phase-sensitive inversion recovery sequence: a feasibility study.

PubMed

Fujiwara, Yasuhiro; Maruyama, Hirotoshi; Toyomaru, Kanako; Nishizaka, Yuri; Fukamatsu, Masahiro

2018-06-01

Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T 1 -weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T 1 -weighted and T 2 *-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T 1 and T 2 * values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of an IPH. T 1 and T 2 * values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T 1 and T 2 * values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T 1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T 1 and T 2 * values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components.

Haploinsufficiency of E-selectin ligand-1 is Associated with Reduced Atherosclerotic Plaque Macrophage Content while Complete Deficiency Leads to Early Embryonic Lethality in Mice

PubMed Central

Luo, Wei; Wang, Hui; Guo, Chiao; Wang, Jintao; Kwak, Jeffrey; Bahrou, Kristina L; Eitzman, Daniel T.

2012-01-01

E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/-) were intercrossed to produce ESL-1-/- mice, however ESL-1-/- mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE-/-), ESL-1+/- mice were generated and fed western diet. Compared to ApoE-/-, ESL-1++ mice, atherosclerotic lesions from ApoE-/-, ESL-1+/- contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality. PMID:22939356

Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

PubMed Central

Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

2017-01-01

The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice

PubMed Central

Lutz, Manfred B.; Zernecke, Alma

2014-01-01

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr −/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr −/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l −/−) mice, a specific loss of CD103+ DCs but also CD103− CD11b+ F4/80− DCs was evidenced. Aortic CD103+ and CD11b+ F4/80− CD103− DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103− CD11b+ F4/80− and CD11b+ F4/80+ cells in atherosclerotic Ldlr −/− mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80− DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation. PMID:24551105

Atherosclerotic vascular disease in systemic lupus erythematosus.

PubMed

Liang, Matthew H; Mandl, Lisa A; Costenbader, Karen; Fox, Ervin; Karlson, Elizabeth

2002-09-01

In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority.

Dickkopf1 destabilizes atherosclerotic plaques and promotes plaque formation by inducing apoptosis of endothelial cells through activation of ER stress

PubMed Central

Di, Mingxue; Wang, Lin; Li, Mengmeng; Zhang, Yu; Liu, Xinxin; Zeng, Renya; Wang, Han; Chen, Yifei; Chen, Weijia; Zhang, Yun; Zhang, Mei

2017-01-01

Several clinical studies reported that Dickkopf1 (DKK1) plasma levels are correlated with atherosclerosis. However, the impact of DKK1 on the formation and vulnerability of atherosclerotic plaques remains elusive. This study investigated DKK1’s effects on enlargement and destabilization of plaques by targeting endothelial cells and assessing the possible cellular mechanisms involved. The effects of DKK1 on atherogenesis and plaque stability were evaluated in ApoE−/− mice using lentivirus injections to knockdown and knock-in the DKK1 gene. The presence of DKK1 resulted in enlarged and destabilized atherosclerotic lesions and increased apoptosis, while silencing of DKK1 alleviated plaque formation and vulnerability in the whole progression of atherosclerosis. DKK1 expression was upregulated in response to ox-LDL treatment in a time- and concentration-dependent manner on human umbilical vein endothelial cell (HUVEC). The interference of DKK1 reversed ox-LDL-induced apoptosis in HUVECs. The mechanism underlying this effect was DKK1’s activation of the JNK signal transduction pathway and inhibition of canonical Wnt signaling, following by activation of the IRE1α and eif2α/CHOP pathways. In conclusion, DKK1 promotes plaque formation and vulnerability partly by inducing apoptosis in endothelial cells, which partly through inducing the JNK-endoplasmic reticulum stress pathway and inhibiting canonical Wnt signaling. PMID:28703797

An increased waist-to-hip ratio is a key determinant of atherosclerotic burden in overweight subjects.

PubMed

Scicali, Roberto; Rosenbaum, David; Di Pino, Antonino; Giral, Philippe; Cluzel, Philippe; Redheuil, Alban; Piro, Salvatore; Rabuazzo, Agata Maria; Purrello, Francesco; Bruckert, Eric; Gallo, Antonio

2018-04-21

The association of overweight status and cardiovascular disease is not clear. In this study we aimed to investigate coronary atherosclerotic disease, evaluated as coronary artery calcium score (CACs), in overweight patients with or without abdominal obesity as defined by waist-to-hip ratio (WHR). We enrolled 276 patients aged between 40 and 70 years, with a body mass index of 25-29.9 kg/m 2 and at least one cardiovascular risk factor. Exclusion criteria were history of diabetes, cardiovascular or renal disease. Patients were stratified in high WHR (H-WHR) or low WHR (L-WHR) group according to WHR (≥ 0.85 for women and ≥ 0.90 for men) and underwent multi-detector computed tomography for CACs. Mean carotid intima-media thickness (IMT) and plaque presence were equally assessed. CACs was higher in the H-WHR group compared to L-WHR (9.05 [0.0-83.48] vs 0.0 [0.0-64.7] AU, p < 0.01); the prevalence of CACs > 0 in the H-WHR group was significantly higher than subjects with L-WHR (59.6% vs 38.5%, p < 0.001). Moreover, H-WHR group had higher mean IMT (0.64 [0.56-0.72] vs 0.59 [0.55-0.67] mm, p < 0.05) and higher carotid plaque prevalence (63.7% vs 50.8%, p < 0.05) compared to subjects with L-WHR. Logistic regression showed that H-WHR was associated with presence of CACs and carotid plaque (p < 0.01). In a multiple linear regression, WHR was positively associated with CACs and IMT (p < 0.01). H-WHR is a marker of coronary and peripheral atherosclerotic burden in overweight patients.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe

2015-01-01

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Ten-year results of the Freedom Solo stentless heart valve: excellent haemodynamics but progressive valve dysfunction in the long term.

PubMed

Sponga, Sandro; Barbera, Mila Della; Pavoni, Daisy; Lechiancole, Andrea; Mazzaro, Enzo; Valente, Marialuisa; Nucifora, Gaetano; Thiene, Gaetano; Livi, Ugolino

2017-05-01

Freedom Solo (FS) is a pericardial stentless heart valve showing excellent haemodynamic performance at mid-term. The aim of this study was to evaluate the long-term performance of such bioprostheses. Between December 2004 and November 2009, 109 patients (31 men; mean age 76 ± 6 years) underwent aortic valve replacement with FS. Preoperatively, the mean NYHA class was 2.5 ± 0.7, the mean EuroSCORE II, 2.8 ± 2.5. Mean prosthesis size was 22.7 ± 1.9 mm; concomitant procedures were performed in 65 patients. Structural valve deterioration (SVD) was diagnosed according to the Valve Academic Research Consortium-2 definition. Two patients (1.8%) died within 30 days. Follow-up (72 ± 36 months) was 100% completed. The 1-, 5- and 10-year actuarial survival rates were 89, 73 and 42%, respectively, with 8 valve-related deaths; the actuarial freedom from SVD was 99, 93 and 76%. During 61 ± 39 months of follow-up, echocardiographic findings worsened progressively: At discharge, 3-5 and 7-9 years, the mean gradient was 8 ± 4, 12 ± 11 and 19 ± 19 mmHg ( P  < 0.01); the indexed effective orifice area was 1.0 ± 0.2, 0.9 ± 0.2 and 0.8 ± 0.3 cm 2 /m 2 ( P  < 0.01). Of the 13 patients who developed SVD, it was due to aortic stenosis in 11. SVD was a predictor of cardiovascular mortality at univariate analysis (HR 2.87, 1.12-7.29); 2 explanted prostheses showed massive calcium deposits with mean calcium and phosphorus contents of 234 ± 16 and 116 ± 7 mg/g dry weight, respectively. The FS bioprosthesis shows excellent mid-term clinical and haemodynamic results and offers an alternative to other valves, particularly in the case of a small aortic annulus. Worsening of FS performance was observed at late follow-up because of progressive SVD with stenosis, questioning whether it should be used in patients with a long life expectancy. © The Author 2017. Published by Oxford University Press on behalf of the

Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients

PubMed Central

Heidari, Mohammad Mehdi; Khatami, Mehri; Hadadzadeh, Mehdi; Kazemi, Mahbobeh; Mahamed, Sahar; Malekzadeh, Pegah; Mirjalili, Massomeh

2015-01-01

Background: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. Objectives: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-α (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. Patients and Methods: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF-α polymorphisms were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-α gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. Conclusions: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID:26878010