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1

Irbesartan but Not Amlodipine Suppresses Diabetes-Associated Atherosclerosis  

Microsoft Academic Search

Background—It remains controversial whether specific blockade of the renin-angiotensin system confers superior antiatherosclerotic effects over other antihypertensive agents in diabetes. Therefore, the aim of this study was to compare equihypotensive doses of the angiotensin II subtype 1 (AT1) receptor blocker irbesartan with the calcium antagonist amlodipine on diabetes-induced plaque formation in the apolipoprotein E (apoE)-null mouse and to explore molecular

Riccardo Candido; Terri J. Allen; Markus Lassila; Zemin Cao; Vicki Thallas; Mark E. Cooper; Karin A. Jandeleit-Dahm

2010-01-01

2

Irbesartan and Hydrochlorothiazide  

MedlinePLUS

Avalide® (as a combination product containing Irbesartan, Hydrochlorothiazide) ... Combination productThis product contains two medications, irbesartan and hydrochlorothiazide. Please see the individual monographs for information about ...

3

PPAR? regulates multiple proinflammatory pathways to suppress atherosclerosis  

PubMed Central

Lipid homeostasis and inflammation are key determinants in atherogenesis, exemplified by the requirement of lipid-laden, foam cell macrophages for atherosclerotic lesion formation. Although the nuclear receptor PPAR? has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic target in vascular disease is unclear. We show here that orally active PPAR? agonists significantly reduce atherosclerosis in apoE?/? mice. Metabolic and gene expression studies reveal that PPAR? attenuates lesion progression through its HDL-raising effect and anti-inflammatory activity within the vessel wall, where it suppresses chemoattractant signaling by down-regulation of chemokines. Activation of PPAR? also induces the expression of regulator of G protein signaling (RGS) genes, which are implicated in blocking the signal transduction of chemokine receptors. Consistent with this, PPAR? ligands repress monocyte transmigration and macrophage inflammatory responses elicited by atherogenic cytokines. These results reveal that PPAR? antagonizes multiple proinflammatory pathways and suggest PPAR?-selective drugs as candidate therapeutics for atherosclerosis. PMID:18337509

Barish, Grant D.; Atkins, Annette R.; Downes, Michael; Olson, Peter; Chong, Ling-Wa; Nelson, Mike; Zou, Yuhua; Hwang, Hoosang; Kang, Heonjoong; Curtiss, Linda; Evans, Ronald M.; Lee, Chih-Hao

2008-01-01

4

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages  

SciTech Connect

Highlights: ? We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ? Apocynin prevented atherosclerotic lesion formation. ? Apocynin suppressed ROS production in aorta and in macrophages. ? Apocynin suppressed cytokine expression and cell proliferation in macrophages. ? Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

2013-02-08

5

Suppression of experimental atherosclerosis by the Ca++-antagonist lanthanum. Possible role of calcium in atherogenesis.  

PubMed Central

Agents inhibiting calcium deposition into arteries are known to suppress atherosclerosis in animals. However, the precise role of calcium in atherogenesis is unknown. In this study, the specific Ca2+-antagonist lanthanum was used to attempt suppression of experimental atherosclerosis and to gain more insight into the possible effects of calcium on atherogenesis. Rabbits were fed an atherogenic diet with and without increasing doses of LaCl3. All cholesterol-fed rabbits showed marked increases in serum cholesterol and ca2+. Untreated atherogenic animals revealed pronounced gross and microscopic atherosclerosis and striking increases in the aortic content of cholesterol, collagen, "elastin," and calcium as well as of elastin calcium, polar amino acids, and cholesterol. With increasing LaCl3 dosage these abnormalities progressively decreased and were completely abolished at the highest dose. The ingested La3+ was absorbed only in small quantities and had no discernible effect on the calcium and connective tissue content of bone, skin, lung, heart, and skeletal muscle nor on myocardial function (left ventricle pressure and left ventricle dp/dt) or myocardial and muscle content in ATP and creatine phosphate. The data suggest that shifts in arterial Ca2+-distribution may play a decisive part in atherogenesis, and provision of arterial calcium homeostasis by La3+ a pivotal role in its prevention, despite hypercholesteremia. Other inhibitors of calcium deposition into arteries may exert their protective effect by similar mechanisms. However, a direct inhibition of atherogenesis by La3+ cannot entirely be ruled out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported. Images PMID:7364947

Kramsch, D M; Aspen, A J; Apstein, C S

1980-01-01

6

Inhibiting DNA Methylation by 5-Aza-2'-deoxycytidine Ameliorates Atherosclerosis Through Suppressing Macrophage Inflammation.  

PubMed

Inflammation marks all stages of atherogenesis. DNA hypermethylation in the whole genome or specific genes is associated with inflammation and cardiovascular diseases. Therefore, we aimed to study whether inhibiting DNA methylation by DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) ameliorates atherosclerosis in low-density lipoprotein receptor knockout (Ldlr(-/-)) mice. Ldlr(-/-) mice were fed an atherogenic diet and adminisered saline or 5-aza-dC (0.25 mg/kg) for up to 30 weeks. 5-aza-dC treatment markedly decreased atherosclerosis development in Ldlr(-/-) mice without changes in body weight, plasma lipid profile, macrophage cholesterol levels and plaque lipid content. Instead, this effect was associated with decreased macrophage inflammation. Macrophages with 5-aza-dC treatment had downregulated expression of genes involved in inflammation (TNF-?, IL-6, IL-1?, and inducible nitric oxidase) and chemotaxis (CD62/L-selectin, chemokine [C-C motif] ligand 2/MCP-1 [CCL2/MCP-1], CCL5, CCL9, and CCL2 receptor CCR2). This resulted in attenuated macrophage migration and adhesion to endothelial cells and reduced macrophage infiltration into atherosclerotic plaques. 5-aza-dC also suppressed macrophage endoplasmic reticulum stress, a key upstream signal that activates macrophage inflammation and apoptotic pathways. Finally, 5-aza-dC demethylated liver X receptor ? (LXR?) and peroxisome proliferator-activated receptor ?1 (PPAR?1) promoters, which are both enriched with CpG sites. This led to overexpression of LXR? and PPAR?, which may be responsible for 5-aza-dC's anti-inflammatory and atheroprotective effect. Our findings provide strong evidence that DNA methylation may play a significant role in cardiovascular diseases and serve as a therapeutic target for prevention and treatment of atherosclerosis. PMID:25251587

Cao, Qiang; Wang, Xianfeng; Jia, Lin; Mondal, Ashis K; Diallo, Abdoulaye; Hawkins, Gregory A; Das, Swapan K; Parks, John S; Yu, Liqing; Shi, Huidong; Shi, Hang; Xue, Bingzhong

2014-12-01

7

77 FR 1695 - Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets, 25 Milligrams/300...  

Federal Register 2010, 2011, 2012, 2013

...FDA-2011-P-0822] Determination That AVALIDE (Hydrochlorothiazide and Irbesartan), Oral Tablets...has determined that AVALIDE (hydrochlorothiazide and irbesartan), oral tablets...drug applications (ANDAs) for hydrochlorothiazide and irbesartan, oral...

2012-01-11

8

Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts  

Microsoft Academic Search

Accelerated atherosclerosis in patients with diabetes is a major cause of their morbidity and mortality, and it is unresponsive to therapy aimed at restoring relative euglycemia. In hyperglycemia, nonenzymatic glycation and oxidation of proteins and lipids results in the accumulation of irreversibly formed advanced glycation endproducts. These advanced glycation endproducts engage their receptor in cells of the blood vessel wall,

Lisa Park; Kathleen G. Raman; Kenneth J. Lee; Yan Lu; Luis J. Ferran; Wing Sun Chow; David Stern; Ann Marie Schmidt

1998-01-01

9

Suppression of Oxidative Stress as a Mechanism of Reduction of Hypercholesterolemic Atherosclerosis by Cyclooxygenase Inhibitors  

Microsoft Academic Search

Hypercholesterolemia increases the formation of arachidonic acid from membrane phospholipids. Reactive oxgyen species (ROS) are generated during the synthesis of prostaglandins (PGs) from arachidonic acid. ROS have been implicated in the development of hypercholesterolemic atherosclerosis. Inhibition of the synthesis of PGs by indomethacin or naproxen, therefore, should be able to prevent the generation of ROS and hence the development of

Paul Lee; Kailash Prasad

2003-01-01

10

Comprehensive overview: efficacy, tolerability, and cost-effectiveness of irbesartan  

PubMed Central

Background Hypertension represents a major health problem, affecting more than one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is considered to be a highly effective treatment in the management of hypertension. The purpose of this review is to evaluate the efficacy, safety and tolerability profile , and cost-effectiveness of treatment with irbesartan in hypertension. Methods A review of the literature was conducted using the electronic PubMed and Cochrane Library databases and the Health Economic Evaluations Database of search terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and the results were utilized. Results Findings from the present analysis show that irbesartan either as monotherapy or in combination with other antihypertensive agents can achieve significant reductions in blood pressure, both systolic and diastolic, compared with alternative treatment options. Irbesartan was also found to have a renoprotective effect independent of its blood pressure-lowering in patients with type 2 diabetes and nephropathy. Furthermore, irbesartan demonstrated an excellent safety and tolerability profile , with either lower or equal adverse events compared with placebo and other alternative treatments. In terms of economic analyses, compared with other antihypertensive therapy alternatives, irbesartan was found to be a preferred option, that is less costly and more effective. Conclusion The evidence indicates that treating patients with hypertension alone or with type 2 diabetes and nephropathy using irbesartan can control hypertension, prolong life, and reduce costs in relation to existing alternatives. PMID:24124375

Gialama, Fotini; Maniadakis, Nikos

2013-01-01

11

ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation  

PubMed Central

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall. We demonstrate that macrophage lipid body formation can be induced by modified lipoproteins or by inflammatory Toll-like receptor agonists. We used an unbiased approach to study the overlap in these pathways to identify regulators that control foam cell formation and atherogenesis. An analysis method integrating epigenomic and transcriptomic datasets with a transcription factor (TF) binding site prediction algorithm suggested that the TF ATF3 may regulate macrophage foam cell formation. Indeed, we found that deletion of this TF results in increased lipid body accumulation, and that ATF3 directly regulates transcription of the gene encoding cholesterol 25-hydroxylase. We further showed that production of 25-hydroxycholesterol (25-HC) promotes macrophage foam cell formation. Finally, deletion of ATF3 in Apoe?/? mice led to in vivo increases in foam cell formation, aortic 25-HC levels, and disease progression. These results define a previously unknown role for ATF3 in controlling macrophage lipid metabolism and demonstrate that ATF3 is a key intersection point for lipid metabolic and inflammatory pathways in these cells. PMID:22473958

Gold, Elizabeth S.; Ramsey, Stephen A.; Sartain, Mark J.; Selinummi, Jyrki; Podolsky, Irina; Rodriguez, David J.; Moritz, Robert L.

2012-01-01

12

Suppressive Impact of Anethum Graveolens Consumption on Biochemical Risk Factors of Atherosclerosis in Hypercholesterolemic Rabbits  

PubMed Central

Background: We aimed to determine the effects of Anethum graveolens (Dill) powder on postprandial lipid profile, markers of oxidation and endothelial activation when added to a fatty meal. Methods: In an experimental study, 32 rabbits were randomly designated into four diet groups: normal diet, high cholesterol diet (1%), high cholesterol diet plus 5% (w/w) dill powder and high cholesterol diet plus lovastatin (10 mg/kg, bw). The concentrations of glucose, total cholesterol (TC), low-density lipoproteins-cholesterol (LDL-C), alanine aminotransferase (alt), aspartate aminotransferase (ast), fibrinogen, factor VII, apolipoprotein B (ApoB), nitrite and nitrate were measured in blood samples following 15 h of fasting and 3 h after feeding. Results: Concurrent use of A. graveolens powder or lovastatin significantly decreased ALT, TC, glucose, fibrinogen and LDL-C values in comparison with hypercholesterolemic diet group (P < 0.05). Consumption of A. graveolens or lovastatin did not change factor VII, ApoB, nitrite and nitrate levels significantly in comparison with hypercholesterolemic diet group. Intake of A. graveolens significantly decreased serum AST compared to hypercholesterolemic diet. Conclusions: A. graveolens might have some protective values against atherosclerosis and that it significantly affects some biochemical risk factors of this disease. Our findings also confirm the potential harmful effects of oxidized fats and the importance of dietary polyphenols in the meal. PMID:24049614

Setorki, Mahbubeh; Rafieian-Kopaei, Mahmoud; Merikhi, Alireza; Heidarian, Esfandiar; Shahinfard, Najmeh; Ansari, Roya; Nasri, Hamid; Esmael, Nafiseh; Baradaran, Azar

2013-01-01

13

Efficient Flow Suppressed MRI Improves Inter-Scan Reproducibility of Carotid Atherosclerosis Plaque Burden Measurements  

PubMed Central

Background To determine if better flow-suppression can meaningfully improve the reproducibility of measurements associated with carotid atherosclerotic disease, particularly for lumen and wall areas. Methods Eighteen subjects with carotid artery stenosis identified by duplex ultrasound (11 with 16–49% stenosis; 7 with 50–79% stenosis) underwent two carotid MRI examinations on a 3T scanner with a 4-channel phased array coil. High-resolution intermediate-weighted TSE (TR/TE=4000/8.5ms, 0.55mm in-plane resolution, 2mm slice thickness, 16 slices, 3min scan time) with two different flow suppression techniques (mDIR and MSDE) were obtained separately. For each subject, bilateral arteries were reviewed. One radiologist blinded to time points, flow suppression techniques, and clinical information, measured the arterial lumen area, wall area and total vessel wall area. Results Compared to mDIR, the MSDE technique had a smaller inter-scan standard deviation (SD) in lumen (SD: 3.6 vs. 5.2 mm2, p=0.02), wall area measurements (SD: 4.5 vs. 6.4 mm2, p=0.02) and total vessel area measurement (SD: 4.4 vs. 4.9 mm2, p=0.07), and a trend towards smaller SD in total vessel area measurement (SD: 4.4 vs. 4.9 mm2, p=0.07). Conclusion The results from this study demonstrated that vessel wall imaging could quantify atherosclerotic plaque measurements more reliably with improved blood suppression technique. This relationship between flow suppression efficiency and reproducibility of plaque measurements is important as more reliable area measurements will be useful in clinical diagnosis and in serial MRI studies that monitor carotid atherosclerotic lesion progression and regression. PMID:20677277

Dong, Li; Wang, Jinnan; Yarnykh, Vasily L.; Underhill, Hunter R.; Neradilek, Moni B.; Polissar, Nayak; Hatsukami, Thomas S.; Yuan, Chun

2010-01-01

14

Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice  

PubMed Central

Background Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase which metabolizes angiotensin II (Ang II) to generate Ang-(1–7), has been shown to prevent cardiac hypertrophy and injury but the mechanism remains elusive. Irbesartan has the dual actions of angiotensin receptor blockade and peroxisome proliferator-activated receptor-? (PPAR?) activation. We hypothesized that irbesartan would exert its protective effects on ACE2 deficiency-mediated myocardial fibrosis and cardiac injury via the PPAR? signaling. Methods 10-week-old ACE2 knockout (ACE2KO; Ace2-/y) mice received daily with irbesartan (50 mg/kg) or saline for 2 weeks. The wild-type mice (Ace2+/y) were used to the normal controls. We examined changes in myocardial ultrastructure, fibrosis-related genes and pathological signaling by real-time PCR gene array, Western blotting, Masson trichrome staining and transmission electron microscope analyses, respectively. Results Compared with the Ace2+/y mice, cardiac expression of PPAR? and PPAR? were reduced in Ace2-/y mice and the myocardial collagen volume fraction (CVF) and expression of fibrosis-related genes were increased, including transforming growth factor-?1 (TGF?1), connective tissue growth factor (CTGF), collagen I and collagen III. Moreover, ACE2 deficiency triggered cardiac hypertrophy, increased myocardial fibrosis and adverse ultrastructure injury in ACE2KO hearts with higher levels of atrial natriuretic factor (ANF) and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), without affecting cardiac systolic function. Intriguingly, treatment with irbesartan significantly reversed ACE2 deficiency-mediated pathological hypertrophy and myocardial fibrosis in Ace2-/y mice linked with enhancement of plasma Ang-(1–7) level and downregulation of AT1 receptor in heart. Consistent with attenuation of myocardial fibrosis and ultrastructure injury, the myocardial CVF and levels of ANF, TGF?1, CTGF, collagen I, collagen III and phosphorylated ERK1/2 were lower, and expression of PPAR? was higher in ACE2KO mice in response to irbesartan treatment, without affecting cardiac expression of PPAR?, PPAR?, ?-myosin heavy chain, TGF?2 and fibronectin. Conclusions We conclude that irbesartan prevents ACE2 deficiency-mediated pathological hypertrophy and myocardial fibrosis in ACE2 mutant mice via activation of the PPAR? signaling and suppression of the TGF??CTGF?ERK signaling, resulting in attenuation of myocardial injury. Drugs targeting ACE2 and PPAR? represent potential candidates to prevent and treat myocardial injury and related cardiac disorders. PMID:24067190

2013-01-01

15

Differential Effects of Enalapril and Irbesartan in Experimental Papillary Necrosis  

Microsoft Academic Search

This study was undertaken to determine whether angiotensin receptor blockers are as renoprotective as angiotensin-converting enzyme inhibitors in an experimental model of chronic interstitial renal disease. Groups of rats received one of the following treatments for 1 week: (1) enalapril, (2) diltiazem, (3) a cocktail of hydralazine, reserpine, and hydrochlorothiazide, or (4) irbesartan (an AT1 antagonist). The animals were injected

Sandra L. Garber; Yelena Mirochnik; Jose A. L. Arruda; George Dunea; Leonid Slobodskoy

2001-01-01

16

Stimulation of ?7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice.  

PubMed

Atherosclerosis is a chronic inflammatory disease. It has been appreciated that vagus nerve inhibits macrophage activation via ?7 nicotinic acetylcholine receptor (nAChR), termed the cholinergic anti-inflammatory pathway. We explored the effects of AR-R17779, a selective ?7nAChR agonist, on atherosclerosis and aneurysm formation in apolipoprotein E (ApoE)-deficient mice. ApoE-deficient mice were fed a high-fat diet (HFD) and angiotensin II (Ang II) was infused by osmotic minipumps from 10-week-old for 4weeks. AR-R17779 was given in drinking water ad libitum. Oil red O staining of the aorta showed that combined loading of HFD and Ang II induced marked atherosclerosis compared with control mice fed a normal chow. Treatment with AR-R17779 significantly reduced atherosclerotic plaque area and improved survival of mice. Treatment with AR-R17779 also suppressed abdominal aortic aneurysm formation. Quantitative RT-PCR of the aorta revealed that mRNA expression levels of interleukin-1?, interleukin-6 and NOX2 were significantly decreased in AR-R17779-treated mice compared with Ang II+HFD mice. AR-R17779 treatment also reduced blood pressure and serum lipid levels. In conclusion, ?7nAChR activation attenuates atherogenesis and aortic abdominal aneurysm formation in ApoE-deficient mice possibly through an anti-inflammatory effect and reduction of blood pressure and lipid levels. Pharmacological activation of ?7nAChR may have a therapeutic potential against atherosclerotic vascular diseases through multiple mechanisms. PMID:24685818

Hashimoto, Toru; Ichiki, Toshihiro; Watanabe, Aya; Hurt-Camejo, Eva; Michaëlsson, Erik; Ikeda, Jiro; Inoue, Eriko; Matsuura, Hirohide; Tokunou, Tomotake; Kitamoto, Shiro; Sunagawa, Kenji

2014-01-01

17

Dose-Related Antihypertensive Effects of Irbesartan in Patients With Mild-to-Moderate Hypertension  

Microsoft Academic Search

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either

James L. Pool; Robert M. Guthrie; Thomas W. Littlejohn; Philip Raskin; Alexander M. M. Shephard; Michael A. Weber; Matthew R. Weir; Thomas W. Wilson; James Wright; Kenneth B. Kassler-Taub; Richard A. Reeves

1998-01-01

18

Differential effects of enalapril and irbesartan in experimental papillary necrosis.  

PubMed

This study was undertaken to determine whether angiotensin receptor blockers are as renoprotective as angiotensin-converting enzyme inhibitors in an experimental model of chronic interstitial renal disease. Groups of rats received one of the following treatments for 1 week: (1) enalapril, (2) diltiazem, (3) a cocktail of hydralazine, reserpine, and hydrochlorothiazide, or (4) irbesartan (an AT1 antagonist). The animals were injected with bromoethylamine (200 mg/kg), and antihypertensive treatment continued for 1 month. All drugs were effective in lowering the mean arterial pressure. The bromoethylamine-treated rats developed albuminuria and sustained a 40-50% decrease in creatinine clearance. Enalapril and irbesartan reduced albuminuria, but only enalapril partially prevented the decline in creatinine clearance and lowered the number of ED-1-positive cells. Diltiazem and cocktail had no effect on proteinuria, creatinine clearance, or ED-1 cells. In this experimental model, the effects of enalapril and irbesartan were not identical. Both drugs reduced proteinuria, but enalapril was more effective in protecting the renal function. The fact that the AT1 antagonist protected against albuminuria but did not affect the clearance of creatinine implies that the results seen with angiotensin-converting enzyme inhibition may be in part due to an effect on angiotensin II via AT2 receptor blockade or through an effect on bradykinin. PMID:11174005

Garber, S L; Mirochnik, Y; Arruda, J A; Dunea, G; Slobodskoy, L

2001-01-01

19

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction  

SciTech Connect

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 a 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.

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

20

Effect of ?-cyclodextrin on solubilization and complexation of irbesartan: Influence of pH and excipients.  

PubMed

In effort to prepare an eye drop formulation of irbesartan, the effect of ?-cyclodextrin complexation on irbesartan solubilization in aqueous solutions was investigated. The optimum cyclodextrin concentration for formation of irbesartan/cyclodextrin inclusion complex was found to be 10% (w/v) and the solubility of ionized irbesartan/?-cyclodextrin complex (at pH 7.2) was shown to be three fold greater than that of the unionized complex (at pH 4.3). The irbesartan flux through semipermeable membranes increased with increasing ?-cyclodextrin concentration at both pH values. However, the ionized complex displayed decrease in the drug permeation coefficient with increasing cyclodextrin concentration. The effect of four pharmaceutical excipients on the cyclodextrin solubilization was investigated. EDTA, hydroxypropyl methylcellulose, and tyloxapol increased complexation efficiency of ?-cyclodextrin while benzalkonium chloride had negligible effect. The largest solubilization was observed in the eye drop vehicle that contained all four excipients in addition to ?-cyclodextrin. Dynamic light scattering measurements disclosed that excipients had impact on size of complex aggregates and consequently on the drug flux through the semipermeable membranes. Complex of irbesartan/?-cyclodextrin was characterized by FT-IR, (1)H NMR, XRPD, and TEM techniques. PMID:25128698

Muankaew, Chutimon; Jansook, Phatsawee; Stefánsson, Einar; Loftsson, Thorsteinn

2014-10-20

21

Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.  

PubMed

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

2013-01-01

22

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke  

PubMed Central

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

2013-01-01

23

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by liquid chromatography  

Microsoft Academic Search

A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the antihypertensive drugs, irbesartan and hydrochlorothiazide is described. Good chromatographic separation was achieved using a Supelcocil C18 (5 ?m, 15 cm×4.6 mm) column and a mobile phase consisting of 10 mM potassium dihydrogen phosphate:methanol:acetonitrile (5:80:15 v\\/v\\/v) (pH:2.5) while at a flow-rate of 1.0 ml min?1. Irbesartan and hydrochlorothiazide

Nevin Erk

2003-01-01

24

Regulatory T cells and Atherosclerosis  

PubMed Central

Atherosclerosis is a chronic autoimmune inflammatory disease. The involvement of both innate and adaptive immune responses in the pathogenesis of the disease has been well recognized. Tregs are an essential part of the immune system and have indispensable functions in maintaining immune system homeostasis, mediating peripheral tolerance, preventing autoimmune diseases, and suppressing inflammatory and proatherogenic immune response. Tregs carry out their immunosuppressive functions via several mechansims. One of the well-documented suppressive mechanisms of Tregs is the secretion of anti-inflammatory cytokines including IL-10, TGF-?, and IL-35. Studies have found that IL-10 and TGF-? have atheroprotective properties. In addition, Tregs can suppress the activity of proatherogenic effector T cells, suggesting an atheroprotective role. In fact, fewer Tregs are found in atherogenic ApoE?/? mice comparing to wild-type mice, suggesting an uncontrolled balance between weakened Tregs and effector T cells in atherogenesis. Some clinical studies of autoimmune diseases also suggest that decreased Tregs numbers are associated with increased disease activity. The importance of Tregs in many autoimmune diseases and experimental atherosclerosis has been established in in vivo and in vitro studies. However, the roles of Tregs in atherosclerosis in the clinical setting remains to be further characterized. PMID:23997979

Pastrana, Jahaira Lopez; Sha, Xiaojin; Virtue, Anthony; Mai, Jietang; Cueto, Ramon; Lee, In Ae; Wang, Hong; Yang, Xiao-feng

2013-01-01

25

Short and long term effects of irbesartan in normotensives with exaggerated blood pressure response during exercise  

Microsoft Academic Search

Normotensives with exaggerated blood pressure response during exercise have impaired test parameters associated with autonomic nervous activity. We studied the short and long term effects of the angiotensin receptor blocker irbesartan on these parameters.48 subjects(36 male,12 female, mean age 58,42 ± 11,29yrs)-group A- free from known cardiovascular diseases and negative for myocardial ischemia, undergoing exercise testing for various reasons, with

Ilias Zarkos; Irini Vrana; Eleftherios Thireos; Nearchos Nearchou; Gerasimos Livieratos; Aikaterini Mitropoulou; Christos Tolis; Vasilis Tolis

2005-01-01

26

Bioequivalence study of two oral formulations of irbesartan 300?mg in healthy volunteers.  

PubMed

A bioequivalence study of 2 irbesartan (CAS 138402-11-6) film-coated tablet formulations was carried out in 40 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 96?h following drug administration. Plasma concentrations of irbesartan were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference). tmax was analysed nonparametrically. The 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t (98.06-109.48%, point estimator 103.61%) and Cmax (88.93-100.87%, point estimator 94.72%) were within the bioequivalence acceptance range of 80-125%. According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that test formulation of irbesartan 300?mg film-coated tablet is bioequivalent to the reference formulation. Overall, it was judged that the study was conducted with a good tolerance of the subjects to both study drugs. PMID:24048950

Cánovas, M; Cabré, F; Polonio, F

2014-01-01

27

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies.  

PubMed

A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C(18) column (50mmx4mm, 3microm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide, 427-->175 for irbesartan. Linearity was demonstrated over the concentration range 0.06-6.00microg/mL for irbesartan and 1.00-112.00ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300mg) with hydrochlorothiazide (12.5mg) tablet in healthy volunteers (N=36). PMID:20004542

Tutunji, Lara F; Tutunji, Maha F; Alzoubi, Mamoun I; Khabbas, Manal H; Arida, Adi I

2010-03-11

28

Vinpocetine attenuates lipid accumulation and atherosclerosis formation  

SciTech Connect

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)] [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

29

Atherosclerosis Prevention in Youth  

PubMed Central

Atherosclerosis-associated circulatory disturbance is one of the most important global issues. In patients with atherosclerosis, eccentric intimal thickening and lipid deposition progress over a long period (at least 20 to 30 years). On the other hand, in patients with atherosclerosis-associated circulatory disturbance represented by myocardial infarction, the direct cause of death is thrombus formation rather than marked stenosis; wall destruction may lead to a fatal outcome. In the future, atherosclerosis susceptibility, that is, intrinsic genes, should be investigated. PMID:23641261

2012-01-01

30

Dendritic cells in atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disease with activation of both the innate and adaptive arms of the immune system. Dendritic cells (DCs) are potent activators of adaptive immunity and have been identified in the normal arterial wall and within atherosclerotic lesions. Recent evidence points to a functional role for DCs in all stages of atherosclerosis because of their myriad functions including lipid uptake, antigen presentation, efferocytosis, and inflammation resolution. Moreover, DC-based vaccination strategies are currently being developed for the treatment of atherosclerosis. This review will focus on the current evidence as well as the proposed roles for DCs in the pathogenesis of atherosclerosis and discuss future therapeutic strategies. PMID:24196454

Subramanian, Manikandan; Tabas, Ira

2014-01-01

31

Dendritic cells in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease with activation of both the innate and adaptive arms of the immune system. Dendritic cells (DCs) are potent activators of adaptive immunity and have been identified in the normal arterial wall and within atherosclerotic lesions. Recent evidence points to a functional role for DCs in all stages of atherosclerosis because of their myriad functions including lipid uptake, antigen presentation, efferocytosis, and inflammation resolution. Moreover, DC-based vaccination strategies are currently being developed for the treatment of atherosclerosis. This review will focus on the current evidence as well as the proposed roles for DCs in the pathogenesis of atherosclerosis and discuss future therapeutic strategies. PMID:24196454

Tabas, Ira

2013-01-01

32

Chlamydia pneumoniae and atherosclerosis  

Microsoft Academic Search

OBJECTIVETo review the literature for evidence that chronic infection withChlamydia pneumoniae is associated with atherosclerosis and acute coronary syndromes.DATA SOURCESmedline and Institute of Science and Information bibliographic databases were searched at the end of September 1998. Indexing terms used were chlamydi*, heart, coronary, and atherosclerosis. Serological and pathological studies published as papers in any language since 1988 or abstracts since

Y-K Wong; P J Gallagher; M E Ward

1999-01-01

33

[AII antagonists (candesartan and irbesartan) in the treatment of cardiovascular diseases].  

PubMed

Treatment of hypertension with angiotensin II receptor antagonists (AIIA) was first limited to diabetics and patients with microalbuminuria. So far, results of several large clinical trials with AIIAs were published, confirming significant renoprotective effect of these agents compared to placebo (RENAAL and IRMA), amlodipin (MARVAL and IDNT) and a combination of ACEI and AIIA (CALM). In 2002, results of 2 large comparator studies in hypertension were published: LIFE - Losartan Intervention For Endpoints and SCOPE - the Study on COgnition and Prognosis in Elderly hypertensives. In 2003, a series of the CHARM studies involving patients with heart failure were published and, from than, AIIA have been used as an alternative to ACEI or in a combination with ACEI. MOSES study - Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention - results were published in 2005 and ONTARGET study, focusing on secondary prevention of ischemic heart disease, was published in 2008. The CORD study - Comparison of recommended doses - and the ACTIVE I study (AF Clopidogrel Trial with Irbesartan for prevention of Vascular Events) were published in 2009. Candesartan was used in the CALM, SCOPE, RESOLVED and CHARM studies, irbesartan in the IRMA, IDNT and ACTIVE I. PMID:23121062

Spinar, J; Vítovec, J

2012-10-01

34

Vinpocetine attenuates lipid accumulation and atherosclerosis formation.  

PubMed

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. PMID:23583194

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-05-10

35

Vinpocetine Attenuates Lipid Accumulation and Atherosclerosis Formation  

PubMed Central

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis PMID:23583194

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

36

Animal models of atherosclerosis.  

PubMed

In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

2014-05-16

37

Immunological aspects of atherosclerosis.  

PubMed

Atherosclerosis is a complex chronic inflammatory and metabolic disease that involves the collaboration of several cellular components of the immune system and results in thickening of the arterial wall. Atherosclerosis is also the primary cause of coronary artery and cerebrovascular diseases. A multitude of immune cell subsets, soluble molecules such as chemokines and cytokines, and circulating lipids play pivotal roles in atherosclerosis development. In this review, we highlight the role of the immune system in the course of atherosclerotic disease development and discuss the mechanisms involved. PMID:24212253

Garrido-Urbani, S; Meguenani, M; Montecucco, F; Imhof, B A

2014-01-01

38

Cytomegalovirus and atherosclerosis.  

PubMed

An avian herpesvirus is known to cause atherosclerosis in chickens. The same virus can induce a proliferative disease, malignant lymphoma, suggesting that this agent may also have transforming potential and thus stimulate the proliferation of arterial smooth muscle cells, a prominent feature of atherogenesis. The evidence for involvement of cytomegalovirus (CMV), a member of the human herpesvirus family, in atherosclerosis is much more circumstantial. The finding of CMV antigen and nucleic acid sequences in arterial smooth muscle cells of humans suggests that viral infection of the arterial wall may be common in the general population, including patients with severe atherosclerosis. In seroepidemiological studies, high levels of CMV antibodies were found to be associated with clinically manifest atherosclerotic disease, suggesting that a periodically activated latent infection or a continuously active infection is present in patients with atherosclerosis. Since the viral genome but not infectious virus is found in arterial cells, the artery itself may be the site of CMV latency. Of particular significance is the recent finding that heart transplant recipients, who are immunosuppressed, and who are also actively infected with CMV, are prone to develop accelerated atherosclerosis in the transplanted organ. Although suggestive, these observations by themselves do not demonstrate that viruses have a role in the pathogenesis of atherosclerosis, but they support a working hypothesis of the steps involved. PMID:8131785

Melnick, J L; Adam, E; Debakey, M E

1993-12-01

39

Irbesartan attenuates ischemic brain damage by inhibition of MCP-1\\/CCR2 signaling pathway beyond AT 1 receptor blockade  

Microsoft Academic Search

Angiotensin II type 1 (AT1) receptor blockers (ARBs) are known to prevent the onset of stroke and to attenuate neural damage. Additional beneficial effects of ARBs, independent of AT1 receptor blockade, have been highlighted. Irbesartan is reported to act as an antagonist of the monocyte chemoattractant protein-1 (MCP-1) receptor, C–C chemokine receptor 2 (CCR2), due to its molecular structure. We

Kana Tsukuda; Masaki Mogi; Jun Iwanami; Li-Juan Min; Fei Jing; Kousei Oshima; Masatsugu Horiuchi

2011-01-01

40

Macrophage Autophagy in Atherosclerosis  

PubMed Central

Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. PMID:23401644

Maiuri, Maria Chiara; Grassia, Gianluca; Platt, Andrew M.; Carnuccio, Rosa; Ialenti, Armando; Maffia, Pasquale

2013-01-01

41

The UPR in atherosclerosis  

PubMed Central

Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1? (IRE1?), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1? pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of prelesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1? activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information for therapeutic advances. PMID:23553213

Zhou, Alex X.; Tabas, Ira

2014-01-01

42

Imaging of Atherosclerosis  

PubMed Central

It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis. PMID:21226610

Owen, D.R.J.; Lindsay, A.C.; Choudhury, R.P.; Fayad, Z.A.

2014-01-01

43

Genes Involved in Atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.

Johanna Laukkanen; Seppo Ylä-Herttuala

2002-01-01

44

Intercellular Communication in Atherosclerosis  

NSDL National Science Digital Library

Cell-to-cell communication is a process necessary for physiological tissue homeostasis and appears often altered during disease. Gap junction channels, formed by connexins, allow the direct intercellular communication between adjacent cells. After a brief review of the pathophysiology of atherosclerosis, we will discuss the role of connexins throughout the different stages of the disease.

Laurent Burnier (University of Lausanne); Pierre Fontana (University of Geneva); Anne Angelillo-Scherrer (University of Lausanne)

2009-02-01

45

Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with the angiotensin receptor blocker irbesartan: a randomized controlled trial.  

PubMed

This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone. PMID:23519822

Qiu, HongYu; Fu, Ping; Fan, WenXing; Zuo, Chuan; Feng, Ping; Shi, Peng; Cao, Lina; Liu, Fang; Zhou, Li; Chen, Feng; Zhong, Hui; Gou, ZhongPing; Liang, YaPing; Shi, Mei

2014-01-01

46

Macrophage death and defective inflammation resolution in atherosclerosis  

Microsoft Academic Search

A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can

Ira Tabas

2009-01-01

47

Shear Stress and Atherosclerosis  

PubMed Central

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flow-dependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis. PMID:24781409

Heo, Kyung-Sun; Fujiwara, Keigi; Abe, Jun-ichi

2014-01-01

48

HPLC method with monolithic column for simultaneous determination of irbesartan and hydrochlorothiazide in tablets.  

PubMed

A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith(®) Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min(-1). The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ? 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL(-1). The limits of detection were 2.34 and 0.03 ng mL(-1) for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run-time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT. PMID:24914719

Alanazi, Amer M; Abdelhameed, Ali S; Khalil, Nasr Y; Khan, Azmat A; Darwish, Ibrahim A

2014-06-01

49

Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan  

PubMed Central

Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor® EL (43.33%), Carbitol® (21.67%) and Capryol® 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286

Patel, Jaydeep; Patel, Anjali; Raval, Mihir; Sheth, Navin

2011-01-01

50

Vascular Endothelium and Atherosclerosis  

Microsoft Academic Search

Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and\\u000a smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The\\u000a homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including\\u000a the appropriate regulation of blood flow, a basal

P. Libby; M. Aikawa; M. K. Jain

51

Immunization for atherosclerosis  

Microsoft Academic Search

This review summarizes experimental findings that highlight the complex roles of the immune system in atherogenesis. Immune\\u000a activation can have either proatherogenic or atheroprotective effects. Immune-modulation therapy via an active or passive\\u000a immunization strategy aims to exploit the atheroprotective aspects of the immune system to modulate atherosclerosis. Several\\u000a experimental studies have demonstrated that such an approach is feasible and effective,

Kuang-Yuh Chyu; Jan Nilsson; Prediman K. Shah

2007-01-01

52

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism  

SciTech Connect

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor {beta} (LXR{beta}) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXR{beta} activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXR{beta} and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: > Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. > Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs-CRP. > Arsenic exposure and high cholesterol diet early in life suppress CEPT-1 and LXR? > Arsenic may induce atherosclerosis by modifying reverse cholesterol transport. > Prevent arsenic exposure in early life is important to decreasing atherosclerosis.

Cheng, Tain-Junn [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Occupational Medicine, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan (China); Department of Occupational Safety, College of Environment, Chia Nan University of Pharmacy and Science, 60, Sec. 1, Erh-Jen Road, Jen-Te, Tainan 711, Taiwan (China); Chuu, Jiunn-Jye [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Chang, Chia-Yu [Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Tsai, Wan-Chen; Chen, Kuan-Jung [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Guo, How-Ran, E-mail: hrguo@mail.ncku.edu.tw [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Sustainable Environment Research Center, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Center for Occupational and Environmental Health and Preventive Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China)

2011-10-15

53

Macrophage phenotypes in atherosclerosis.  

PubMed

Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype. PMID:25319333

Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

2014-11-01

54

Curing atherosclerosis should be the next major cardiovascular prevention goal.  

PubMed

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in developed and developing countries. Despite decades of effort, unhealthy lifestyle habits and ASCVD risk factor levels remain high and are increasing in many population groups. A new approach to ASCVD prevention is needed. Multiple lines of evidence from animal and human studies suggest that atherosclerosis regression and normalization of vessel function can occur when low-density lipoprotein cholesterol (LDL-C) lowering occurs early in the course of atherosclerosis or when very aggressive LDL-C lowering occurs somewhat later. We propose a new paradigm focused on curing atherosclerosis early in the course of the disease. An approach that resets the vascular aging clock composed of initial regression therapy followed by periodic retreatment to suppress atherosclerosis development may be possible, with the ultimate goal of preventing subsequent ASCVD events. Proof-of-concept studies are needed to determine: 1) the optimal age and/or extent of atherosclerosis for intervention and LDL-C-lowering therapy; 2) the intensity and duration of therapy for inducing atherosclerosis regression; and 3) documenting the normalization of vascular function. Ultimately, this new paradigm will need to be evaluated in ASCVD outcomes trials. PMID:24814489

Robinson, Jennifer G; Gidding, Samuel S

2014-07-01

55

The genetic basis of atherosclerosis  

Microsoft Academic Search

Atherogenesis is a complex process that involves the contributions of several pathophysiological subsystems. The dissection\\u000a of the genetic component of atherosclerosis has become possible using current molecular technologies and analytical methods.\\u000a Genetic factors are considered to determine the limits under which atherosclerosis develops and environmental factors are\\u000a considered to position an individual’s risk within these limits. Atherosclerosis proceeds through a

R. A. Hegele

1997-01-01

56

Endothelial progenitor cells in atherosclerosis  

PubMed Central

Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs’ population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis. PMID:22652782

Du, Fuyong; Zhou, Jun; Gong, Ren; Huang, Xiao; Pansuria, Meghana; Virtue, Anthony; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng

2012-01-01

57

Cardiac and Renal Protective Effects of Irbesartan via Peroxisome Proliferator-Activated Receptor?-Hepatocyte Growth Factor Pathway Independent of Angiotensin II Type 1a Receptor Blockade in Mouse Model of Salt-Sensitive Hypertension  

PubMed Central

Background “Aldosterone breakthrough” observed in patients receiving long?term treatment with angiotensin blockade is strongly associated with increased risk of left ventricular hypertrophy, poor exercise capacity, refractory proteinuria, and declining glomerular filtration rate through the profibrotic actions of aldosterone. To overcome aldosterone breakthrough, we examined the additional organ?protective actions of irbesartan, because irbesartan is an angiotensin II type 1 receptor (AT1R) blocker (ARB) with peroxisome proliferator?activated receptor (PPAR)? agonistic effects, which mediate organ?protective effects independent of AT1R blockade. In this study, we examined the organ?protective effects of irbesartan in a salt?sensitive hypertension model using AT1aR knockout mice. Methods and Results Aldosterone and 1% NaCl treatment resulted in a significant increase in severe cardiac and renal fibrosis. Irbesartan, but not losartan, significantly reduced renal fibrosis, glomerular injury through inhibition of macrophage infiltration, epithelial–mesenchymal transition, and oxidative stress. Similarly, cardiac fibrosis and myocyte hypertrophy were decreased by irbesartan, but not losartan, treatment, associated with a significant reduction in oxidative stress. Importantly, anti–hepatocyte growth factor (HGF) neutralizing antibody and a PPAR? antagonist (GW9662) attenuated these organ?protective effects of irbesartan. HGF protein level was increased by irbesartan, especially in the kidney and heart, while GW9662 treatment inhibited the increase in HGF level. Conclusions In this study, we showed that irbesartan, which has not only AT1aR?blocking effects, but also PPAR? agonistic effects accompanied by HGF expression, inhibited organ damage by aldosterone and salt treatment. Second?generation ARBs such as irbesartan, which has the dual actions of AT1R blockade and PPAR? activation, may have clinical value for the treatment of hypertensive patients with aldosterone breakthrough. PMID:23608606

Kusunoki, Hiroshi; Taniyama, Yoshiaki; Rakugi, Hiromi; Morishita, Ryuichi

2013-01-01

58

Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats.  

PubMed

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T(1) (AT(1)) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP. PMID:20446791

Kanter, Mehmet; Sen, Saniye; Donmez, Salim; Aktas, Cevat; Ustundag, Sedat; Erboga, Mustafa

2010-05-01

59

Molecular biology of atherosclerosis.  

PubMed

At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-? and related family members leading to activation of NF-?B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world. PMID:23899566

Hopkins, Paul N

2013-07-01

60

Macrophage function in atherosclerosis  

PubMed Central

Cation channels of the Transient Receptor Potential Canonical (TRPC) group, which belong to the larger TRP superfamily of channel proteins, are critical players in cardiovascular disease. Recent studies underscored a role of TRPC3 in macrophage survival and efferocytosis, two critical events in atherosclerosis lesion development. Also, other members of the TRP channel superfamily are found expressed in monocytes/macrophages, where they participate in processes that might be of significance to atherogenesis. These observations set a framework for future studies aimed at defining the ultimate functions not only of TRPC3, but probably other TRP channels, in macrophage biology. The purpose of this manuscript is to provide a timely revision of existing evidence on the role of members of the TRP channel superfamily, in particular TRPCs, in macrophages and discuss it in the context of the macrophage’s function in atherogenesis. PMID:22909953

Tano, Jean-Yves K.; Lee, Robert H.; Vazquez, Guillermo

2012-01-01

61

MicroRNAs and atherosclerosis  

PubMed Central

MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernandez-Hernando, Carlos

2014-01-01

62

Novel immune signals and atherosclerosis.  

PubMed

Atherosclerosis underlies coronary artery disease (CAD) and cerebrovascular disease, which are the most common forms of life-threatening cardiovascular disorders. To minimize the risk of atherosclerotic complications, primary and secondary prevention strategies seek to control risk factors. Reducing low-density lipoprotein (LDL) cholesterol through lipid-lowering drugs, such as statins, in particular yields a proportional decrease in cardiovascular disease risk. Atherosclerosis is considered to be a complex chronic inflammatory process triggered by cardiovascular risk factors which cause endothelial dysfunction and inflammatory cell infiltration within the artery wall. In this review, we summarize the current understanding of the underling molecular mechanisms of the immune signals in the development and progression of atherosclerosis. Among various molecular mechanisms, toll like receptors (TLRs) are potent proinflammatory cytokines that operate to induce inflammation play an important role in the pathogenesis of atherosclerosis. Moreover, we discuss current knowledge regarding monocyte/macrophage biology that contributes to the progression of atherosclerosis, including macrophage polarization and heterogeneity. Understanding the molecular mechanisms in conjunction with orchestration of monocyte/macrophage biology should provide a basis for novel treatment strategies to prevent the development and progression of atherosclerosis. PMID:22864646

Iwata, Hiroshi; Nagai, Ryozo

2012-10-01

63

Atherosclerosis: Prevention by Agents not Affecting Abnormal Levels of Blood Lipids  

Microsoft Academic Search

Diet-induced atherosclerosis in macaque monkeys was suppressed by anticalcifying agents without changing abnormal levels of blood cholesterol and lipoprotein. The agents included inhibitors of arterial calcium deposition (diphosphonates) and a calcium ion antagonist (lanthanum). The study suggests that regulation of calcium flux and extracellular deposition in arteries may offer new principles of treatment for cardiovascular disease.

Dieter M. Kramsch; Anita J. Aspen; Lynn J. Rozler

1981-01-01

64

Dietary fat and experimental atherosclerosis.  

PubMed

This paper reviews studies relating to the effects of fat unsaturation and fatty acid composition on the development of experimental atherosclerosis in rabbits. The results derived from the feeding of various fats are similar whether one feeds cholesterol or an atherogenic, cholesterol-free semipurified diet. In general, the severity of atherosclerosis is inversely related to the level of fat unsaturation. Two exceptions are cocoa butter which is much less atherogenic than expected, most probably due to its high content of stearic acid, and peanut oil, while relatively unsaturated, is surprisingly atherogenic for rats, rabbits and monkeys. This latter effect is not related to the level (6%) of long-chain saturated fatty acids (arachidic, behenic, lignoceric) present in peanut oil, but rather to its triglyceride structure. Randomization of peanut oil, which modifies its triglyceride structure, significantly reduces its atherogenicity. PMID:1955294

Kritchevsky, D

1991-01-01

65

Bioequivalence studies for 2 different strengths of irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25?mg and 300/12.5?mg film-coated tablets.  

PubMed

Two bioequivalence studies of irbesartan (CAS 138402-11-6) and hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5?mg and 300/25?mg strengths were carried out in order to assess the bioequivalence of these film-coated tablet formulations in comparison with the marketed reference formulations.Both studies were performed with 30 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. In each study, test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 72?h following drug administration in case of irbesartan and up to 24?h in case of hydrochlorothiazide. Plasma concentrations of both analytes were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference).For both studies, the 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t [(irbesartan: 300/12.5?mgstrength: 95.33-111.74%. 300/25?mg strength: 91.27-103.93%) (hydrochlorothiazide: 300/12.5?mg strength: 99.63-107.50%. 300/25?mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5?mg strength: 98.73-115.03%. 300/25?mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5?mg strength: 97.34-112.06%. 300/25?mg strength: 93.29-106.38%)] were within the bio-equivalence acceptance range of 80-125%.According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that both test formulations are bioequivalent to the corresponding reference formulations. Overall, it was judged that both studies were conducted with a good tolerance of the subjects to study drugs. PMID:24105103

Cánovas, M; Cabré, F; Polonio, F

2014-05-01

66

Aspirin Improves Endothelial Dysfunction in Atherosclerosis  

Microsoft Academic Search

Background—The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. We hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action can be reversed by aspirin. Methods and Results—In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested

Syed Husain; Neil P. Andrews; David Mulcahy; Julio A. Panza; Arshed A. Quyyumi

2010-01-01

67

[Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].  

PubMed

Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events. PMID:25266094

Kohara, Katsuhiko

2014-10-01

68

Multi-Ethnic Study of Atherosclerosis (MESA)  

ClinicalTrials.gov

Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

2012-04-26

69

Cathepsin G activity lowers plasma LDL and reduces atherosclerosis.  

PubMed

Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3months. When mice consume this diet for 6months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r=-0.535, P<0.0001) and LDL cholesterol (r=-0.559, P<0.0001), but not with HDL cholesterol (P=0.901) or triglycerides (P=0.186). Such inverse correlations with total cholesterol (r=-0.504, P<0.0001) and LDL cholesterol (r=-0.502, P<0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides. PMID:25092171

Wang, Jing; Sjöberg, Sara; Tang, Ting-Ting; Oörni, Katariina; Wu, Wenxue; Liu, Conglin; Secco, Blandine; Tia, Viviane; Sukhova, Galina K; Fernandes, Cleverson; Lesner, Adam; Kovanen, Petri T; Libby, Peter; Cheng, Xiang; Shi, Guo-Ping

2014-11-01

70

Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients  

Microsoft Academic Search

OBJECTIVES: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor

Ulrich Kintscher; Peter Bramlage; W Dieter Paar; Martin Thoenes; Thomas Unger

2007-01-01

71

A validated stability-indicating liquid chromatographic method for determination of process related impurities and degradation behavior of Irbesartan in solid oral dosage.  

PubMed

The present work describes the development and validation of a stability-indicating RP-HPLC method for the estimation of degradation and process related impurities of Irbesartan, namely Impurity-1, Impurity-2, Impurity-3 and Impurity-4. The developed LC method was validated with respect to specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The chromatographic separation was achieved on Hypersil Octadecylsilyl (4.6 mm × 150 mm, 3 ?m) column by using mobile phase containing a gradient mixture of solvent A (0.55% v/v ortho-phosphoric acid, pH adjusted to 3.2 with triethyl amine) and B (95:5 v/v mixture of acetonitrile and solvent A) at a flow rate of 1.2 mL/min. The detection was carried out at a wavelength of 220 nm. During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The method is stability-indicating in nature and can be used for routine analysis of production samples and to check the stability of the Irbesartan HCl tablets. PMID:24695518

Goswami, Nishant

2014-01-01

72

A validated stability-indicating liquid chromatographic method for determination of process related impurities and degradation behavior of Irbesartan in solid oral dosage  

PubMed Central

The present work describes the development and validation of a stability-indicating RP-HPLC method for the estimation of degradation and process related impurities of Irbesartan, namely Impurity-1, Impurity-2, Impurity-3 and Impurity-4. The developed LC method was validated with respect to specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The chromatographic separation was achieved on Hypersil Octadecylsilyl (4.6 mm × 150 mm, 3 ?m) column by using mobile phase containing a gradient mixture of solvent A (0.55% v/v ortho-phosphoric acid, pH adjusted to 3.2 with triethyl amine) and B (95:5 v/v mixture of acetonitrile and solvent A) at a flow rate of 1.2 mL/min. The detection was carried out at a wavelength of 220 nm. During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The method is stability-indicating in nature and can be used for routine analysis of production samples and to check the stability of the Irbesartan HCl tablets. PMID:24695518

Goswami, Nishant

2014-01-01

73

Therapeutic approaches to drug targets in atherosclerosis.  

PubMed

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPAR?, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

Jamkhande, Prasad G; Chandak, Prakash G; Dhawale, Shashikant C; Barde, Sonal R; Tidke, Priti S; Sakhare, Ram S

2014-07-01

74

Therapeutic approaches to drug targets in atherosclerosis  

PubMed Central

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPAR?, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

Jamkhande, Prasad G.; Chandak, Prakash G.; Dhawale, Shashikant C.; Barde, Sonal R.; Tidke, Priti S.; Sakhare, Ram S.

2013-01-01

75

Quantification of carotid vessel atherosclerosis  

NASA Astrophysics Data System (ADS)

Atherosclerosis is characterized by the development of plaques in the arterial wall, which ultimately leads to heart attacks and stroke. 3D ultrasound (US) has been used to screen patients' carotid arteries. Plaque measurements obtained from these images may aid in the management and monitoring of patients, and in evaluating the effect of new treatment options. Different types of measures for ultrasound phenotypes of atherosclerosis have been proposed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US images obtained at two different time points. We evaluated our technique using manual segmentations of the wall and lumen of the carotid artery from images acquired in two US scanning sessions. To incorporate the effect of intraobserver variability in our evaluation, manual segmentation was performed five times each for the arterial wall and lumen. From this set of five segmentations, the mean wall and lumen surfaces were reconstructed, with the standard deviation at each point mapped onto the surfaces. A correspondence map between the mean wall and lumen surfaces was then established, and the thickness of the atherosclerotic plaque at each point in the vessel was estimated to be the distance between each correspondence pairs. The two-sample Student's t-test was used to judge whether the difference between the thickness values at each pair corresponding points of the arteries in the two 3D US images was statistically significant.

Chiu, Bernard; Egger, Micaela; Spence, J. D.; Parraga, Grace; Fenster, Aaron

2006-03-01

76

Leukotrienes as Modifiers of Preclinical Atherosclerosis?  

PubMed Central

Preclinical atherosclerosis represents a crucial period associated with several pathophysiological reactions in the vascular wall. Failure to diagnose preclinical atherosclerosis at this stage misses a major opportunity to prevent the long-term consequences of this disease. Surrogate biological and structural vascular markers are available to determine the presence and the extension of preclinical vascular injury in the general population. Examples of surrogate markers are carotid intima media thickness and biomarkers including high-sensitivity C-reactive protein, cell adhesion molecules and matrix metalloproteinases, and leukotrienes. Recently, leukotrienes have been implicated as mediators, biomarkers, and possible therapeutic targets in the context of subclinical atherosclerosis. The aim of this short paper is to focus on the relation between preclinical atherosclerosis and leukotrienes, with particular attention to the recent development on the use of leukotriene modifiers in the treatment of atherosclerosis. PMID:22645425

Riccioni, Graziano; Back, Magnus

2012-01-01

77

Atherosclerosis  

MedlinePLUS

... heart attack. Plaque also can form in the heart's smallest arteries. This disease is called coronary microvascular disease (MVD). In coronary MVD, plaque doesn't cause blockages in the arteries as it does in CHD. Carotid Artery Disease Carotid (ka-ROT-id) artery disease occurs if plaque builds up ...

78

Atherosclerosis  

MedlinePLUS

... what causes it isn't known, but some theories have been proposed. Many scientists believe plaque begins ... legs. Because of the damage, fats, cholesterol, platelets, cellular debris and calcium accumulate over time in the ...

79

Vitamin D Deficiency Induces High Blood Pressure and Accelerates Atherosclerosis in Mice  

PubMed Central

Multiple epidemiological studies link vitamin D deficiency to increased cardiovascular disease (CVD), but causality and possible mechanisms underlying these associations are not established. To clarify the role of vitamin D-deficiency in CVD in vivo, we generated mouse models of diet-induced vitamin D deficiency in two backgrounds (LDL receptor- and ApoE-null mice) that resemble humans with diet-induced hypertension and atherosclerosis. Mice were fed vitamin D-deficient or -sufficient chow for 6 weeks and then switched to high fat (HF) vitamin D-deficient or –sufficient diet for 8–10 weeks. Mice with diet-induced vitamin D deficiency showed increased systolic and diastolic blood pressure, high plasma renin, and decreased urinary sodium excretion. Hypertension was reversed and renin was suppressed by returning chow-fed vitamin D-deficient mice to vitamin D-sufficient chow diet for 6 weeks. On a HF diet, vitamin D-deficient mice had ?2-fold greater atherosclerosis in the aortic arch and ?2–8-fold greater atherosclerosis in the thoracic and abdominal aorta compared to vitamin D-sufficient mice. In the aortic root, HF-fed vitamin D-deficient mice had increased macrophage infiltration with increased fat accumulation and endoplasmic reticulum (ER) stress activation, but a lower prevalence of the M1 macrophage phenotype within atherosclerotic plaques. Similarly, peritoneal macrophages from vitamin D-deficient mice displayed an M2-predominant phenotype with increased foam cell formation and ER stress. Treatment of vitamin D-deficient mice with the ER stress reliever PBA during HF feeding suppressed atherosclerosis, decreased peritoneal macrophage foam cell formation, and downregulated ER stress proteins without changing blood pressure. Thus, we suggest that vitamin D deficiency activates both the renin angiotensin system and macrophage ER stress to contribute to the development of hypertension and accelerated atherosclerosis, highlighting vitamin D replacement as a potential therapy to reduce blood pressure and atherosclerosis. PMID:23349943

Oh, Jisu; Riek, Amy E.; Chin, Kathleen; Garcia, Miguel; Bernal-Mizrachi, Carlos

2013-01-01

80

The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression  

PubMed Central

Aim: The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker. Methods: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA. Results: In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure. Conclusion: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN. PMID:19169272

Chen, Hai-bing; Lu, Jun-xi; Li, Qing; Bao, Yu-qian; Tang, Jun-ling; Lu, Hui-juan; Xiang, Kun-san; Jia, Wei-ping

2009-01-01

81

LXR signaling pathways and atherosclerosis  

PubMed Central

First discovered as orphan receptors, liver X receptors (LXRs) were subsequently identified as the nuclear receptor target of the cholesterol metabolites, oxysterols.1 There are 2 LXR receptors encoded by distinct genes: LXR? is most highly expressed in the liver, adipose, kidney, adrenal tissues and macrophages, and LXR? is ubiquitously expressed. Despite differential tissue distribution, these isoforms have 78% homology in their ligand-binding domain and appear to respond to the same endogenous ligands. Work over the past 10 years has shown that the LXR pathway regulates lipid metabolism and inflammation via both the induction and repression of target genes. Given the importance of cholesterol regulation and inflammation in the development of cardiovascular disease, it is not surprising that activation of the LXR pathway attenuates various mechanisms underlying atherosclerotic plaque development.2 In this minireview we will discuss the impact of the LXR pathway on both cholesterol metabolism and atherosclerosis. PMID:20631351

Calkin, Anna; Tontonoz, Peter

2010-01-01

82

Immune Activation, Immunosenescence, and Osteoprotegerin as Markers of Endothelial Dysfunction in Subclinical HIV-Associated Atherosclerosis  

PubMed Central

HIV-infected patients have a significantly greater risk of cardiovascular disease. Several markers including osteoprotegerin have been shown to be involved in the development and progression of atherosclerosis. We investigated the relationship between T-cell phenotype, osteoprotegerin, and atherosclerosis evaluated by carotid intima-media thickness (c-IMT) in 94 HIV+ patients on suppressive antiretroviral therapy with Framingham score <10%. As for the control group, 24 HIV-negative subjects were enrolled. c-IMT was assessed by ultrasound. CD4+/CD8+ T-cell activation (CD38+ HLADR+) and senescence (CD57+ CD28?) were measured by flow cytometry. IL-6 and OPG levels were measured by ELISA kit. c-IMT was higher in HIV+ than in controls. Among HIV+ patients, 44.7% had pathological c-IMT (?0.9?mm). CD8+ T-cell activation and senescence and OPG plasma levels were higher in HIV+ patients than in controls. Subjects with pathological c-IMT exhibited higher CD8+ immune activation and immunosenescence and OPG levels than subjects with normal c-IMT. Multivariate analysis showed that age, CD8+ CD38+ HLADR+, and CD8+ CD28? CD57+ were independently associated with pathological c-IMT. Several factors have been implicated in the pathogenesis of atherosclerosis in HIV patients. Immune activation and immunosenescence of CD8+ T cell together with OPG plasma levels might be associated with the development and progression of early atherosclerosis, even in the case of viral suppression. PMID:25374442

D'Abramo, Alessandra; Zingaropoli, Maria Antonella; Oliva, Alessandra; D'Agostino, Claudia; Al Moghazi, Samir; De Luca, Giulia; Iannetta, Marco; Mastroianni, Claudio Maria; Vullo, Vincenzo

2014-01-01

83

Atherosclerosis in native Greenlanders. An ultrasonographic investigation.  

PubMed

A low frequency of ischemic heart disease in Eskimos (Inuit) has been regarded as an expression of absent or low atherosclerosis. The true extent of atherosclerosis in the Eskimo populations of the World is not known due to low autopsy activity. In order to register atherosclerotic changes in the carotid and femoral arteries 61 Native Greenlanders from two settlements with a traditional Eskimo life style in the Uummannaq district of Northwestern Greenland were examined ultrasonographically with a portable scanner (Aloka) using a 7.5 MHz 4 cm linear array transducer. The results obtained were compared to an age and sex matched urban control group of 122 Danes from Copenhagen. The investigation showed that the Native Greenlanders had almost the same degree and extent of atherosclerosis in the carotid and femoral arteries as the Danes. Thus, the low incidence of ischemic heart disease in Native Greenlanders may not be attributed to lesser atherosclerosis. Further studies, particularly autopsy studies are needed. PMID:2206175

Hansen, J P; Hancke, S; Møller-Petersen, J

1990-07-01

84

Atherosclerosis and the internal mammary arteries  

SciTech Connect

One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

Singh, R.N.

1983-06-01

85

Lipid transfer proteins (LTP) and atherosclerosis  

Microsoft Academic Search

This review deals with four lipid transfer proteins (LTP): three are involved in cholesteryl ester (CE) synthesis or transport, the fourth deals with plasma phospholipid (PL) transfer. Experimental models of atherosclerosis, clinical and epidemiological studies provided information as to the relationship of these LTP(s) to atherosclerosis, which is the main focus of this review. Thus, inhibition of acyl-CoA:cholesterol acyltransferase (ACAT)

O. Stein; Y. Stein

2005-01-01

86

Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice  

PubMed Central

Abstract Aim: A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear. Results: To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4+/+/apoE?/?). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE?/? mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4+/+/apoE?/? mice than in apoE?/? mice. Bone marrow transplantation from hPRDX4+/+ donors to apoE?/? mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression. Innovation: In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE?/? mice fed a high-cholesterol diet. Conclusion: These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques. Antioxid. Redox Signal. 17, 1362–1375. PMID:22548251

Guo, Xin; Tanimoto, Akihide; Ding, Yan; Wang, Ke-Yong; Shimajiri, Shohei; Murata, Yoshitaka; Kimura, Satoshi; Tasaki, Takashi; Nabeshima, Atsunori; Watanabe, Teruo; Kohno, Kimitoshi; Sasaguri, Yasuyuki

2012-01-01

87

Positron Emission Tomography Imaging of Atherosclerosis  

PubMed Central

Atherosclerosis-related cardiovascular events are the leading causes of death in the industrialized world. Atherosclerosis develops insidiously and the initial manifestation is usually sudden cardiac death, stroke, or myocardial infarction. Molecular imaging is a valuable tool to identify the disease at an early stage before fatal manifestations occur. Among the various molecular imaging techniques, this review mainly focuses on positron emission tomography (PET) imaging of atherosclerosis. The targets and pathways that have been investigated to date for PET imaging of atherosclerosis include: glycolysis, cell membrane metabolism (phosphatidylcholine synthesis), integrin ?v?3, low density lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1), macrophages, platelets, etc. Many PET tracers have been investigated clinically for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET imaging can help to prevent the premature death caused by atherosclerosis, and smooth translation of promising PET tracers into the clinic is critical to the benefit of patients. PMID:24312158

Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo

2013-01-01

88

Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis  

Microsoft Academic Search

The role of the immune system in modulating atherosclerosis has recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study

Jacob George; Arnon Afek; Boris Gilburd; Hana Levkovitz; Aviv Shaish; Iris Goldberg; Yuri Kopolovic; Georg Wick; Yehuda Shoenfeld; Dror Harats

1998-01-01

89

Osteoprotegerin, vascular calcification and atherosclerosis  

PubMed Central

The association of bone pathologies with atherosclerosis has stimulated the search for common mediators linking the skeletal and the vascular system. Since its initial discovery as a key regulator in bone metabolism, osteoprotegerin (OPG) has become the subject of intense interest for its role in vascular disease and calcification. Studies in vitro and in animal models suggest that OPG inhibits vascular calcification. Paradoxically however, clinical studies suggest that serum OPG levels increase in association with vascular calcification, coronary artery disease, stroke and future cardiovascular events. This has led to extensive debate on the potential of OPG as a biomarker of vascular disease. However the exact significance and mechanisms by which this bone-regulatory protein influences cardiovascular pathophysiology is still unclear. The need for a more complete picture is being addressed in increasing valuable research indicating OPG as not only a marker but also a mediator of vascular pathology modulating osteogenic, inflammatory and apoptotic responses. By integrating the results of recent experimental research, animal models and clinical studies, this review summarises the present understanding of the role of OPG in vascular disease and calcification. PMID:19007931

Van Campenhout, Ann; Golledge, Jonathan

2009-01-01

90

Nitric oxide function in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

Matthys, K. E.

1997-01-01

91

Optimal therapeutic strategy for treating patients with hypertension and atherosclerosis: focus on olmesartan medoxomil  

PubMed Central

Cardiovascular (CV) disease is a major factor in mortality rates around the world and contributes to more than one-third of deaths in the US. The underlying cause of CV disease is atherosclerosis, a chronic inflammatory process that is clinically manifested as coronary artery disease, carotid artery disease, or peripheral artery disease. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Consequently, developing a treatment regimen that can slow or even reverse the atherosclerotic process is imperative. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with CV risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. Since the renin–angiotensin–aldosterone system (RAAS) plays a key role in vascular inflammatory responses, hypertension treatment with RAAS-blocking agents (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]) may slow inflammatory processes and disease progression. Reduced nitric oxide (NO) bioavailability has an important role in the process of endothelial dysfunction and hypertension. Therefore, agents that increase NO and decrease oxidative stress, such as ARBs and ACEIs, may interfere with atherosclerosis. Studies show that angiotensin II type 1 receptor antagonism with an ARB improves endothelial function and reduces atherogenesis. In patients with hypertension, the ARB olmesartan medoxomil provides effective blood pressure lowering, with inflammatory marker studies demonstrating significant RAAS suppression. Several prospective, randomized studies show vascular benefits with olmesartan medoxomil: reduced progression of coronary atherosclerosis in patients with stable angina pectoris (OLIVUS); decreased vascular inflammatory markers in patients with hypertension and micro- (pre-clinical) inflammation (EUTOPIA); improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis (MORE); and resistance vessel remodeling in patients with stage 1 hypertension (VIOS). Although CV outcomes were not assessed in these studies, the observed benefits in surrogate endpoints of disease suggest that RAAS suppression with olmesartan medoxomil may potentially have beneficial effects on CV outcomes in these patient populations. PMID:21796255

Mason, R Preston

2011-01-01

92

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension 1 1 This study was sponsored by Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey  

Microsoft Academic Search

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations

M. Kochar; R. Guthrie; J. Triscari; K. Kassler-Taub; R. A. Reeves

1999-01-01

93

Effects of rosuvastatin combined with olmesartan, irbesartan, or telmisartan on indices of glucose metabolism in greek adults with impaired fasting glucose, hypertension, and mixed hyperlipidemia: A 24-week, randomized, open-label, prospective study  

Microsoft Academic Search

Background: Statin therapy has been reported to be associated with new-onset diabetes. Angiotensin II-receptor blockers (ARBs) are effective antihypertensive drugs that have been reported to activate peroxisome proliferator-activated receptor ? (PPAR?) to differing extents, with favorable effects on glucose metabolism and the incidence of new-onset diabetes. Among the ARBs, telmisartan is a partial activator of PPAR?, irbesartan is a weak

Christos V. Rizos; Haralampos J. Milionis; Michael S. Kostapanos; Matilda Florentin; Christina E. Kostara; Moses S. Elisaf; Evangelos N. Liberopoulos

2010-01-01

94

Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis  

PubMed Central

The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL's inductive effects and avoiding the ox-LDL's inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future. PMID:24222847

Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

2013-01-01

95

Metabonomics-based omics study and atherosclerosis  

PubMed Central

Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination with proteomics and transcriptomics as the part of a systems biology description to understand the genome interaction with the development of atherosclerosis. The present review describes the application of metabonomics to explore the potential role of metabolic disturbances and inflammation in the initiation and development of atherosclerosis. Metabonomics-based omics study offers a new potential for biomarker discovery by disentangling the impacts of diet, environment and lifestyle. PMID:22040517

2011-01-01

96

Infectious burden and atherosclerosis: A clinical issue  

PubMed Central

Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

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

2014-01-01

97

The biological role of inflammation in atherosclerosis.  

PubMed

The concept of the involvement of inflammation in the pathogenesis of atherosclerosis has existed since the 1800s, stemming from sentinel pathologic observations made by Rudolf Virchow, Karl Rokitansky, and others. Our understanding of the complex role played by immune and inflammatory mediators in the initiation and progression of atherosclerosis has evolved considerably in the intervening years, and today, a dramatically evolved understanding of these processes has led to advances in both diagnostic and prognostic approaches, as well as novel treatment modalities targeting inflammatory and immune mediators. Therapeutic interventions working through multiple mechanisms involved in atheroma pathogenesis, such as statins, which both lower lipids and alter the inflammatory milieu in the vessel wall, hold promise for the future. In this brief review, we explore the biological role of inflammation in atherosclerosis, with a focus on cellular involvement in both acute and chronic inflammation, and outline novel biomarkers of inflammation and atherosclerosis with a particular focus on the potential application of these novel approaches in improving strategies for disease diagnosis and management. PMID:22985787

Wong, Brian W; Meredith, Anna; Lin, David; McManus, Bruce M

2012-01-01

98

Metabolomic analyses for atherosclerosis, diabetes, and obesity  

PubMed Central

Insulin resistance associated with type 2 diabetes mellitus (T2DM), obesity, and atherosclerosis is a global health problem. A portfolio of abnormalities of metabolic and vascular homeostasis accompanies T2DM and obesity, which are believed to conspire to lead to accelerated atherosclerosis and premature death. The complexity of metabolic changes in the diseases presents challenges for a full understanding of the molecular pathways contributing to the development of these diseases. The recent advent of new technologies in this area termed “Metabolomics” may aid in comprehensive metabolic analysis of these diseases. Therefore, metabolomics has been extensively applied to the metabolites of T2DM, obesity, and atherosclerosis not only for the assessment of disease development and prognosis, but also for the biomarker discovery of disease diagnosis. Herein, we summarize the recent applications of metabolomics technology and the generated datasets in the metabolic profiling of these diseases, in particular, the applications of these technologies to these diseases at the cellular, animal models, and human disease levels. In addition, we also extensively discuss the mechanisms linking the metabolic profiling in insulin resistance, T2DM, obesity, and atherosclerosis, with a particular emphasis on potential roles of increased production of reactive oxygen species (ROS) and mitochondria dysfunctions. PMID:24252331

2013-01-01

99

Cannabinoids for therapeutic use in atherosclerosis 1  

Microsoft Academic Search

Summary Atherosclerosis remains the primary cause of heart disease and stroke that causes about 50% of all deaths in Western countries. The identification of promising novel anti-athero- sclerotic therapeutics is therefore of great interest and represents a continued challenge to the medical community. Cannabinoids, such as D9-tetrahydro- cannabinol (THC), the major psychoactive compound of marijuana, their synthetic ana- logs and

Sabine Steffens

2006-01-01

100

Circulating transcriptome reveals markers of atherosclerosis  

PubMed Central

Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the in vivo transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel–Biskis–Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein. In vitro inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases. PMID:15728378

Patino, Willmar D.; Mian, Omar Y.; Kang, Ju-Gyeong; Matoba, Satoaki; Bartlett, Linda D.; Holbrook, Brenda; Trout, Hugh H.; Kozloff, Louis; Hwang, Paul M.

2005-01-01

101

ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.  

PubMed

Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate-binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin(-)Sca-1(+)Kit+ (LSK) in the bone marrow. Transplantation of Abca1(-/-) Abcg1(-/-) bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis. PMID:20488992

Yvan-Charvet, Laurent; Pagler, Tamara; Gautier, Emmanuel L; Avagyan, Serine; Siry, Read L; Han, Seongah; Welch, Carrie L; Wang, Nan; Randolph, Gwendalyn J; Snoeck, Hans W; Tall, Alan R

2010-06-25

102

ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation  

PubMed Central

Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate–binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin? Sca-1+Kit+ (LSK) in the bone marrow. Transplantation of Abca1?/? Abcg1?/? bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis. PMID:20488992

Yvan-Charvet, Laurent; Pagler, Tamara; Gautier, Emmanuel L.; Avagyan, Serine; Siry, Read L.; Han, Seongah; Welch, Carrie L.; Wang, Nan; Randolph, Gwendalyn J.; Snoeck, Hans W.; Tall, Alan R.

2011-01-01

103

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by ultra high performance liquid chromatography tandem mass spectrometry and its application to a bioequivalence study.  

PubMed

An ultra high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) method was developed and validated to determine irbesartan (IRB) and hydrochlorothiazide (HCTZ) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on an Acquity U-HPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the negative ion mode. The MRM transitions of m/z 427.2?206.9 and m/z 296.1?204.9 were used to quantify for IRB and HCTZ, respectively. The linearity of this method was found to be within the concentration range of 5-3000ng/mL for IRB, and 0.5-300ng/mL for HCTZ in human plasma, respectively. The lower limit of quantification (LLOQ) was 5ng/mL and 0.5ng/mL for IRB and HCTZ in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 12% for both IRB and HCTZ. The analysis time of per sample was 2.5min. The developed and validated method was successfully applied to a bioequivalence study of IRB (300mg) with HCTZ (12.5mg) tablet in Chinese healthy volunteers (N=20). PMID:24681823

Qiu, Xiangjun; Wang, Zhe; Wang, Bing; Zhan, Hui; Pan, Xiaofeng; Xu, Ren-ai

2014-04-15

104

Atherosclerosis, Dementia, and Alzheimer's Disease in the BLSA Cohort  

PubMed Central

Objective Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts. Methods We examined the relationship between systemic atherosclerosis, Alzheimer type pathology and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging (BLSA), a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies. Results Using a quantitative analysis of atherosclerosis in the aorta, heart and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer’s type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible. Interpretation Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer’s pathology and stroke through which vascular changes may influence dementia risk. PMID:20695015

Dolan, Hillary; Crain, Barbara; Troncoso, Juan; Resnick, Susan M; Zonderman, Alan B; OBrien, Richard J

2011-01-01

105

Connecting the Lines between Hypogonadism and Atherosclerosis  

PubMed Central

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research. PMID:22518131

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

106

Atherosclerosis: current pathogenesis and therapeutic options.  

PubMed

Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their receptors. New pro- and anti-inflammatory pathways linking lipid and inflammation biology have been discovered, and genetic profiling studies have unveiled variations involved in human CAD. The growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms that can be exploited to complement lipid-lowering therapies. Here we aim to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD. PMID:22064431

Weber, Christian; Noels, Heidi

2011-01-01

107

Monocytes in atherosclerosis: subsets and functions  

PubMed Central

Chronic inflammation drives atherosclerosis, the leading cause of cardiovascular disease. Over the past two decades, data have emerged showing that immune cells are involved in the pathogenesis of atherosclerotic plaques. The accumulation and continued recruitment of leukocytes are associated with the development of ‘vulnerable’ plaques. These plaques are prone to rupture, leading to thrombosis, myocardial infarction or stroke, all of which are frequent causes of death. Plaque macrophages account for the majority of leukocytes in plaques, and are believed to differentiate from monocytes recruited from circulating blood. However, monocytes represent a heterogenous circulating population of cells. Experiments are needed to address whether monocyte recruitment to plaques and effector functions, such as the formation of foam cells, the production of nitric oxide and reactive oxygen species, and proteolysis are critical for the development and rupture of plaques, and thus for the pathophysiology of atherosclerosis, as well as elucidate the precise mechanisms involved. PMID:20065951

Woollard, Kevin J.; Geissmann, Frederic

2010-01-01

108

PPARs in atherosclerosis: the clot thickens  

PubMed Central

Cardiovascular disease is the leading cause of morbidity and mortality in Western countries. Previous studies have highlighted the beneficial effects of PPAR? activators on cardiovascular disease; however, the role of other PPAR family members in atherosclerosis is less clear. A report in this issue of the JCI expands our understanding of PPARs in vascular biology and highlights the potential use of multiple PPAR agonists to limit lipid accumulation in macrophages. PMID:15578084

Castrillo, Antonio; Tontonoz, Peter

2004-01-01

109

Organ and Metabolic Complications: Lipids\\/Atherosclerosis  

Microsoft Academic Search

The incidence of and mortality from atherosclerotic complications, particulary coronary atherosclerosis, is strikingly increased\\u000a in dialysed patients. One of the factors involved is dyslipoproteinemia. The main cause of dyslipoproteinemia is reduced activity\\u000a of enzymes catabolising lipoproteins (hepatic triglyceride lipase, lipoprotein lipase), but additional abnormalities clearly\\u000a contribute. Specific patterns of dyslipoproteinemia are present in patients with the nephrotic syndrome, diabetes mellitus

Eberhard Ritz; Michal Nowicki; Andrzej Wiecek

110

Role of macrophage scavenger receptors in atherosclerosis.  

PubMed

Accumulating evidence indicates that atherosclerosis is a chronic inflammatory disease. The key innate immune cells that are involved in the pathogenesis of atherosclerosis are circulating monocytes and plaque macrophages. Complex interplay between immune and metabolic processes results in pathological activity of these cells. The best understood pathological process mediated by macrophages is their inability to process modified lipoproteins properly resulting in the formation of foamy cells, which are a dangerous component of atherosclerotic plaques. Key molecules involved in the recognition and processing of modified lipoproteins are scavenger receptors (SR). This is a large family of surface expressed structurally heterogeneous receptors with a broad spectrum of endogenous and exogenous ligands. The common functional feature of SR is internalisation of extracellular components and targeting them for lysosomal degradation. However, these relatively simple functions can have complex consequences, since they are linked to diverse specific signalling pathways and to other membrane transport pathways. Moreover, scavenger receptors can co-operate with other types of receptors increasing the variability of the macrophage response to multiple extracellular ligands. At least some SRs respond to modified lipoproteins by amplification of inflammation and accumulation of macrophages in the plaque, while some SRs may support tolerogenic reactions. Outcome of different SR activities will be the decision of monocytes and macrophage to guard homeostatic balance, support atherosclerosis progression and plaque instability by inflammatory reactions, or support rapid fibrotic processes in the plaque that stabilise it. Despite the accumulating knowledge about the molecular mechanisms of scavenger receptor action, their role in the progression of atherosclerosis remains controversial. The activities of scavenger receptors that can contribute to each of these processes are a subject of current review. PMID:22437077

Kzhyshkowska, Julia; Neyen, Claudine; Gordon, Siamon

2012-05-01

111

Von Willebrand factor deficiency and atherosclerosis.  

PubMed

Von Willebrand factor (VWF) is a large multimeric glycoprotein that plays a major role in haemostasis, illustrated by the bleeding tendency in von Willebrand disease (VWD), the most common hereditary bleeding disorder caused by VWF deficiency or dysfunction. Elevated VWF levels are strongly associated with an increased risk of ischemic cardiovascular events. Whether this relation is causal, or whether increased VWF levels reflect disturbances of endothelial function remains to be elucidated. One possibility is that VWF participates in the process of atherogenesis. The aim of the current review is to determine whether VWF deficiency provides protection against the development of atherosclerosis in humans and animals. Results from animal studies suggest that, at arterial branch point predilection sites, VWF deficiency or blockage has a protective effect against atherosclerosis. Based on the available evidence, this potential protective effect of VWF deficiency can most likely be tracked to the VWF-platelet interaction. Sites involved in this interaction could prove attractive targets in future treatment and prevention of cardiovascular disease, an option that is already being explored in humans. An unequivocal protective effect of VWD on atherosclerosis has not been demonstrated in humans. However the interpretation of these results is hampered by several methodological weaknesses. In conclusion, VWF is probably a significant player in the multifaceted interaction between the haemostatic system and the atherosclerotic process which deserves further study. PMID:22721874

van Galen, K P M; Tuinenburg, A; Smeets, E M; Schutgens, R E G

2012-09-01

112

Impact of matrix metalloproteinases on atherosclerosis.  

PubMed

Atherosclerosis is now widely recognized as a chronic inflammatory disease that involves innate and adaptive immune responses. Both cellular and humoral components of the immune system have been implicated in atherogenesis. Growing evidence suggests that immune cells play crucial roles in atherogenic plaque formation. Vulnerability of the plaque probably plays an important role in rupture. Most ruptures occur at the periphery of the fibrous cap that covers the lipid-rich core-points where the cap is usually thinnest and most heavily infiltrated by macrophage foam cells. Sudden rupture of a plaque triggers unstable angina, acute myocardial infarction, and sudden cardiac death. Initiation of collagen breakdown in plaques requires matrix metalloproteinase (MMP) family members including MMP-1, MMP-8, and MMP- 13. In addition, other MMPs such as MMP-2, -3, -9, -10 and -12 have also been reported to play roles in atherosclerosis. This review aims to focus on description of general structural features of MMPs and their roles in atherosclerosis. PMID:24517161

Lin, Juntang; Kakkar, Vijay; Lu, Xinjie

2014-04-01

113

Mouse models for atherosclerosis and pharmaceutical modifiers.  

PubMed

Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in humans. The mouse is the most useful, economic, and valid model for studying atherosclerosis and exploring effective therapeutic approaches. Among the most widely used mouse models for atherosclerosis are apolipoprotein E-deficient (ApoE-/-) and LDL receptor-deficient (LDLr-/-) mice. An up-and-coming model is the ApoE*3Leiden (E3L) transgenic mouse. Here, we review studies that have explored how and to what extent these mice respond to compounds directed at treatment of the risk factors hypercholesterolemia, hypertriglyceridemia, hypertension, and inflammation. An important outcome of this survey is that the different models used may differ markedly from one another in their response to a specific experimental manipulation. The choice of a model is therefore of critical importance and should take into account the risk factor to be studied and the working spectrum of the compounds tested. PMID:17541027

Zadelaar, Susanne; Kleemann, Robert; Verschuren, Lars; de Vries-Van der Weij, Jitske; van der Hoorn, José; Princen, Hans M; Kooistra, Teake

2007-08-01

114

Atherosclerosis and Atheroma Plaque Rupture: Normal Anatomy of Vasa Vasorum and Their Role Associated with Atherosclerosis  

PubMed Central

Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage. PMID:24790560

2014-01-01

115

Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis  

PubMed Central

Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Recent advances in the understanding of lipid metabolism have revealed that miR-33, an intronic microRNA located within the SREBF2 gene, suppresses expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be atheroprotective. As the regression of atherosclerosis is clinically desirable, we assessed the impact of miR-33 inhibition in mice deficient for the LDL receptor (Ldlr–/– mice), with established atherosclerotic plaques. Mice treated with anti-miR33 for 4 weeks showed an increase in circulating HDL levels and enhanced reverse cholesterol transport to the plasma, liver, and feces. Consistent with this, anti-miR33–treated mice showed reductions in plaque size and lipid content, increased markers of plaque stability, and decreased inflammatory gene expression. Notably, in addition to raising ABCA1 levels in the liver, anti-miR33 oligonucleotides directly targeted the plaque macrophages, in which they enhanced ABCA1 expression and cholesterol removal. These studies establish that raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression and suggest that it may be a promising strategy to treat atherosclerotic vascular disease. PMID:21646721

Rayner, Katey J.; Sheedy, Frederick J.; Esau, Christine C.; Hussain, Farah N.; Temel, Ryan E.; Parathath, Saj; van Gils, Janine M.; Rayner, Alistair J.; Chang, Aaron N.; Suarez, Yajaira; Fernandez-Hernando, Carlos; Fisher, Edward A.; Moore, Kathryn J.

2011-01-01

116

The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis  

PubMed Central

SUMMARY Chronic inflammation is a hallmark of atherosclerosis, but its transcriptional underpinnings are poorly understood. We show that the transcriptional repressor Bcl6 is an anti-inflammatory regulator whose loss in bone marrow of Ldlr?/? mice results in severe atherosclerosis and xanthomatous tendonitis, a virtually pathognomonic complication in patients with familial hypercholesterolemia. Disruption of the interaction between Bcl6 and SMRT or NCoR with a peptide inhibitor in vitro recapitulated atherogenic gene changes in mice transplanted with Bcl6-deficient bone marrow, pointing to these cofactors as key mediators of Bcl6 inflammatory suppression. Using ChIP-seq, we reveal the SMRT and NCoR co-repressor cistromes, each consisting of over 30,000 binding sites with a nearly 50% overlap. While the complete cistromes identify a diversity of signaling pathways, the Bcl6-bound sub-cistromes for each co-repressor are highly enriched for NF-?B-driven inflammatory and tissue remodeling genes. These results reveal that Bcl6-SMRT/NCoR complexes constrain immune responses and contribute to the prevention of atherosclerosis. PMID:22465074

Barish, Grant D.; Yu, Ruth T.; Karunasiri, Malith S.; Becerra, Diana; Kim, Jason; Tseng, Tiffany W.; Tai, Li-Jung; LeBlanc, Matthias; Diehl, Cody; Cerchietti, Leandro; Miller, Yury I.; Witztum, Joseph L.; Melnick, Ari M.; Dent, Alexander L.; Tangirala, Rajendra K.; Evans, Ronald M.

2012-01-01

117

Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice.  

PubMed

Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr(-/-) mice reconstituted with Akt1(-/-) fetal liver cells (Akt1(-/-)?Ldlr(-/-)) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT?Ldlr(-/-)). In contrast, Akt2(-/-)?Ldlr(-/-) mice had dramatically reduced atherosclerotic lesions compared with WT?Ldlr(-/-) mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2(-/-)?Ldlr(-/-) mice had smaller aortic lesions compared with WT?Ldlr(-/-) and Akt1(-/-)?Ldlr(-/-) mice. Importantly, Akt2(-/-)?Ldlr(-/-) mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6C(hi) and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2(-/-) mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis. PMID:25240046

Babaev, Vladimir R; Hebron, Katie E; Wiese, Carrie B; Toth, Cynthia L; Ding, Lei; Zhang, Youmin; May, James M; Fazio, Sergio; Vickers, Kasey C; Linton, MacRae F

2014-11-01

118

Experimental models investigating the inflammatory basis of atherosclerosis  

Microsoft Academic Search

Inflammation is considered an important aspect in the development of atherosclerosis. Genetic manipulations of animal models\\u000a susceptible to atherosclerosis have unraveled the contribution of various inflammatory pathways implicated in the development\\u000a of atherosclerosis. These inflammatory pathways not only lead to the recruitment and entry of inflammatory cells into the\\u000a arterial wall, they also modify the morphology and composition of atherosclerotic

Ahmed Soliman; Patrick Kee

2008-01-01

119

Macrophage Activation in Atherosclerosis: Pathogenesis and Pharmacology of Plaque Rupture  

Microsoft Academic Search

Atherosclerosis is still an important disease. It accounts for 39% of deaths in the U.K. and 12 million U.S citizens have atherosclerosis-associated disease. Atherosclerosis may exert clinical effects by slow narrowing, producing stable angina or dramatic rupture, producing acute coronary syndromes such as unstable angina or myocardial infarction and death. Macrophages are abundant in ruptured atherosclerotic plaques. Macrophages are innate

J. J. Boyle

2005-01-01

120

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis  

E-print Network

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a ...

Kim, YongTae

121

Follow-up of cardiovascular risk markers in hypertensive patients treated with irbesartan: results of the i-SEARCH Plus Registry.  

PubMed

Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63-203.40) pg/mL. In patients with MAU (ACR ?20mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49-4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39-7.68) and death (OR, 4.63; 95%CI, 1.44-14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP. PMID:21122056

Tebbe, Ulrich; Bramlage, Peter; Lüders, Stephan; Cuneo, Alessandro; Sistig, Peter; de Haan, Fokko; Schmieder, Roland; Böhm, Michael; Paar, W Dieter; Schrader, Jochen

2010-12-01

122

RNA interference therapy: a new solution for intracranial atherosclerosis?  

PubMed Central

Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery, especially middle cerebral artery (MCA), is reported to be one leading cause of ischemic stroke throughout the world. Compared with other stroke subtypes, ICAS is associated with a higher risk of recurrent stroke despite aggressive medical therapy. Increased understanding of the pathophysiology of ICAS has highlighted several possible targets for therapeutic interventions. Both luminal stenosis and plaque components of ICAS have been found to be associated with ischemic stroke based a post-mortem study. Recent application of high-resolution magnetic resonance imaging (HRMRI) in evaluating ICAS provides new insight into the vascular biology of plaque morphology and component. High signal on T1-weighted fat-suppressed images (HST1) within MCA plaque of HRMRI, highly suggested of fresh or recent intraplaque hemorrhage, has been found to be associated with ipsilateral brain infarction. Thus, the higher prevalence of intraplaque hemorrhage and neovasculature in symptomatic patients with MCA stenosis may provide a potential target for plaque stabilization. We hypothesize that RNA interference (RNAi) therapy delivered by modified nanoparticles may achieve in vivo biomedical imaging and targeted therapy. With the rapid developments in studies about therapeutic and diagnostic nanomaterials, future studies further exploring the molecular biology of atherosclerosis may provide more drug targets for plaque stabilization.

Tang, Tao; Wong, Ka-Sing

2014-01-01

123

Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?  

SciTech Connect

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.

Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp; Seko, Ayumi; Sonoda, Akinaga; Ohta, Shinichi; Tanaka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi [Shiga University of Medical Science, Department of Radiology (Japan); Takemura, Shizuki [Shiga University of Medical Science, Department of Pathology (Japan); Sakamoto, Tsutomu [Koka General Hospital, Department of Radiology (Japan); Tabata, Yasuhiko [Kyoto University, Department of Biomaterials, Field of Tissue Engineering (Japan)

2008-03-15

124

Reversibility of atherosclerosis--evolving perspectives from two arterial imaging clinical trials: the cholesterol lowering atherosclerosis regression study and the monitored atherosclerosis regression study.  

PubMed

The Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) are serial arterial imaging clinical trials that have explored the reversibility of atherosclerosis with lipid-lowering therapy in native coronary, carotid, and femoral arterial beds, as well as in coronary artery bypass grafts. Results demonstrate that progression of atherosclerosis can be reduced in all these vascular beds. Evolving data indicate that coronary lesions > or = 50% diameter stenosis (%S) at baseline respond more readily to lipid-lowering therapy than lesions <50%S. In addition, lipoproteins may have a differential effect on coronary lesion progression according to lesion size, with triglyceride-rich lipoproteins playing an important role in the progression of lesions <50%S. Limited data indicate that progression of atherosclerosis in women may be more responsive to lipid-lowering therapy than in men, and that estrogen replacement may enhance the anti-atherosclerosis effects of lipid lowering. Longitudinal measurements of carotid artery far wall intima-media thickness (IMT) with B-mode ultrasonography in CLAS and MARS indicate that carotid atherosclerosis at a stage before lesions intrude into the vessel lumen can be reduced by lipid-lowering therapy. Together, CLAS and MARS data indicate that the spectrum from very early lesions confined to the arterial wall to established lesions late in the atherosclerotic process can be reversed with lipid-lowering therapy. PMID:8907211

Hodis, H N

1995-01-01

125

Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice.  

PubMed

The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. PMID:25261526

Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

2014-12-15

126

Adiponectin Abates Atherosclerosis by Reducing Oxidative Stress  

PubMed Central

Background We investigated whether the anti-atherosclerosis of adiponectin (APN) relates to the reduction of oxidative stress. We observed the overexpression of adiponectin gene with different titers on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE?/?) mice. Material/Methods We divided 48 male ApoE?/? mice into 4 groups: control group, high-fat diet group, low adiponectin group, and high adiponectin group. The low and high adiponectin group mice were treated with recombinant adenovirus expressing mice adiponectin (Ad-APN) with low-dose adiponectin 1.0×108 p.f.u. and high-dose adiponectin 5.0×108 p.f.u. via the tail every 2 weeks and given a high-fat diet for the last 8 weeks. On the 14th day after injection, blood samples were obtained from the vena cava. Results Along with increased serum adiponectin, serum superoxide dismutase (SOD) activity increased (P<0.05) and concentration of malondialdehyde (MDA) was decreased (P<0.05). Levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, especially TC and LDL-C (P<0.05). A real-time fluorescent quantitative polymerase chain reaction test was used to analyze levels of mRNA expression for endothelial nitric oxide synthase (eNOS) and adiponectin in the aorta. Along with increased adiponectin, the mRNA expression of eNOS in the aorta was increased significantly (P<0.05). The lesion formation in the aortic sinus was inhibited by 25% and 31% in the low-APN group and high-APN group, respectively (P<0.05). Along with the increase of adiponectin doses, the damage of atherosclerosis gradually eased. However, the differences between the low-APN group and high-APN group had no statistical significance. Conclusions Adiponectin may protect the aorta from atherosclerosis injury by reducing oxidative stress, reducing lesion formation size in the aortic root and reducing TC, TG, and LDL-C in serum. The molecular mechanism may involve preservation of SOD, reducing MDA in serum, and increasing eNOS and adiponectin mRNA expression in the aorta. PMID:25275545

Wang, Xuemei; Pu, Hongwei; Ma, Chuang; Jiang, Tao; Wei, Qin; Duan, Mingjun; Zhang, Chun; Shou, Xi; Su, Lipin; Zhang, Jianlong; Yang, Yining

2014-01-01

127

Adiponectin abates atherosclerosis by reducing oxidative stress.  

PubMed

Background We investigated whether the anti-atherosclerosis of adiponectin (APN) relates to the reduction of oxidative stress. We observed the overexpression of adiponectin gene with different titers on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE-/-) mice. Material and Methods We divided 48 male ApoE-/- mice into 4 groups: control group, high-fat diet group, low adiponectin group, and high adiponectin group. The low and high adiponectin group mice were treated with recombinant adenovirus expressing mice adiponectin (Ad-APN) with low-dose adiponectin 1.0×108 p.f.u. and high-dose adiponectin 5.0×108 p.f.u. via the tail every 2 weeks and given a high-fat diet for the last 8 weeks. On the 14th day after injection, blood samples were obtained from the vena cava. Results Along with increased serum adiponectin, serum superoxide dismutase (SOD) activity increased (P<0.05) and concentration of malondialdehyde (MDA) was decreased (P<0.05). Levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, especially TC and LDL-C (P<0.05). A real-time fluorescent quantitative polymerase chain reaction test was used to analyze levels of mRNA expression for endothelial nitric oxide synthase (eNOS) and adiponectin in the aorta. Along with increased adiponectin, the mRNA expression of eNOS in the aorta was increased significantly (P<0.05). The lesion formation in the aortic sinus was inhibited by 25% and 31% in the low-APN group and high-APN group, respectively (P<0.05). Along with the increase of adiponectin doses, the damage of atherosclerosis gradually eased. However, the differences between the low-APN group and high-APN group had no statistical significance. Conclusions Adiponectin may protect the aorta from atherosclerosis injury by reducing oxidative stress, reducing lesion formation size in the aortic root and reducing TC, TG, and LDL-C in serum. The molecular mechanism may involve preservation of SOD, reducing MDA in serum, and increasing eNOS and adiponectin mRNA expression in the aorta. PMID:25275545

Wang, Xuemei; Pu, Hongwei; Ma, Chuang; Jiang, Tao; Wei, Qin; Zhang, Chun; Duan, Mingjun; Shou, Xi; Su, Lipin; Zhang, Jianlong; Yang, Yining

2014-01-01

128

MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis  

Microsoft Academic Search

Macrophage migration inhibitory factor (MIF) is well established as a key cytokine in immuno-inflammatory diseases such as rheumatoid arthritis. Inflammation is now also recognized as having a crucial role in atherosclerosis, and recent evidence indicates that MIF could also be important in this disease. Here, we review the role of MIF in rheumatoid arthritis and atherosclerosis, discuss the ways in

Michelle Leech; Jürgen Bernhagen; Eric F. Morand

2006-01-01

129

Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice  

Microsoft Academic Search

Reduced estrogen levels result in loss of protec- tion from coronary heart disease in postmenopausal women. Enhanced and diminished atherosclerosis have been associ- ated with plasma levels of cholesteryl ester transfer protein (CETP); however, little is known about the role of CETP- ovarian hormone interactions in atherogenesis. We assessed the severity of diet-induced atherosclerosis in ovariecto- mized (OV) CETP transgenic

Patrícia M. Cazita; Jairo A. Berti; Carolina Aoki; Magnus Gidlund; Lila M. Harada; Valéria S. Nunes; Eder C. R. Quintão; Helena C. F. Oliveira

2003-01-01

130

Quantum dot mediated imaging of atherosclerosis  

NASA Astrophysics Data System (ADS)

The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE-/- mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

Jayagopal, Ashwath; Su, Yan Ru; Blakemore, John L.; Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

2009-04-01

131

Deficiency of the NR4A orphan nuclear receptor NOR1 in hematopoietic stem cells accelerates atherosclerosis.  

PubMed

The NR4A orphan nuclear receptor NOR1 functions as a constitutively active transcription factor regulating cellular inflammation and proliferation. In this study, we used bone marrow transplantation to determine the selective contribution of NOR1 expression in hematopoietic stem cells to the development of atherosclerosis. Reconstitution of lethally irradiated apoE(-/-) mice with NOR1-deficient hematopoietic stem cells accelerated atherosclerosis formation and macrophage recruitment following feeding a diet enriched in saturated fat. NOR1 deficiency in hematopoietic stem cells induced splenomegaly and monocytosis, specifically the abundance of inflammatory Ly6C(+) monocytes. Bone marrow transplantation studies further confirmed that NOR1 suppresses the proliferation of macrophage and dendritic progenitor (MDP) cells. Expression analysis identified RUNX1, a critical regulator of hematopoietic stem cell expansion, as a target gene suppressed by NOR1 in MDP cells. Finally, in addition to inducing Ly6C(+) monocytosis, NOR1 deletion increased the replicative rate of lesional macrophages and induced local foam cell formation within the atherosclerotic plaque. Collectively, our studies demonstrate that NOR1 deletion in hematopoietic stem cells accelerates atherosclerosis formation by promoting myelopoiesis in the stem cell compartment and by inducing local proatherogenic activities in the macrophage, including lesional macrophage proliferation and foam cell formation. PMID:24806827

Qing, Hua; Liu, Yi; Zhao, Yue; Aono, Jun; Jones, Karrie L; Heywood, Elizabeth B; Howatt, Deborah; Binkley, Cassi M; Daugherty, Alan; Liang, Ying; Bruemmer, Dennis

2014-09-01

132

Activated TLR Signaling in Atherosclerosis among Women with Lower Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis  

PubMed Central

Background Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis. Results A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N?=?48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N?=?71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis. Conclusion Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals. PMID:21698167

Huang, Chiang-Ching; Liu, Kiang; Pope, Richard M.; Du, Pan; Lin, Simon; Rajamannan, Nalini M.; Huang, Qi-Quan; Jafari, Nadereh; Burke, Gregory L.; Post, Wendy; E.Watson, Karol; Johnson, Craig; Daviglus, Martha L.; Lloyd-Jones, Donald M.

2011-01-01

133

Laboratory medicine for molecular imaging of atherosclerosis.  

PubMed

Atherosclerotic plaques are the main cause of life threatening clinical endpoints like myocardial infarction and stroke. To prevent these endpoints, the improved early diagnosis and treatment of vulnerable atherosclerotic vascular lesions are essential. Although originally applied for anticancer treatment, recent advances have also showed the considerable potential of nanotechnology for atherosclerosis. Otherwise, one domain of laboratory medicine is the investigation of new biomarkers. Recent research activities have identified the usability of biomarker-targeted nanoparticles for molecular imaging and pharmacologic modification of vulnerable atherosclerotic lesions leading to myocardial infarction or stroke. These investigations have established a new research interface between laboratory medicine, nanotechnology, cardiology/neurology, and radiology. In this review, we discuss inflammatory pathophysiologic mechanisms and biomarkers associated with a vulnerable atherosclerotic plaque phenotype. Further, we will emphasize cardiovascular relevant functionalized nanoparticle biomarker constructs which were developed within the cooperation interface between Laboratory Medicine (anti-inflammatory biomarkers), Nano-Medicine (nanoparticle development), and Radiology (molecular imaging). PMID:25003647

Mangge, Harald; Almer, Gunter; Stelzer, Ingeborg; Reininghaus, Eva; Prassl, Ruth

2014-11-01

134

Chemokines: established and novel targets in atherosclerosis  

PubMed Central

In their role as small chemotactic cytokines, chemokines are crucial mediators and regulators of leukocyte trafficking during immune surveillance and inflammation. Their involvement in the development and progression of inflammatory diseases has been subject of intense investigation. Concordantly, the chemokine system has been explored in search for therapeutic targets to prevent or treat inflammatory disorders, such as atherosclerosis. Targeting the chemokine system offers various entry points for a causative treatment of this widespread and chronic illness. Although this approach has encountered some setbacks, several innovative compounds are currently in an advanced stage of development. In this review, the current standing of this dynamic field is highlighted and the potential advantages and drawbacks of particular strategies are discussed. PMID:22038924

Koenen, Rory R; Weber, Christian

2011-01-01

135

Atherosclerosis staging: imaging using FLIM technique  

NASA Astrophysics Data System (ADS)

In this work it was used fluorescence lifetime imaging (FLIM) to analyze biochemical composition of atherosclerotic plaque. For this purpose an animal experimentation was done with New Zealand rabbits divided into two groups: a control group of 4 rabbits that received a regular diet for 0, 20, 40 and 60 days; and an experimental group of 9 rabbits, divided in 3 subgroups, that were fed with 1% cholesterol diet for 20, 40 and 60 days respectively. The aortas slices stained with europium chlortetracycline were analyzed by FLIM exciting samples at 440 nm. The results shown an increase in the lifetime imaging of rabbits fed with cholesterol. It was observed that is possible to detect the metabolic changes associated with atherosclerosis at an early stage using FLIM technique exciting the tissue around 440 nm and observing autofluorescence lifetime. Lifetimes longer than 1.75 ns suggest the presence of porphyrins in the tissue and consequently, inflammation and the presence of macrophages.

Sicchieri, Leticia B.; Barioni, Marina Berardi; Silva, Mônica Nascimento; Monteiro, Andrea Moreira; Figueiredo Neto, Antonio Martins; Ito, Amando S.; Courrol, Lilia C.

2014-03-01

136

Inflammatory signaling through leukotriene receptors in atherosclerosis.  

PubMed

The atherosclerotic lesion is a site of local production of the lipid-derived inflammatory mediators known as leukotrienes. This production leads to autocrine and paracrine activation of leukotriene receptors of the BLT and CysLT receptor subtypes expressed on leukocytes and structural cells within the vascular wall. Studies in mice, rats, and rabbits have revealed a key role for leukotriene signaling in atherosclerosis, abdominal aneurysms, and intimal hyperplasia. In addition, a major atherosclerotic immune activation may be leukotriene-dependent through mediation of leukocyte cross-talk within the atherosclerotic lesion. Furthermore, leukotrienes induce endothelium-dependent and independent vascular responses. Finally, recent findings indicate that leukotriene-dependent degradation of the extracellular matrix may link this pathway to atherosclerotic plaque instability. Taken together, the leukotriene pathway may represent a putative therapeutic target in the treatment of atherosclerotic vessel disease. PMID:18489853

Bäck, Magnus

2008-06-01

137

Imaging Atherosclerosis and Risk of Plaque Rupture  

PubMed Central

Atherosclerosis imaging strategies can delineate characteristics of plaques at risk of rupture and thrombosis. Structural plaque imaging identifies high-risk plaque features including lipid pools, thin fibrous caps, and intraplaque hemorrhage, among others. New molecular imaging techniques complement structural imaging approaches by illuminating important features of plaque biology, with a prominent focus on detecting inflammation as a high-risk phenotype. As we unravel the molecular and structural characteristics underlying thrombosis-prone plaques, there is significant promise for eventual early identification and prediction of atherosclerotic plaque complications before they occur. Here we focus on recent imaging insights into high-risk arterial plaques, the etiologic agent of acute myocardial infarction (MI), stroke, and sudden cardiac death. PMID:23982263

Osborn, Eric A; Jaffer, Farouc A

2013-01-01

138

Adiponectin and Atherosclerosis in Rheumatoid Arthritis  

PubMed Central

In the present study, we examined the potential impact of adiponectin on carotid ultrasound determined atherosclerosis in 210 (119 black and 91 white) RA patients in mixed regression models. Total adiponectin concentrations were smaller in patients with compared to those without the metabolic syndrome (MetS) defined waist criterion (median (range) = 6.47 (1.23–34.54) versus 8.38 (0.82–85.30)?ng/mL, P = 0.02, resp.); both total and high molecular weight (HMW) adiponectin concentrations were larger in patients with compared to those without joint deformities (7.97 (0.82–85.30) and 3.51 (0.01–35.40) versus 5.36 (1.29–19.49) and 2.34 (0.01–19.49)?ng/mL, P = 0.003 and 0.02, resp.). Total and HMW adiponectin concentrations were associated with carotid artery plaque in patients with MetS waist (odds ratio (95% CI) = 0.87 (0.76–0.99) and 0.92 (0.85–0.99) per 1-standard deviation increment, P = 0.02 for both) and those without joint deformities (odds ratio (95% CI) = 0.94 (0.88–0.99) and 0.94 (0.89–0.99), P = 0.03 for both). Plaque prevalence was lower in patients without compared to those with joint deformities (23.4% versus 42.6, P = 0.004 in multivariable analysis). In RA patients with abdominal obesity or no clinically evident joint damage, adiponectin concentrations are reduced but nevertheless associated with decreased carotid atherosclerosis. PMID:24994945

Dessein, Patrick H.; Tsang, Linda; Solomon, Ahmed; Woodiwiss, Angela J.; Millen, Aletta M. E.; Norton, Gavin R.

2014-01-01

139

Atherosclerosis risk factors in pigeon squabs  

SciTech Connect

The basis for atherosclerosis susceptibility of White Carneau (WC) and resistance of Show Racer (SR) pigeons is not known. Body weight (BW), total serum cholesterol (TSC), growth of the aorta and replication of endothelial cells of the distal thoracic aorta (lesion prone site) of 1, 2 and 4 week old squabs were studied. Aortic measurements were determined morphometrically, and endothelial cell replication was quantitated by 24-hour /sup 3/H-thymidine labeling and whole-mount SEM autoradiography. From hatching to 4 weeks, BW increased more in WC than SR (22 to 473 gm in WC vs 19 to 416 gm in SR, p < 0.05) in WC than SR (197, 243 and 338 mg/dl in WC and 125, 194 and 282 mg/dl in SR). Surface area of the aorta between 1 and 4 weeks increased by 63% (109, 154 and 178 mm/sup 2/) in WC and 44% (101, 140 and 146 mm/sup 2/) in SR. Aortic surface area was significantly larger (0 = 0.002) in the 4 week WC than 4 week SR. /sup 3/H-thymidine labeled endothelial cells at 1, 2 and 4 weeks were 783, 387 and 53 in WC and 674, 283 and 27 cells/mm/sup 2/ in SR. Endothelial replication in the 4 week WC was twice that of the SR and significantly different between breeds at 2 and 4 weeks (p = 0.04; p = 0.02, respectively). Higher TSC, endothelial cell replication and larger aortic surface area in the WC may be contributing factors to increased atherosclerosis susceptibility.

Klumpp, S.A.; Clarkson, T.B.

1986-03-01

140

Maternal undernutrition programmes atherosclerosis in the ApoE*3-Leiden mouse.  

PubMed

Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher; P < 0.001) and TAG (39 % higher; P < 0.001) relative to offspring exposed to a control diet in utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2.61-fold greater lesion area; P < 0.001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease. PMID:18782462

Yates, Zoe; Tarling, Elizabeth J; Langley-Evans, Simon C; Salter, Andrew M

2009-04-01

141

Gene Deficiency in Activating Fc? Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice  

PubMed Central

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fc? receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fc? receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in ?-chain (the common signaling subunit of activating Fc? receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fc? receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fc? receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fc? receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-?B activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fc? receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fc? receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fc? receptor-mediated inflammatory responses could effectively suppress atherosclerosis. PMID:23805273

Mallavia, Benat; Oguiza, Ainhoa; Lopez-Franco, Oscar; Recio, Carlota; Ortiz-Munoz, Guadalupe; Lazaro, Iolanda; Lopez-Parra, Virginia; Egido, Jesus; Gomez-Guerrero, Carmen

2013-01-01

142

Design of a bead holder for thermal atherosclerosis sensor  

E-print Network

Atherosclerosis is a systemic disease that causes plaque accumulation in arteries and diminished endothelial function. Because it is rarely identified until serious symptoms appear, there is value in a noninvasive technique ...

Savage, Christopher (Christopher R.)

2007-01-01

143

[Advance on study in anti-atherosclerosis mechanism of berberine].  

PubMed

Coptis chinensis is a traditional Chinese herb that has the effect of clearing heat and drying dampness, purging fire to eliminate toxin. Berberine is the main alkaloid of C. chinensis, and researches showed recently, berberine had the effect of anti-atherosclerosis. This paper has reviewed the mechanism of berberine in anti-atherosclerosis from anti-inflammation, regulating lipid, decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell proliferation. PMID:19160773

Wu, Min; Wang, Jie

2008-09-01

144

Advance of studies on anti-atherosclerosis mechanism of berberine.  

PubMed

Coptis Chinensis is a traditional Chinese medicine herb that has the effect of clearing heat and drying dampness, purging fire to eliminate toxin. Berberine is the main alkaloid of Coptis Chinensis, and, recent researches showed that berberine had the effect of anti-atherosclerosis. This paper reviewed the anti-atherosclerosis mechanism of berberine, which may be related to regulating lipids, anti-inflammation, decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell proliferation. PMID:20473748

Wu, Min; Wang, Jie; Liu, Long-tao

2010-04-01

145

Advance of studies on anti-atherosclerosis mechanism of berberine  

Microsoft Academic Search

Coptis Chinensis is a traditional Chinese medicine herb that has the effect of clearing heat and drying dampness, purging fire to eliminate\\u000a toxin. Berberine is the main alkaloid of Coptis Chinensis, and, recent researches showed that berberine had the effect of anti-atherosclerosis. This paper reviewed the anti-atherosclerosis\\u000a mechanism of berberine, which may be related to regulating lipids, anti-inflammation, decompression, reducing

Min Wu; Jie Wang; Long-tao Liu

2010-01-01

146

Regression of Atherosclerosis in Monkeys Reduces Vascular Superoxide Levels  

Microsoft Academic Search

Abstract—Superoxide (O2·) in arteries may,contribute to atherosclerosis in part by inactivation of nitric oxide. We hypothesized,that regression of atherosclerosis in nonhuman,primates is associated with a decrease in vascular NAD(P)H oxidase, decreased O2· levels, and improved endothelium-dependent relaxation. Cynomolgus monkeys (n28) were fed an atherogenic diet for 4710 (meanSE) months. In carotid arteries (containing advanced lesions), femoral arteries (moderate lesions), and

Christopher A. Hathaway; Donald D. Heistad; Donald J. Piegors; Francis J. Miller Jr

147

Atherosclerosis Susceptibility Loci Identified in an Extremely Atherosclerosis-Resistant Mouse Strain  

PubMed Central

Background C3H/HeJ (C3H) mice are extremely resistant to atherosclerosis, especially males. To understand the underlying genetic basis, we performed quantitative trait locus (QTL) analysis on a male F2 (the second generation from an intercross between 2 inbred strains) cohort derived from an intercross between C3H and C57BL/6 (B6) apolipoprotein E–deficient (Apoe?/?) mice. Methods and Results Two hundred forty?six male F2 mice were started on a Western diet at 8 weeks of age and kept on the diet for 5 weeks. Atherosclerotic lesions in the aortic root and fasting plasma lipid levels were measured. One hundred thirty?four microsatellite markers across the entire genome were genotyped. Four significant QTLs on chromosomes (Chr) 2, 4, 9, and 15 and 4 suggestive loci on Chr1, Chr4, and Chr7 were identified for atherosclerotic lesions. Unexpectedly, the C3H allele was associated with increased lesion formation for 2 of the 4 significant QTLs. Six loci for high?density lipoprotein (HDL), 6 for non?HDL cholesterol, and 3 for triglycerides were also identified. The QTL for atherosclerosis on Chr9 replicated Ath29, originally mapped in a female F2 cohort derived from B6 and C3H Apoe?/? mice. This locus coincided with a QTL for HDL, and there was a moderate, but statistically significant, correlation between atherosclerotic lesion sizes and plasma HDL cholesterol levels in F2 mice. Conclusions These data indicate that most atherosclerosis susceptibility loci are distinct from those for plasma lipids except for the Chr9 locus, which exerts effect through interactions with HDL. PMID:23938286

Rowlan, Jessica S.; Li, Qiongzhen; Manichaikul, Ani; Wang, Qian; Matsumoto, Alan H.; Shi, Weibin

2013-01-01

148

Study of Coronary Atherosclerosis by Modified American Heart Association Classification of Atherosclerosis-An Autopsy Study  

PubMed Central

Background: The study was designed to assess the atherosclerotic lesions in coronary arteries in cases subjected to autopsy to grade by applying Modified American Heart Association (AHA) classification, evaluate the atheromatous & vulnerable plaques to find out the to age and sex related prevalence of atherosclerosis in the semi-urban & urban population of Jamnagar, a district in Western India. Material & Methods: Autopsy was conducted on 264 cases whose age ranged from 8-79 years, by the conventional technique; heart was removed & dissected along the direction of blood flow. Microscopic assessment of the three main coronary arteries was done. Result: According to Modified AHA classification of atherosclerosis, maximum number of cases were in the 40-49 years age group. Intimal xanthoma was the most common type in all three coronary arteries. The number of males was 168(64%) and females was 96(36%). 59% males & 52% female were affected from atherosclerosis. An intermediate lesion was noted commonly in young individuals (10-39 years) and older individuals (40-79 years) were 46% & 41% respectively. Pathological Intimal thickening was more common in left anterior descending coronary artery compared to others. Thin fibrous cap atheroma was more common in Left circumflex artery than compared to Left anterior descending artery & Right coronary artery. Conclusion: The study highlights the impact of atherosclerotic lesions in the population of Jamnagar, a district in Gujarat state of Western India. The increased amount of intermediate atherosclerotic lesions found in the young population gives an indication that anti-atherogenic preventive measures and drastic dietary & life style modification need to be implemented in young individuals, this will help to prevent coronary artery disease from causing premature death that lead to huge financial burden on the economy and health sector of India. PMID:24392381

Bhanvadia, Viral M.; Desai, Nandini J.; Agarwal, Neeru M.

2013-01-01

149

PPAR?-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis  

PubMed Central

Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor ? (PPAR?) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPAR? activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPAR? agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RGS4, and RGS5, which was associated with suppression of inflammatory and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated macrophages: PPAR? activation increased both total and free Bcl-6 levels and inhibited AngII activation of MAP kinases, p38, and ERK1/2. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of PPAR? activation to inhibit AngII signaling, which is atheroprotective. PMID:18337495

Takata, Yasunori; Liu, Joey; Yin, Fen; Collins, Alan R.; Lyon, Christopher J.; Lee, Chih-Hao; Atkins, Annette R.; Downes, Michael; Barish, Grant D.; Evans, Ronald M.; Hsueh, Willa A.; Tangirala, Rajendra K.

2008-01-01

150

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis  

PubMed Central

Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk. PMID:23563705

Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.; Lewis, James D.; Warrier, Manya; Brown, J. Mark; Krauss, Ronald M.; Tang, W. H. Wilson; Bushman, Frederic D.; Lusis, Aldons J.; Hazen, Stanley L.

2013-01-01

151

Stat3? mitigates development of atherosclerosis in apolipoprotein E-deficient mice  

PubMed Central

The transcription factor Stat3 is an activator of systemic inflammatory genes. Two isoforms of Stat3 are generated by alternative splicing, Stat3? and Stat3?. The ? isoform lacks the transactivation domain but retains other functions, including dimerization and DNA binding. Stat3?-deficient mice exhibit elevated expression of systemic inflammatory genes and are hyperresponsive to lipopolysaccharide, suggesting that Stat3? functions predominantly as a suppressor of systemic inflammation. To test whether Stat3? deficiency would provoke pathologic effects associated with chronic inflammation, we asked whether selective removal of Stat3? would exacerbate the development of atherosclerosis in apolipoprotein E-deficient mice. In apoE?/?Stat3??/? mice atherosclerotic plaque formation was significantly enhanced relative to apoE?/?Stat3?+/+ controls. The ability of Stat3? deficiency to promote atherosclerosis was more pronounced in female mice, but could be unmasked in males by feeding a high fat diet. Infiltrating macrophages were not increased in aortas of apoE?/?Stat3??/? mice. In contrast, the proportion of pro-inflammatory TH17 cells was significantly elevated in aortic infiltrates from apoE?/?Stat3??/? mice, relative to paired apoE?/?Stat3?+/+ littermates. These observations indicate that Stat3? can suppress pathologic sequelae associated with chronic inflammation. Our findings further suggest that in Stat3?-deficient mice the unopposed action of Stat3? may enhance atherogenesis in part by promoting differentiation of TH17 cells. PMID:23619910

Lee, Jihyun; Baldwin, William M.; Lee, Chih-Yuan

2013-01-01

152

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed directable or focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

Carl, James R. (Inventor); Arndt, G. Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, N. Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

2001-01-01

153

Atherosclerosis: from biology to pharmacological treatment  

PubMed Central

A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment. PMID:23097661

Riccioni, Graziano; Sblendorio, Valeriana

2012-01-01

154

Particulate matter air pollution and atherosclerosis.  

PubMed

Particulate matter (PM) air pollution less than 2.5 microm in diameter (PM(2.5)), which is now an all-pervading element of modern-day society, is associated with heightened cardiovascular morbidity and mortality. Not only can short-term PM(2.5) exposure trigger acute cardiovascular events, but longer-term exposure over years augments cardiovascular risk to an even greater extent. One biological mechanism capable of explaining this observation is that chronic exposure may promote the progression and vulnerability of atherosclerotic plaques. Indeed, recent epidemiologic studies have demonstrated an association between ambient PM(2.5) exposure and the presence or extent of atherosclerosis in humans. Several animal experiments have provided corroborating evidence that chronic exposures in fact do enhance the progression and perhaps vulnerability of atherosclerotic lesions. Due to the billions of people continually exposed to PM(2.5), the long-term pro-atherosclerotic effects of this ubiquitous air pollutant are likely to be of enormous and growing global public health importance. PMID:20617466

Brook, Robert D; Rajagopalan, Sanjay

2010-09-01

155

Molecular Imaging of Inflammation in Atherosclerosis  

PubMed Central

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

156

CD3 Antibody and IL-2 Complex Combination Therapy Inhibits Atherosclerosis by Augmenting a Regulatory Immune Response  

PubMed Central

Background Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti?CD3 antibody (CD3?Ab) and IL?2/anti?IL?2 monoclonal antibody complex (IL?2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. Methods and Results We treated apolipoprotein E?deficient mice fed a high?cholesterol diet with vehicle, CD3?Ab, IL?2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD3?Ab or IL?2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6Chigh inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions. Conclusions Our results indicate that in addition to suppressing Teff responses, enhancing Treg?mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis. PMID:24755152

Kasahara, Kazuyuki; Sasaki, Naoto; Yamashita, Tomoya; Kita, Tomoyuki; Yodoi, Keiko; Sasaki, Yoshihiro; Takeda, Masafumi; Hirata, Ken-ichi

2014-01-01

157

Immune mechanisms in atherosclerosis, especially in diabetes type 2.  

PubMed

Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1? (IL-1?), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed. PMID:24194733

Frostegård, Johan

2013-01-01

158

Coronary and carotid atherosclerosis: similarities and differences.  

PubMed

Although a relationship is commonly accepted between coronary and carotid arterial disease, suggesting that atherosclerosis is a systemic condition, the extent of this association and correspondence has not been fully elucidated. This review discusses recent research in this field and highlights areas for future study. The prevalence of severe carotid stenosis increases with prevalence of coronary stenosis, with the latter being found in a significant number of stroke patients, while those with carotid stenosis may be at higher risk of myocardial infarction than stroke. There also appear to be common risk factors (age, diabetes, hypertension, smoking and dyslipidemia), although the effects in both vascular systems may not be identical. Furthermore, while the degree of stenosis in the coronary artery has little ability to predict acute coronary syndrome, which is caused by local thrombosis from a ruptured or eroded plaque, severe carotid stenosis causing hypoperfusion is highly predictive of stroke, although this effect may be time-limited. This apparent difference in event mechanism in the two arteries is interesting as is the difference in the rate of development of collaterals. Overall, the evidence shows that a clear relationship exists between disease in the coronary and carotid arteries, since conventional risk factors and the extent of stenosis and/or previous events emanating from one artery have a strong bearing on the prevalence of events in the other artery. Nevertheless, the exact correspondence between the two arteries is unclear, with sometimes contradictory study results. More research is needed to identify the full extent of risk factors for severe stenosis and cardio- or cerebral vascular events, among which, inflammatory biomarkers such as hs-CRP and prior vascular events are likely to play a key role. PMID:23218802

Jashari, Fisnik; Ibrahimi, Pranvera; Nicoll, Rachel; Bajraktari, Gani; Wester, Per; Henein, Michael Y

2013-04-01

159

Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis  

PubMed Central

Aim: To investigate the effects of the potassium-sparing diuretic amiloride on endothelial cell apoptosis during lipopolysaccharide (LPS)-accelerated atherosclerosis. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to LPS (100 ng/mL) in the presence of drugs tested. The activity of Na+/H+ exchanger 1 (NHE1) and calpain, intracellular free Ca2+level ([Ca2+]i), as well as the expression of apoptosis-related proteins in the cells were measured. For in vivo study, ApoE-deficient (ApoE?/?) mice were fed high-fat diets with 0.5% (w/w) amiloride for 4 weeks and LPS (10 ?g/mouse) infusion into caudal veins. Afterwards, atherosclerotic lesions, NHE1 activity and Bcl-2 expression in the aortic tissues were evaluated. Results: LPS treatment increased NHE1 activity and [Ca2+]i in HUVECs in a time-dependent manner, which was associated with increased activity of the Ca2+-dependent protease calpain. Amiloride (1?10 ?mol/L) significantly suppressed LPS-induced increases in NHE1 activity, [Ca2+]i. and calpain activity. In the presence of the Ca2+ chelator BAPTA (0.5 mmol/L), LPS-induced increase of calpain activity was also abolished. In LPS-treated HUVECs, the expression of Bcl-2 protein was significantly decreased without altering its mRNA level. In the presence of amiloride (10 ?mol/L) or the calpain inhibitor ZLLal (50 ?mol/L), the down-regulation of Bcl-2 protein by LPS was blocked. LPS treatment did not alter the expression of Bax and Bak proteins in HUVECs. In the presence of amiloride, BAPTA or ZLLal, LPS-induced HUVEC apoptosis was significantly attenuated. In ApoE?/? mice, administration of amiloride significantly suppressed LPS-accelerated atherosclerosis and LPS-induced increase of NHE1 activity, and reversed LPS-induced down-regulation of Bcl-2 expression. Conclusion: LPS stimulates NHE1 activity, increases [Ca2+]i, and activates calpain, which leads to endothelial cell apoptosis related to decreased Bcl-2 expression. Amiloride inhibits NHE1 activity, thus attenuates LPS-accelerated atherosclerosis in mice. PMID:23274414

Cui, Gui-mei; Zhao, Yu-xi; Zhang, Na-na; Liu, Zeng-shan; Sun, Wan-chun; Peng, Qi-sheng

2013-01-01

160

Contrasting Roles of Different Endoglin Forms in Atherosclerosis  

PubMed Central

Endoglin (also known as CD105 or TGF-? type III receptor) is a co-receptor involved in TGF-? signaling. In atherosclerosis, TGF-? signaling is crucial in regulating disease progression owing to its anti-inflammatory effects as well as its inhibitory effects on smooth muscle cell proliferation and migration. Endoglin is a regulator of TGF-? signaling, but its role in atherosclerosis has yet to be defined. This review focuses on the roles of the various forms of endoglin in atherosclerosis. The expression of the two isoforms of endoglin (long-form and short-form) is increased in atherosclerotic lesions, and the expression of the soluble forms of endoglin is upregulated in sera of patients with hypercholesterolemia and atherosclerosis. Interestingly, long-form endoglin shows an atheroprotective effect via the induction of eNOS expression, while short-form and soluble endoglin enhance atherogenesis by inhibiting eNOS expression and TGF-? signaling. This review summarizes evidence suggesting that the different forms of endoglin have distinct roles in atherosclerosis. PMID:25360074

Jang, Young-Saeng

2014-01-01

161

Prevalence and Correlates of Subclinical Atherosclerosis in Alaskan Eskimos  

PubMed Central

Background and Purpose The recent increase in clinical cardiovascular disease in Alaska Eskimos suggests that changes in traditional lifestyle may have adverse public health consequences. This study examines the prevalence of subclinical vascular disease and its relation to risk factors in Alaska Eskimos. Methods Participants in the population-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease risk factors and carotid ultrasound. Outcome variables were carotid intimal-medial thickness and presence and extent of atherosclerosis. Results In multivariate analyses, intimal-medial thickness and presence and extent of atherosclerosis were all associated with traditional cardiovascular disease risk factors but not dietary intake of omega-3 fatty acids. Rates of carotid atherosclerosis were higher than those reported in 2 large population-based US studies. Conclusions Alaska Eskimos have similar traditional risk factors for carotid atherosclerosis as other ethnic and racial populations but have higher prevalences of atherosclerosis, possibly attributable to higher rates of smoking. PMID:18617652

Cutchins, Alexis; Roman, Mary J.; Devereux, Richard B.; Ebbesson, Sven O.E.; Umans, Jason G.; Zhu, Jianhui; Weissman, Neil J.; Howard, Barbara V.

2009-01-01

162

Hyperhomocysteinemia potentiates hyperglycemia-induced inflammatory monocyte differentiation and atherosclerosis.  

PubMed

Hyperhomocysteinemia (HHcy) is associated with increased diabetic cardiovascular diseases. However, the role of HHcy in atherogenesis associated with hyperglycemia (HG) remains unknown. To examine the role and mechanisms by which HHcy accelerates HG-induced atherosclerosis, we established an atherosclerosis-susceptible HHcy and HG mouse model. HHcy was established in mice deficient in cystathionine ?-synthase (Cbs) in which the homocysteine (Hcy) level could be lowered by inducing transgenic human CBS (Tg-hCBS) using Zn supplementation. HG was induced by streptozotocin injection. Atherosclerosis was induced by crossing Tg-hCBS Cbs mice with apolipoprotein E-deficient (ApoE(-/-)) mice and feeding them a high-fat diet for 2 weeks. We demonstrated that HHcy and HG accelerated atherosclerosis and increased lesion monocytes (MCs) and macrophages (MØs) and further increased inflammatory MC and MØ levels in peripheral tissues. Furthermore, Hcy-lowering reversed circulating mononuclear cells, MC, and inflammatory MC and MC-derived MØ levels. In addition, inflammatory MC correlated positively with plasma Hcy levels and negatively with plasma s-adenosylmethionine-to-s-adenosylhomocysteine ratios. Finally, l-Hcy and d-glucose promoted inflammatory MC differentiation in primary mouse splenocytes, which was reversed by adenoviral DNA methyltransferase-1. HHcy and HG, individually and synergistically, accelerated atherosclerosis and inflammatory MC and MØ differentiation, at least in part, via DNA hypomethylation. PMID:25008174

Fang, Pu; Zhang, Daqing; Cheng, Zhongjian; Yan, Chenghui; Jiang, Xiaohua; Kruger, Warren D; Meng, Shu; Arning, Erland; Bottiglieri, Teodoro; Choi, Eric T; Han, Yaling; Yang, Xiao-Feng; Wang, Hong

2014-12-01

163

[Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].  

PubMed

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients. PMID:16792983

Páramo, José A; Beloqui, Oscar; Orbe, Josune

2006-05-27

164

Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice  

Microsoft Academic Search

Oxidative modification of low density lipoprotein (LDL) has been implicated in atherogenesis. Evidence consistent with this hypothesis includes the presence of oxidized lipids in atherosclerotic lesions, the newly discovered biological properties conferred on LDL by oxidation and the acceleration of atherogenesis by in vivo delivery of the gene for 15-lipoxygenase, an oxidizing enzyme present in atherosclerotic lesions. However, it is

Domenico Praticò; Rajendra K. Tangirala; Daniel J. Rader; Joshua Rokach; Garret A. FitzGerald

1998-01-01

165

Adipokines as a novel link between obesity and atherosclerosis  

PubMed Central

The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases. PMID:24936256

Yoo, Hye Jin; Choi, Kyung Mook

2014-01-01

166

Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis  

SciTech Connect

Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H{sub 2}S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H{sub 2}S and inflammatory processes. The role of H{sub 2}S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H{sub 2}S in atherosclerosis.

Qiao, Wang [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Chaoshu, Tang [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China) [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China); Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education (China); Hongfang, Jin, E-mail: jinhongfang51@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Junbao, Du, E-mail: junbaodu1@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)

2010-05-28

167

[B lymphocytes: a promising target to treat atherosclerosis?].  

PubMed

Atherosclerosis is a chronic inflammatory disease of the arterial wall. It is already well established that several immune cells (macrophages, T lymphocytes, etc.) modulate atherosclerosis progression whereas the role of the different subpopulations of B lymphocytes emerged only recently. B1 lymphocytes secrete protective IgM antibodies that act as scavenger of deleterious molecules whereas B2 lymphocytes probably worsen the disease by activating pro-inflammatory T lymphocytes. The outcome of these opposite functional properties of B lymphocytes on the evolution of arterial lesions may vary depending on their local environment during the different stages of the disease. In this review, we emphasize recent progresses in understanding the specific contribution of B lymphocytes to atherosclerosis and discuss the interest of targeting them to improve therapy. PMID:25311022

Hamze, Moustafa; Desmetz, Caroline; Guglielmi, Paul

2014-10-01

168

78 FR 77138 - Proposed Collection; 60-day Comment Request: The Atherosclerosis Risk in Communities Study (ARIC)  

Federal Register 2010, 2011, 2012, 2013

...Atherosclerosis Risk in Communities Study (ARIC) Summary: In compliance...Atherosclerosis Risk in Communities Study (ARIC),--Revised, National...The primary objectives of the study are to: (1) investigate factors...community levels of risk factors, medical care, and...

2013-12-20

169

SUSCEPTIBILITY TO ATHEROSCLEROSIS IN AORTAS AND CORONARY ARTERIES OF SWINE WITH VON WILLEBRAND'S DISEASE  

EPA Science Inventory

The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis ...

170

Human Genetic Evidence for Involvement of CD137 in Atherosclerosis  

PubMed Central

Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis. PMID:25032953

Soderstrom, Leif A; Gertow, Karl; Folkersen, Lasse; Sabater-Lleal, Maria; Sundman, Eva; Sheikine, Yuri; Goel, Anuj; Baldassarre, Damiano; Humphries, Steve E; de Faire, Ulf; Watkins, Hugh; Tremoli, Elena; Veglia, Fabrizio; Hamsten, Anders; Hansson, Goran K; Olofsson, Peder S

2014-01-01

171

Mice deficient in PKC? and apolipoprotein E display decreased atherosclerosis  

PubMed Central

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) ?II is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKC? in regulating key events linked to atherosclerosis and show that the aortas of apoE?/? mice display an age-dependent increase in PKC?II antigen in membranous fractions vs. C57BL/6 animals with a ?2-fold increase at age 6 wk and a ?4.5-fold increase at age 24 wk. Consistent with important roles for PKC? in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKC??/?/apoE?/? vs. apoE?/? mice by ?5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE?/? mice. Significant reduction in atherosclerosis of ?2-fold was observed in apoE?/? mice fed ruboxistaurin chow (PKC? inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKC?-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKC? may be beneficial in mitigating endothelial perturbation and atherosclerosis.—Harja, E., Chang, J. S., Lu, Y., Leitges, M., Zou, Y. S., Schmidt, A. M., Yan, S.-F. Mice deficient in PKC? and apolipoprotein E display decreased atherosclerosis. PMID:19036858

Harja, Evis; Chang, Jong Sun; Lu, Yan; Leitges, Michael; Zou, Yu Shan; Schmidt, Ann Marie; Yan, Shi-Fang

2009-01-01

172

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis  

PubMed Central

Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low-density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This suggests that a potential intervention on HO-1 or its byproducts may need to take into account any potential alteration in the status of Nrf2 activation. This article reviews the available evidence that supports the antiatherogenic role of HO-1 as well as the potential pathways and mechanisms mediating vascular protection. PMID:22833723

Araujo, Jesus A.; Zhang, Min; Yin, Fen

2012-01-01

173

Anti-inflammatory therapeutics for the treatment of atherosclerosis  

PubMed Central

Atherosclerosis is the primary cause of heart disease and stroke and is thus the underlying pathology of the leading causes of death in the western world. Although risk can be reduced by lowering lipid levels, the equally important contribution of inflammation to the development of cardiovascular disease is not adequately addressed by existing therapies. Here, we summarize the evidence supporting a role for inflammation in the pathogenesis of atherosclerosis, discuss agents that are currently in the clinic and provide a perspective on the challenges faced in the development of drugs that target vascular inflammation. PMID:21532566

Charo, Israel F.; Taub, Rebecca

2013-01-01

174

Perspectives and opportunities for nanomedicine in the management of atherosclerosis  

PubMed Central

The use of nanotechnology for medical purposes — nanomedicine — has grown exponentially over the past few decades. This is exemplified by the US Food and Drug Administration’s approval of several nanotherapies for various conditions, as well as the funding of nanomedical programmes worldwide. Although originally the domain of anticancer therapy, recent advances have illustrated the considerable potential of nanomedicine in the diagnosis and treatment of atherosclerosis. This Review elaborates on nanoparticle-targeting concepts in atherosclerotic disease, provides an overview of the use of nanomedicine in atherosclerosis, and discusses potential future applications and clinical benefits. PMID:22015921

Lobatto, Mark E.; Fuster, Valentin; Fayad, Zahi A.; Mulder, Willem J. M.

2013-01-01

175

Cooling the Fire of Atherosclerosis With Heat Shock Protein 27*  

PubMed Central

Decades of research have increased our understanding of the role and interplay between serum cholesterol, inflammation, and oxidative stress in the pathogenesis of atherosclerosis (1). Uptake and retention of low-density lipoprotein (LDL) by macrophages in the intima is dependent on adhesion molecules and inflammatory cytokines and amplified by oxidative stress. This hostile environment is toxic to endothelial and smooth muscle cells, which further hampers vascular homeostasis. These interrelated steps provide potentially fruitful therapeutic targets for the prevention and treatment of atherosclerosis. PMID:23747762

Weintraub, Neal L.; Rubinstein, Jack

2014-01-01

176

Lipid Rafts and Redox Regulation of Cellular Signaling in Cholesterol Induced Atherosclerosis  

PubMed Central

Redox mediated signaling mechanisms play crucial roles in the pathogenesis of several cardiovascular diseases. Atherosclerosis is one of the most important disorders induced mainly by hypercholesterolemia. Oxidation products and related signaling mechanisms are found within the characteristic biomarkers of atherosclerosis. Several studies have shown that redox signaling via lipid rafts play a significant role in the regulation of pathogenesis of many diseases including atherosclerosis. This review attempts to summarize redox signaling and lipid rafts in hypercholesterolemia induced atherosclerosis. PMID:22043207

Catalgol, Betul; Kartal Ozer, Nesrin

2010-01-01

177

De Novo Induction of Atherosclerosis by Chlamydia pneumoniae in a Rabbit Model  

Microsoft Academic Search

Chlamydia pneumoniae, a bacterial respiratory tract pathogen, has been associated with atherosclerosis in humans. C. pneumoniae infection of the respiratory tracts of rabbits fed a noncholesterol diet induced changes of atherosclerosis of the aorta in 6 (26.1%) of 23 animals after a single inoculum at 3 months. Multiple inocula given three times within 6 weeks resulted in grade III atherosclerosis

IGNATIUS W. FONG; BRIAN CHIU; ESTHER VIIRA; DAN JANG; JAMES B. MAHONY

1999-01-01

178

Promotion of Vascular Smooth Muscle Cell Growth by Homocysteine: A Link to Atherosclerosis  

Microsoft Academic Search

Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the

Jer-Chia Tsai; Mark A. Perrella; Masao Yashizumi; Chung-Ming Hsieh; Edgar Haber; Robert Schlegel; Mu-En Lee

1994-01-01

179

?-Secretase inhibitor reduces diet-induced atherosclerosis in apolipoprotein E-deficient mice  

PubMed Central

Atherosclerosis is a chronic inflammatory disease resulting from interactions between lipids, macrophages and arterial wall cells. The Notch signaling pathway is involved in the activation of macrophages in atherosclerotic lesions. This study examined whether pharmacological inhibition of Notch signaling using a ?-Secretase inhibitor (GSI) can reduce atherosclerotic lesion formation. Notch-related molecules were significantly increased in aortas from apolipoprotein E-deficient (ApoE?/?) mice. In particular, macrophages in the plaques showed strong expression of Notch1 and a downstream transcriptional factor, Hes-1. A GSI (LY411,575, 0.2, and 1.0 mg/kg/day) or vehicle control was then administered to ApoE?/? mice fed Western diet for 8 weeks before measuring the expression of Notch-related molecules. Systemic administration of GSI suppressed Notch signaling in vivo and reduced total plaque areas and fatty streak content in the aortic sinus in a dose-dependent manner without serious adverse effects. The GSI also suppressed the migratory activity of macrophages and reduced the expression of intercellular adhesion molecule-1, resulting in significantly decreased macrophage infiltration in the atherosclerotic plaques. These results provided new insight into the anti-atherogenic properties of GSI in Apo E?/? mice fed Western diet. PMID:19345673

Aoyama, Toru; Takeshita, Kyosuke; Kikuchi, Ryosuke; Yamamoto, Koji; Cheng, Xian Wu; Liao, James K.; Murohara, Toyoaki

2010-01-01

180

Fetal programming of atherosclerosis: Possible role of the mitochondria  

Microsoft Academic Search

Growing evidence indicates that being small size at birth from malnutrition is associated with an increased risk of developing type 2 diabetes (T2D), metabolic syndrome and cardiovascular disease in adulthood. Atherosclerosis is common to these aforementioned disorders, and oxidative stress and chronic inflammation are now considered as initiating events in its development, with endothelial cell dysfunction being an early, fundamental

Line Leduc; Emile Levy; Maurice Bouity-Voubou; Edgard Delvin

2010-01-01

181

Anti-inflammatory therapeutics for the treatment of atherosclerosis  

Microsoft Academic Search

Atherosclerosis is the primary cause of heart disease and stroke and is thus the underlying pathology of the leading causes of death in the western world. Although risk can be reduced by lowering lipid levels, the equally important contribution of inflammation to the development of cardiovascular disease is not adequately addressed by existing therapies. Here, we summarize the evidence supporting

Israel F. Charo; Rebecca Taub

2011-01-01

182

Evaluation of the biomechanics of atherosclerosis by acoustic microscopy  

NASA Astrophysics Data System (ADS)

Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

2001-07-01

183

CD36, a scavenger receptor implicated in atherosclerosis  

PubMed Central

CD36 is a membrane glycoprotein that is present on various types of cells, including monocytes, macrophages, microvascular endothelial cells, adipocytes and platelets. Macrophage CD36 participates in atherosclerotic arterial lesion formation through its interaction with oxidized low-density lipoprotein (oxLDL), which triggers signaling cascades for inflammatory responses. CD36 functions in oxLDL uptake and foam cell formation, which is the initial critical stage of atherosclerosis. In addition, oxLDL via CD36 inhibits macrophage migration, which may be a macrophage-trapping mechanism in atherosclerotic lesions. The role of CD36 was examined in in vitro studies and in vivo experiments, which investigated various functions of CD36 in atherosclerosis and revealed that CD36 deficiency reduces atherosclerotic lesion formation. Platelet CD36 also promotes atherosclerotic inflammatory processes and is involved in thrombus formation after atherosclerotic plaque rupture. Because CD36 is an essential component of atherosclerosis, defining the function of CD36 and its corresponding signaling pathway may lead to a new treatment strategy for atherosclerosis. PMID:24903227

Park, Young Mi

2014-01-01

184

Atherosclerosis in chronic kidney disease: the role of macrophages  

Microsoft Academic Search

Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe?\\/? mice

Valentina Kon; MacRae F. Linton; Sergio Fazio

2010-01-01

185

Progress and challenges in translating the biology of atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic disease of the arterial wall, and a leading cause of death and loss of productive life years worldwide. Research into the disease has led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke. Yet, despite these advances, we still lack definitive evidence to show that

Paul M Ridker; Göran K. Hansson; Peter Libby

2011-01-01

186

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

NASA Technical Reports Server (NTRS)

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

2000-01-01

187

Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias  

PubMed Central

A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer’s disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer’s disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer’s disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer’s disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43–67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and ?-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer’s disease–type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer’s disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology. PMID:23204143

Yarchoan, Mark; Xie, Sharon X.; Kling, Mitchel A.; Toledo, Jon B.; Wolk, David A.; Lee, Edward B.; Van Deerlin, Vivianna; Lee, Virginia M.-Y.; Trojanowski, John Q.; Arnold, Steven E.

2012-01-01

188

Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias.  

PubMed

A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer's disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer's disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer's disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer's disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43-67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and ?-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer's disease-type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer's disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology. PMID:23204143

Yarchoan, Mark; Xie, Sharon X; Kling, Mitchel A; Toledo, Jon B; Wolk, David A; Lee, Edward B; Van Deerlin, Vivianna; Lee, Virginia M-Y; Trojanowski, John Q; Arnold, Steven E

2012-12-01

189

TGF-?s and TGF-? receptors in atherosclerosis  

Microsoft Academic Search

Based on diverse evidence in animals and humans, it has been hypothesized that atherosclerosis, and other injury-induced hyperplasias such as restenosis, may result from a failure in endogenous inhibitory systems that normally limit wound repair and induce regression of wound repair cells. A key defect in one of these inhibitory pathways, the TGF-? system, has been identified and characterized in

Timothy A. McCaffrey

2000-01-01

190

TGF-betas and TGF-beta receptors in atherosclerosis  

Microsoft Academic Search

Based on diverse evidence in animals and humans, it has been hypothesized that atherosclerosis, and other injury-induced hyperplasias such as restenosis, may result from a failure in endogenous inhibitory systems that normally limit wound repair and induce regression of wound repair cells. A key defect in one of these inhibitory pathways, the TGF-beta system, has been identified and characterized in

T. A. McCaffrey

2000-01-01

191

Antithrombin III and Factor Xa Inhibitor in Atherosclerosis  

Microsoft Academic Search

75 patients with atherosclerosis divided into five disease groups (previous myocardial infarction and cerebral thrombosis, angina pectoris, transient ischemic attacks, arteriosclerosis obliterans) were studied and compared to 20 healthy subjects. Antithrombin III (AT III) concentration was determined by single radial immunodiffusion; AT III and factor Xa-inhibitor (Xa-I) activities were measured by amidolytic methods. No significant difference was found in any

R. Marra; L. Pagano; V. De Stefano; B. Bizzi

1983-01-01

192

Roles of microRNAs in atherosclerosis and restenosis  

PubMed Central

Atherosclerosis is commonly appreciated to represent a chronic inflammatory response of the vascular wall, and its complications cause high mortality in patients. Angioplasty with stent replacement is commonly performed in patients with atherosclerotic disease. However, the restenosis usually has a high incidence rate in angioplasty patients. Although the pathophysiological mechanisms underlying atherosclerosis and restenosis have been well established, new signaling molecules that control the progress of these pathologies have continuously been discovered. MicroRNAs (miRs) have recently emerged as a novel class of gene regulators that work via transcriptional degradation and translational inhibition or activation. Over 30% of genes in the cell can be directly regulated by miRs. Thus, miRs are recognized as crucial regulators in normal development, physiology and pathogenesis. AIterations of miR expression profiles have been revealed in diverse vascular diseases. A variety of 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 miRs. This review summarizes current research progress and knowledge on the roles of miRs in regulating vascular cell function in atherosclerosis and restenosis. These discoveries are expected to present opportunities for clinical diagnostic and therapeutic approaches in vascular diseases resulting from atherosclerosis and restenosis. PMID:22931291

2012-01-01

193

High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions  

Microsoft Academic Search

The concentration of high density lipoprotein-cholesterol (HDL-C) has been found consistently to be a powerful negative predictor of premature coronary heart disease (CHD) in human prospective population studies. There is also circumstantial evidence from human intervention studies and direct evidence from animal intervention studies that HDLs protect against the development of atherosclerosis. HDLs have several documented functions, although the precise

Philip Barter; John Kastelein; Alistair Nunn; Richard Hobbs

2003-01-01

194

Obstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis  

E-print Network

pharyngeal collapses occurring during sleep [1]. The upper airway closure could be complete, leadingObstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis Claire Arnaud1,2 , Maurice;31(1):113-25" DOI : 10.1007/s00281-009-0148-5 #12;2 ABSTRACT Obstructive sleep apnea (OSA) is a highly prevalent

Paris-Sud XI, Université de

195

Coronary Atherosclerosis and Alcohol Consumption Angiographic and Mortality Data  

Microsoft Academic Search

Objective—Moderate alcohol consumption is associated with reduced cardiovascular disease (CVD) risk. Whether this protection is based on a lesser degree of coronary atherosclerosis has not been established. Methods and Results—We studied 1676 men and 465 women consecutively undergoing coronary angiography. A score (ATS) was calculated by summing the percent lumen narrowing of all main vessels; alcohol consumption was quantitated by

Romana Femia; Andrea Natali; Antonio L'Abbate; Ele Ferrannini

2010-01-01

196

Corticosterone accelerates atherosclerosis in the apolipoprotein E-deficient mouse.  

PubMed

Chronic stress is an important risk factor for atherosclerosis, which is a chief process in the development of cardiovascular disease. Increased circulating levels of corticosterone have been documented in several animal models of chronic stress. However, it remains to be established whether corticosterone is sufficient to exacerbate atherosclerosis. To test this hypothesis, apolipoprotein E (ApoE)-deficient mice were fed a high-fat diet for 13 weeks with exposure to either corticosterone or vehicle in the drinking water (CORT and Con). Corticosterone treatment significantly increased atherosclerotic plaque area at the aortic root. Such exacerbation of atherosclerosis was accompanied by significantly lower levels of circulating white blood cells and serum interleukin-1? (IL-1?), and significantly elevated serum concentrations of total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (sd-LDL) in CORT mice when compared to Con mice. These findings demonstrate that corticosterone is sufficient to exacerbate atherosclerosis in vivo despite its anti-inflammatory properties and that this marked pro-atherogenic phenotype is primarily associated with increased dyslipidaemia. PMID:24468157

Okutsu, Mitsuharu; Lira, Vitor A; Higashida, Kazuhiko; Peake, Jonathan; Higuchi, Mitsuru; Suzuki, Katsuhiko

2014-02-01

197

Blood Flow Dynamics, Atherosclerosis and Bypass Graft Failure  

Microsoft Academic Search

Atherosclerosis occurs at reproducible sites in the arterial tree and intimal proliferation that leads to bypass graft occlusion also show a well-defined focal distribution. These observations have led to the hypothesis that local blood flow conditions, especially low or fluctuating shear stresses, are important in the development of both disorders. Basic research using both cell culture and animal models has

B. Lowell Langille; Matadial Ojha

1997-01-01

198

A novel dilute and shoot HPLC assay method for quantification of irbesartan and hydrochlorothiazide in combination tablets and urine using second generation C18-bonded monolithic silica column with double gradient elution.  

PubMed

Irbesartan (IRB) and hydrochlorothiazide (HCT) are angiotensin-II receptor antagonist and thiazide-class diuretic compounds, respectively, which are in use in the treatment of hypertension. A novel dilute-and-shoot HPLC assay method for simultaneous quantification of IRB and HCT in fixed-dose combination tablets and urine samples was described. The separation of IRB, HCT and agomelatine (internal standard) was carried out using a second generation C18-bonded monolithic silica column (Chromolith(®) High Resolution RP-18e, 100×4.6mm, Merck KGaA), utilizing both mobile phase and flow rate gradient elution programs. The analytes were detected at 230 nm wavelength using photodiode array detector within 24 minutes with high resolution, observing about 50 percent more peak capacity when using second generation C18-bonded monolithic silica column. Urine samples were introduced into the system effortlessly, with only filtration and subsequent dilution. Validation studies were performed according to the official recommendations of USP and ICH, and the developed method was successfully applied to pharmaceutical tablets and urine samples. PMID:24876066

Koyuturk, Sema; Can, Nafiz Oncu; Atkosar, Zeki; Arli, Goksel

2014-08-01

199

Prevalence of coronary atherosclerosis in patients with aortic valve replacement  

PubMed Central

Background Because of a high prevalence of coronary artery disease in patients with aortic valve disease, coronary angiography is recommended before aortic valve replacement. However, during the last three decades, a decline in mortality due to coronary heart disease has been observed in the general population in both Western Europe and the United States. It is unknown whether preoperative angiography is still mandatory in all patients. Aim To assess the prevalence of angiographically defined coronary artery disease in patients with aortic valve replacement and trends during a ten-year period. Methods We performed a retrospective cross-sectional study of patients undergoing aortic valve replacement between 1988 and 1998 in our institution. Patients with a history of coronary artery disease and patients younger than 25 years were excluded. Coronary atherosclerosis was defined as one or more coronary artery luminal stenosis of 50% or more on preoperative coronary angiography. Results During the study period 1339 patients had aortic valve replacement in our institution, data on 1322 (98%) were available for analysis. Previous coronary artery disease was documented in 124 patients (10%). After exclusion of 17 patients (no angiography), data on a total of 1181 patients were analysed. Coronary atherosclerosis was present in 472 patients (40%) on preoperative coronary angiography. Several well-known risk factors of ischaemic heart disease were associated with coronary atherosclerosis. The prevalence of angiographically defined coronary atherosclerosis varied between 30% and 50% per year. There was, however, no significant trend during the study period. Multivariate analyses, to adjust for potential differences in risk factors during the observation period, did not change this conclusion. Conclusions The prevalence of angiographically defined coronary artery disease in patients scheduled for aortic valve replacement is still high. From 1988 to 1998, no significant change was observed in angiographic measures of coronary atherosclerosis in patients with aortic valve replacement. Therefore, it is advised to perform coronary angiography before aortic valve surgery. ImagesFigure 1

Ottervanger, J.P.; Thomas, K.; Sie, T.H.; Haalebos, M.M.P.; Zijlstra, F.

2002-01-01

200

Regression of atherosclerosis in monkeys reduces vascular superoxide levels.  

PubMed

Superoxide (O2*-) in arteries may contribute to atherosclerosis in part by inactivation of nitric oxide. We hypothesized that regression of atherosclerosis in nonhuman primates is associated with a decrease in vascular NAD(P)H oxidase, decreased O2*- levels, and improved endothelium-dependent relaxation. Cynomolgus monkeys (n=28) were fed an atherogenic diet for 47+/-10 (mean+/-SE) months. In carotid arteries (containing advanced lesions), femoral arteries (moderate lesions), and saphena arteries (minimal lesions), we examined O2*- levels and vasomotor function. Compared with vessels from normal monkeys (n=8), O2*- levels (measured by lucigenin-enhanced chemiluminescence) were 3.3-fold higher in carotid, 1.7-fold higher in femoral, and not different in saphena arteries from atherosclerotic monkeys. Dihydroethidium staining also demonstrated increased O2*- levels throughout the vessel wall in femoral and carotid arteries from atherosclerotic monkeys. Components of the NAD(P)H oxidase (p22(phox) and p47(phox)) were increased in atherosclerotic arteries, and immunohistochemistry demonstrated colocalization primarily to areas of macrophage infiltration. Relaxation to acetylcholine was impaired in carotid and femoral, but not saphena, arteries from atherosclerotic monkeys. After 8 months of regression diet (n=9), serum cholesterol decreased to normal, and O2*- levels (basal and NAD(P)H-stimulated), as well as expression of NAD(P)H oxidase, returned toward normal. Relaxation to acetylcholine improved in femoral arteries, but not in the more diseased carotid arteries. We conclude that, in a primate model of moderately severe atherosclerosis and regression of atherosclerosis, changes in endothelial function are inversely related to O2*- and NAD(P)H oxidase levels. Reduction in vascular O2*- during regression of atherosclerosis may contribute to improvement in vasomotor function. PMID:11861415

Hathaway, Christopher A; Heistad, Donald D; Piegors, Donald J; Miller, Francis J

2002-02-22

201

Dexamethasone suppression test  

MedlinePLUS

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

202

Imaging of coronary atherosclerosis and identification of the vulnerable plaque  

PubMed Central

Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7

de Feyter, P.J.; Serruys, P. W.; Nieman, K.; Mollet, N.; Cademartiri, F.; van Geuns, R. J.; Slager, C.; van der Steen, A.F.W.; Krams, R.; Schaar, J.A.; Wielopolski, P.; Pattynama, P.M.T.; Arampatzis, A.; van der Lugt, A.; Regar, E.; Ligthart, J.; Smits, P.

2003-01-01

203

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis  

PubMed Central

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system. PMID:24395808

Kim, YongTae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

2014-01-01

204

Phospholipase A2 enzymes and the risk of atherosclerosis.  

PubMed

Certain members of the phospholipase A(2) superfamily of enzymes have established causal involvement in atherosclerosis, thus at least two groups of this family of enzymes have been considered potential candidates for the prevention of cardiovascular events. Recently completed experimental animal studies, human biomarker data, vascular imaging studies, and genome-wide atherosclerosis studies provide the rationale for proceeding with clinical outcome trials directed at inhibition of secretory phospholipase A(2) and lipoprotein-associated phospholipase A(2). A clinical trial with the sPLA(2) inhibitor varespladib methyl was recently terminated, while clinical trials with the Lp-PLA(2) inhibitor darapladib are being conducted in coronary heart disease patients. This article reviews the available experimental animal and human trial evidence that serve as the basis for the development of these two classes of phospholipase A(2) inhibitors. PMID:22802388

Rosenson, Robert S; Hurt-Camejo, Eva

2012-12-01

205

Impact of Ezetimibe on Atherosclerosis: Is the Jury Still Out?  

PubMed Central

Ezetimibe is a new lipid-lowering agent that inhibits intestinal absorption of dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol levels when used alone or in combination with statins. However, its effect on cardiovascular mortality remains unknown. We reviewed peer-reviewed published literature on the effect of ezetimibe on different phases of atherosclerosis. MEDLINE, EMBASE, BIOSIS, and other Web of Knowledge databases were searched for relevant abstracts and articles published in the English language that compared ezetimibe and statins as modulators of atherosclerosis. On the basis of the available evidence, ezetimibe appears to reduce inflammation when used in combination with statins, but its effect on endothelial function is mixed and less clear. The effect of ezetimibe on coronary disease progression or prevention of cardiovascular events is currently unknown. Use of ezetimibe as a second- or third-line agent to achieve low-density lipoprotein cholesterol treatment goals seems appropriate on the basis of the available evidence. PMID:19339654

Al Badarin, Firas J.; Kullo, Iftikhar J.; Kopecky, Stephen L.; Thomas, Randal J.

2009-01-01

206

Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges  

PubMed Central

The progression of atherosclerosis involves complex changes in the structure, composition and biology of the artery wall. Currently, only anatomical plaque burden is routinely characterized in living patients, whereas compositional and biological changes are mostly inaccessible. However, anatomical imaging alone has proven to be insufficient for accurate diagnostics of the disease. Multispectral optoacoustic tomography offers complementary data to anatomical methods and is capable of imaging both tissue composition and, via the use of molecular markers, the biological activity therein. In this paper we review recent progress in multispectral optoacoustic tomography imaging of atherosclerosis with specific emphasis on intravascular applications. The potential capabilities of multispectral optoacoustic tomography are compared with those of established intravascular imaging techniques and current challenges on the road towards a clinically viable imaging modality are discussed. PMID:23144663

Rosenthal, Amir; Jaffer, Farouc A; Ntziachristos, Vasilis

2012-01-01

207

Innate immunity and monocyte-macrophage activation in atherosclerosis  

PubMed Central

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review. PMID:21526997

2011-01-01

208

Inflammation and Diabetes-Accelerated Atherosclerosis: Myeloid Cell Mediators  

PubMed Central

Monocytes and macrophages respond to and govern inflammation by producing a plethora of inflammatory modulators, including cytokines, chemokines and arachidonic acid (C20:4)-derived lipid mediators. One of the most prevalent inflammatory diseases is cardiovascular disease, caused by atherosclerosis, and accelerated by diabetes. Recent research has demonstrated that monocytes/macrophages from diabetic mice and humans with type 1 diabetes show upregulation of the enzyme, acyl-CoA synthetase 1 (ACSL1), which promotes C20:4 metabolism, and that ACSL1 inhibition selectively protects these cells from the inflammatory and pro-atherosclerotic effects of diabetes, in mice. Increased understanding of the role of ACSL1 and other culprits in monocytes/macrophages in inflammation and diabetes-accelerated atherosclerosis offers hope for new treatment strategies to combat diabetic vascular disease. PMID:23153419

Kanter, Jenny E.; Bornfeldt, Karin E.

2012-01-01

209

Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta.  

PubMed

Considerable evidence supports the hypothesis that LDL oxidation plays an important role in atherosclerosis. Even though high melatonin doses inhibit LDL oxidation in vitro, the effect of melatonin on atherosclerosis has never been studied. We have demonstrated that the feeding of hypercholesterolemic mice with an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in the proximal aorta. These observations occur without detectable lipidic or glucidic phenotype alteration. Melatonin treatment increased highly the sensitivity of atherogenic lipoprotein to Cu(2+) and gamma-radiolysis generated oxyradical ex vivo oxidation during the fasting period. Moreover, these altered lipoproteins were less recognized by the LDL receptor metabolic pathway of murine fibroblasts while they transferred many more cholesteryl esters to murine macrophages. This study suggests that caution should be taken as regards high melatonin dosage in hypercholesterolemic patients. PMID:12051775

Tailleux, Anne; Torpier, Gérard; Bonnefont-Rousselot, Dominique; Lestavel, Sophie; Lemdani, Mohamed; Caudeville, Bernadette; Furman, Christophe; Foricher, Rachel; Gardes-Albert, Monique; Lesieur, Daniel; Rolando, Christian; Teissier, Elisabeth; Fruchart, Jean-Charles; Clavey, Véronique; Fievet, Catherine; Duriez, Patrick

2002-05-10

210

Chemokine receptor CCR5: from AIDS to atherosclerosis  

PubMed Central

There is increasing recognition of an important contribution of chemokines and their receptors in the pathology of atherosclerosis and related cardiovascular disease. The chemokine receptor CCR5 was initially known for its role as a co-receptor for HIV infection of macrophages and is the target of the recently approved CCR5 antagonist maraviroc. However, evidence is now emerging supporting a role for CCR5 and its ligands CCL3 (MIP-1?), CCL4 (MIP-1?) and CCL5 (RANTES) in the initiation and progression of atherosclerosis. Specifically, the CCR5 deletion polymorphism CCR5delta32, which confers resistance to HIV infection, has been associated with a reduced risk of cardiovascular disease and both CCR5 antagonism and gene deletion reduce atherosclerosis in mouse models of the disease. Antagonism of CCL5 has also been shown to reduce atherosclerotic burden in these animal models. Crucially, CCR5 and its ligands CCL3, CCL4 and CCL5 have been identified in human and mouse vasculature and have been detected in human atherosclerotic plaque. Not unexpectedly, CC chemokines have also been linked to saphenous vein graft disease, which shares similarity to native vessel atherosclerosis. Distinct roles for chemokine–receptor systems in atherogenesis have been proposed, with CCR5 likely to be critical in recruitment of monocytes to developing plaques. With an increased burden of cardiovascular disease observed in HIV-infected individuals, the potential cardiovascular-protective effects of drugs that target the CCR5 receptor warrant greater attention. The availability of clinically validated antagonists such as maraviroc currently provides an advantage for targeting of CCR5 over other chemokine receptors. PMID:21133894

Jones, KL; Maguire, JJ; Davenport, AP

2011-01-01

211

Platelets and their chemokines in atherosclerosis--clinical applications  

PubMed Central

The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis, i.e., stroke and myocardial infarction are definable but not the plaque burden. Platelet indices including platelet count and mean platelet volume (MPV) and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities, e.g., altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1b?, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation and atherosclerosis. PMID:25152735

von Hundelshausen, Philipp; Schmitt, Martin M. N.

2014-01-01

212

[Correction of disordered cerebral blood flow autoregulation in atherosclerosis].  

PubMed

The work deals with studying the parameters of autoregulation of the cerebral blood flow in a total of 127 patients subdivided into four groups. Clinical Group I consisted of thirty 45-to-70-year-old male patients (mean age 55.13 +/- 6.44 years) presenting with no signs of systemic atherosclerosis (CAD, chronic arterial insufficiency of the lower extremities, cerebrovascular insufficiency) or any other chronic diseases (chronic cardiac, pulmonary or renal insufficiency, chronic hepatitis, etc.). Clinical Group II comprised 32 patients diagnosed as having varying-degree chronic arterial insufficiency on the background of atherosclerosis obliterans of the lower-limb arteries (average age 57.46 +/- 5.15 years). Clinical Group III was composed of 30 patients presenting with different degrees of chronic cerebral ischaemia and having haemodynamically significant unilateral atherosclerotic lesions of the internal carotid artery (mean age 55.39 +/- 6.25 years), with the Control Group enrolling thirty-five 20-to-25-year-old volunteers. The findings of the work showed that the patients with atherosclerosis had significant impairments of the cerebral blood flow autoregulation, whose type and degree appeared to depend upon localization of the lesion. In the patients with peripheral atherosclerosis, a 10-day therapeutic course of intravenous administration of alpha-lipoic acid (Berlithion) at a dose of 600 mg daily could be used to correct disordered autoregulation of the cerebral vessels and may be considered from the position of preoperative preparation of such patients for reconstructive vascular interventions on the aorta and lower-limb arteries. Efficacy of alpha-lipoic acid (Berlithion) on the alterations in the cerebral blood flow autoregulation in patients presenting with haemodynamic stenosis of the internal carotid artery is insignificant, in connection with which such patients require surgical restoration of the patency of the major cerebral arteries. PMID:20092178

Fedin, A I; Kuznetsov, M R; Beresten', N F; Kuznetsova, V F; Kholopova, E A; Ibragimov, T M; Tugdumov, B V; Dubrovin, E E

2009-01-01

213

Statins Inhibit Rho Kinase Activity in Patients with Atherosclerosis  

PubMed Central

Background In addition to inhibiting cholesterol synthesis, statins (HMG-CoA reductase inhibitors) decrease the formation of isoprenoid intermediates required for the activation of key signaling pathways, including Rho/Rho kinase (ROCK). In experimental settings, statins inhibit ROCK and reverse vascular dysfunctions in atherosclerosis, independent of cholesterol reduction. It is not known whether statins inhibit ROCK activity in humans with atherosclerosis. Methods We investigated 35 patients with stable atherosclerosis in a randomized, double-blind study comparing treatment with high-dose (80 mg/d) or low-dose (10 mg/d) atorvastatin to placebo for 28 days. Blood samples for leukocyte ROCK activity, fasting lipids, and high-sensitivity C-reactive protein (hs-CRP) were obtained on days 0, 7, 14, and 28 after randomization and change over time with the 2 statin treatments relative to placebo was examined. Results Atorvastatin 80 mg/d reduced ROCK activity (p=0.002 vs. placebo). This decline was rapid and significant within 2 weeks of treatment. The inhibition of ROCK by atorvastatin (80 mg/d) remained significant even after controlling for changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (p=0.01). Furthermore, there was no correlation between changes in ROCK activity and changes in LDL-C (r=0.2, p=0.25) or triglycerides (r=0.1, p=0.55). There was a modest correlation between ROCK inhibition and change in hs-CRP among patients randomized to atorvastatin 80 mg/d (r=0.6, p=0.07). Conclusions These first-in-man findings demonstrate that high-dose atorvastatin rapidly inhibits the pro-atherogenic Rho/ROCK pathway, independent of cholesterol reduction. This inhibition may contribute to the clinical benefits of statins. Rho/ROCK may provide a useful therapeutic target in patients with atherosclerosis. PMID:19167712

Nohria, Anju; Prsic, Adnan; Liu, Ping-Yen; Okamoto, Ryuji; Creager, Mark A.; Selwyn, Andrew; Liao, James K.; Ganz, Peter

2008-01-01

214

Attenuation of the development of hypercholesterolemic atherosclerosis by thymoquinone  

PubMed Central

Thymoquinone (TQ), derived from Nigella sativa seed, is an antioxidant. The present study investigated whether TQ attenuates the development of atherosclerosis, and/or reduces the serum lipid levels and oxidative stress in rabbits. New Zealand white female rabbits were assigned to four groups of six animals each: group I, control; group II, 1% cholesterol diet; group III, 1% cholesterol plus TQ (10 mg/kg/day; through a nasogastric tube) diet; and group IV, 1% cholesterol plus TQ (20 mg/kg/day; through a nasogastric tube) diet. Blood samples were collected at baseline and after four and eight weeks on the experimental diets for measurement of serum lipids, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio and oxidative stress biomarkers (malondialdehyde [MDA] and protein carbonyls). At the end of the eight weeks, the aorta was removed for the assessment of atherosclerotic changes, MDA and protein carbonyls. Group II animals developed atherosclerosis (45%±11% of the intimal surface of aorta was covered with atherosclerotic plaques), which was associated with an increase in the serum TC, TG, LDL-C, HDL-C, TC/HDL-C, MDA and protein carbonyls. In group III, TQ decreased serum TC, LDL-C, MDA and protein carbonyls by 26%, 29%, 85% and 62%, respectively, and aortic MDA by 73%, which was associated with a 40% reduction of the development of aortic atherosclerosis. The higher dose of TQ in group IV had effects similar to the lower dose (group III), except that this dose further decreased serum TG. It is concluded that TQ attenuates hypercholesterolemic atherosclerosis and this effect is associated with a decrease in serum lipids and oxidative stress. PMID:22477447

Ragheb, Ahmed; Elbarbry, Fawzy; Prasad, Kailash; Mohamed, Adel; Ahmed, Mohamed S; Shoker, Ahmed

2008-01-01

215

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits  

PubMed Central

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

216

A Review of Atherosclerosis and Mathematical Transport Models  

Microsoft Academic Search

\\u000a The mechanisms and definitive predictive components involved within the clinical initiation and formation of atherosclerosis\\u000a remain elusive as of yet. Over the years, established fluid and mass transport theories and experimentally agreed upon vasoactive\\u000a agents have contributed towards a boom of predictive mathematical models concerning atherogenesis. This paper aims to elucidate\\u000a currently utilized theories available regarding initiation of atherosclerotic proliferation

B. Keller; F. Clubb Jr; G. Dubini

217

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects  

Microsoft Academic Search

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO\\/ISH criteria),

G Parrinello; D Colomba; P Bologna; A Licata; A Pinto; S Paterna; R Scaglione; G Licata

2004-01-01

218

Diagnosing atherosclerosis makes Nuclear Medicine a tissue imaging modality.  

PubMed

Atherosclerosis can be identified by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and is associated with cardiovascular events and all-cause mortality. Inflammation and classification appear jointly in the formation of atherogenesis. Arterial calcification has been also determined by CT, by (18)F-FDG PET and also in the last few years by (18)F-sodium fluoride (NaF) PET. Beheshti et al, have introduced a new concept for the detection of early molecular and cellular calcification in the atherosclerotic plaques of the heart and aorta, based upon the concept of global disease burden, which had been employed earlier using (18)F-FDG PET. Fluorine-18-NaF uptake in the heart and aorta increased significantly with advancing age. In a screening study involving 1,825 individuals, CT coronary artery calcification (CAC) was found to be common in healthy middle-aged individuals with a low Heart Score and, on the contrary, high-risk subjects very frequently did not have CAC. It is obvious that atherosclerosis appears early in life and also that the actual limits of atherosclerosis related to serious cardiovascular events should be determined by more research, since atherosclerosis is not the only cause of these episodes. It is possible that (18)F-NaF PET/CT may provide information about ongoing active molecular calcification in the plaque before calcification as a cause of cardiovascular episodes is detectable. Global molecular cardiovascular calcification, before becomes macroscopically visible, before it can be identified by CT, may be assessed by nuclear medicine procedures. (18)-NaF PET/CT is the first non-invasive imaging method to identify and localize high risk coronary plaque, a new frontier in nuclear cardiology. The above nuclear medicine diagnostic technique is a major and historical new application, for the diagnosis and the study of cardiovascular diseases, by which a certain tissue per se can be identified. PMID:24701591

Grammaticos, Philip C

2014-01-01

219

The genesis of atherosclerosis and risk factors: a review.  

PubMed

Atherosclerosis constitutes the most common medical and surgical problem. This can be manifested clinically as stroke, coronary artery disease, or peripheral vascular disease. In the present review the microscopic appearance of the normal arterial wall, the definition of atherosclerosis and the five theories of atherogenesis are described. These are: the lipid theory, the hemodynamic theory, the fibrin incrustation theory, the nonspecific mesenchymal hypothesis and the response to injury hypothesis. Based on the above theories the sequence of events in atherogenesis is analyzed. The classification of the atherosclerotic lesions according to Stary (types I-VI) and their characteristics appear in a table. The epidemiology and the role of the following risk factors are presented in detail: age, sex, lipid abnormalities, cigarette smoking, hypertension, diabetes mellitus, physical inactivity, alcohol consumption, obesity, and hemostatic factors. In addition, less common genetically determined associations like homocystinuria, Tangier disease, Hutchinson-Gilford syndrome (progeria), Werner's syndrome, radiation induced atherosclerosis and the implications of Chlamydia pneumoniae on the arterial wall are discussed. PMID:11228092

Tegos, T J; Kalodiki, E; Sabetai, M M; Nicolaides, A N

2001-02-01

220

PECAM-1 is a critical mediator of atherosclerosis  

PubMed Central

SUMMARY Atherosclerosis is a chronic inflammatory disease of large arteries in which lesion development preferentially occurs at vessel sites exposed to rapid changes in flow. We have previously shown that platelet endothelial cell adhesion molecule (PECAM-1), a surface receptor of the immunoglobulin superfamily, is involved in mechanosensing of rapid changes in flow. We wondered whether apolipoprotein E deficient (ApoE?/?) mice, predisposed to development of atheromas, would be protected from atherosclerosis by deficiency in PECAM-1. Using double knockout (DKO) mice for both PECAM-1 and ApoE (ApoE?/?/PECAM-1?/?) we found a significant reduction of sudanophilic lesions in their aortae compared to single knockout (SKO) (ApoE?/?/PECAM-1+/+) mice maintained on a high-fat Western diet. Immunostaining of aortic sinus cross sections demonstrated significantly lower ICAM-1 expression in DKO lesions compared with SKO lesions, and en face preparations of vessel regions subjected to disturbed and laminar flow showed less disruption of junctional connexin 43 in DKO than in SKO mice. Thus, PECAM-1 deficiency reduced the extent of lesions at the aortic arch and the aortic sinus, and lowered atherogenic indices. These results suggest that PECAM-1 is an important factor in the atherogenic changes seen in the ApoE-deficient mouse model and thus should be considered as a potential target for protection against atherosclerosis. PMID:19048083

Stevens, Hazel Y.; Melchior, Benoit; Bell, Kelly S.; Yun, Sujin; Yeh, Jiunn-Chern; Frangos, John A.

2008-01-01

221

Lasting monitoring of immune state in patients with coronary atherosclerosis  

NASA Astrophysics Data System (ADS)

Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

2007-02-01

222

Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis.  

PubMed

Alterations in DNA methylation patterns in peripheral blood leukocytes precede atherosclerotic lesion development in mouse models of atherosclerosis and have been linked to cardiovascular death in patients. The aim of this study is to investigate the long-term changes induced by WTD feeding on BM cells and the consequences for atherosclerosis susceptibility. Hereto, WTD BM or Chow BM was transplanted into LDLR KO mice on chow. BM from WTD BM recipient mice exhibited hypomethylation of CpG regions in the genes encoding Pu.1 and IRF8, key regulators of monocyte proliferation and macrophage differentiation. In agreement, in blood, the numbers of leukocytes were 40% (P<0.05) higher as a result of an increase in F4/80(+) monocytes (3.4-fold; P<0.01). An increase of CD11c(++) cells was also found (2.4-fold; P<0.05). Furthermore, spleens were enlarged, and the percentage of F4/80(+) cells expressing CD86 was induced (1.8-fold; P<0.01), indicating increased activation of splenic macrophages. Importantly, mice reconstituted with WTD BM showed a significant, 1.4-fold (P<0.05) increase in aortic root plaque size in the absence of changes in serum cholesterol. We conclude that WTD challenge induces transplantable epigenetic changes in BM, alterations in the hematopoietic system, and increased susceptibility to atherosclerosis. Manipulation of the epigenome, when used in conjunction with blood lipid reduction, could thus prove beneficial to treat cardiovascular disorders. PMID:25024399

van Kampen, Erik; Jaminon, Armand; van Berkel, Theo J C; Van Eck, Miranda

2014-11-01

223

Protective Role for Properdin in Progression of Experimental Murine Atherosclerosis  

PubMed Central

Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP) of complement is beneficial in LDLR?/? mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD) or high fat (HFD) Western type diets to newly generated LDLR?/? ProperdinKO (LDLR?/?PKO) and LDLR?/?PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR?/?PKO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA) were decreased in male LDLR?/?PKO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR?/? mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR?/?mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions. PMID:24667818

Byrne, Simon; Hughes, Timothy; Jayanthi, Archana; Guschina, Irina; Harwood, John; Cianflone, Katherine; Francis, Sheila

2014-01-01

224

Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis.  

PubMed

Advanced glycation end product (AGE) formation may contribute to the progression of atherosclerosis, particularly in diabetes. The present study explored atherosclerosis in streptozotocin-induced diabetic apolipoprotein E-deficient (apoE-/-) mice that were randomized (n = 20) to receive for 20 weeks no treatment, the AGE cross-link breaker ALT-711, or the inhibitor of AGE formation aminoguanidine (AG). A sixfold increase in plaque area with diabetes was attenuated by 30% with ALT-711 and by 40% in AG-treated mice. Regional distribution of plaque demonstrated no reduction in plaque area or complexity within the aortic arch with treatment, in contrast to the thoracic and abdominal aortas, where significant attenuation was seen. Diabetes-associated accumulation of AGEs in aortas and plasma and decreases in skin collagen solubility were ameliorated by both treatments, in addition to reductions in the vascular receptor for AGE. Collagen-associated reductions in the AGEs carboxymethyllysine and carboxyethyllysine were identified with both treatments. Diabetes was also accompanied by aortic accumulation of total collagen, specifically collagens I, III, and IV, as well as increases in the profibrotic cytokines transforming growth factor-beta and connective tissue growth factor and in cellular alpha-smooth muscle actin. Attenuation of these changes was seen in both treated diabetic groups. ALT-711 and AG demonstrated the ability to reduce vascular AGE accumulation in addition to attenuating atherosclerosis in these diabetic mice. PMID:15220206

Forbes, Josephine M; Yee, Louis Teo Loon; Thallas, Vicki; Lassila, Markus; Candido, Riccardo; Jandeleit-Dahm, Karin A; Thomas, Merlin C; Burns, Wendy C; Deemer, Elizabeth K; Thorpe, Susan R; Thorpe, Susan M; Cooper, Mark E; Allen, Terri J

2004-07-01

225

Fire Suppression and Response  

NASA Technical Reports Server (NTRS)

This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

Ruff, Gary A.

2004-01-01

226

Intracardiac calcification is a marker of generalized atherosclerosis.  

PubMed

Aortic valve calcification (AVC) and carotid artery calcification (CAC) are considered to be markers of generalized atherosclerosis. However, the role of intracardiac calcification (ICC) (valvular and perivalvular calcification) is unclear. The objective of this retrospective study was to analyze the relationship between ICC and CAC, risk factors, and clinical atherosclerotic disease. Risk factors included age, sex, diabetes mellitus, hypercholesterolemia, and hypertension; clinical atherosclerosis comprised stroke, coronary artery disease, and peripheral artery disease. Between January 1, 2001, and January 1, 2004, all consecutive patients were enrolled into the study who underwent both carotid ultrasonography and transthoracic echocardiography examinations within 2 months. Patients with renal failure, substantial aortic stenosis, and carotid artery occlusion were excluded. There were 320 patients (104 men; mean +/- SEM age, 66.6 +/- 0.76 years). Positive results on carotid ultrasonography are defined as any CAC. Patients were categorized as having mild, moderate, or severe CAC. Positive results on transthoracic echocardiography were defined as any ICC; AVC was defined as mitral anulus calcification (MAC) or both. Intracardiac calcification was found in 181 patients, AVC in 51 patients, MAC in 48 patients, and calcification of both structures in 82 patients. Using multiple logistic regression analysis, ICC (odds ratio, 1.9), age (10-year periods) (odds ratio, 2.0), and the presence of peripheral artery disease (odds ratio, 1.7) were independent predictors of CAC. Carotid ultrasonography results were positive in 227 patients. For CAC, the sensitivities of AVC, MAC, both, and any ICC were 52.4%, 52.0%, 33.5%, and 71.2%, respectively, and the specificities were 84.9%, 87.1%, 92.5%, and 78.5%, respectively. The extension of ICC as 0, 1 location (AVC or MAC) , or 2 locations (AVC and MAC) was associated with the severity of CAC (P < .001, tau = 0.42). There was no difference between patients with AVC vs patients with MAC in the presence of different stages of CAC (P = .62). Intracardiac calcification (MAC or AVC) is an independent predictor of CAC as a marker of atherosclerosis, although the lack of ICC does not rule out atherosclerosis. Intracardiac calcification is related to CAC, with high specificity. The extension of ICC is related to the severity of atherosclerosis. Based on our results, antiatherothrombotic therapy should be considered in patients with ICC even before obtaining a positive carotid ultrasonography result. PMID:17875954

Nemcsik, János; Farkas, Katalin; Kolossváry, Endre; Járai, Zoltán; Egresits, József; Borgulya, Gábor; Kiss, István; Lengyel, Mária

2007-01-01

227

Habitual fish intake and clinically silent carotid atherosclerosis  

PubMed Central

Background Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (? 0.90 mm), in non-diabetic participants. Methods Nine hundred-sixty-one (range of age: 18–89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. Results Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of???2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness???0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P?=?0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR?=?1.12; 95% CI?=?1.09-1.14), hypertension on pharmacologic treatment (OR?=?1.81; 95% CI?=?1.16-2.82), and pulse pressure (OR?=?1.03; 95% CI?=?1.01-1.04), while consuming ?2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR?=?0.46; 95% CI?=?0.26-0.80). Conclusions High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease. PMID:24405571

2014-01-01

228

The Role of Immunity and Inflammation in the Progression of Atherosclerosis in Patients With HIV Infection  

Microsoft Academic Search

Background and Purpose—The initial steps of atherosclerosis and the entry of HIV into the cell share similar biological mechanisms. Therefore, our hypothesis is that the progression of atherosclerosis in patients with HIV infection can be influenced by variations in genes implicated in both processes. Methods and Results—The progression of atherosclerosis over a 2-year follow-up period was measured as the combined

Blai Coll; Sandra Parra; Carlos Alonso-Villaverde; Gerard Aragones; Manuel Montero; Jordi Camps; Jorge Joven; Lluis Masana

2009-01-01

229

Atherosclerotic Risks from Chemicals: Part I. Toxicological Observations and Mechanisms of Atherosclerosis  

Microsoft Academic Search

.   Atherosclerosis is a common disease, primarily of the large arteries, that begins in childhood and progresses with advancing\\u000a age. Atherosclerosis leads to coronary heart disease, the major cause of death in the United States. Several risk factors\\u000a affect atherosclerosis, but high LDL cholesterol is the most important risk factor. In addition, high levels of lipoprotein\\u000a (a) appear to be

S. R. Basavaraju; T. D. Jones

1998-01-01

230

Non-invasive ultrasound monitoring of regional carotid wall structure and deformation in atherosclerosis  

E-print Network

Atherosclerosis is characterized by local remodeling of arterial structure and distensibility. Developing lesions either progress gradually to compromise tissue perfusion or rupture suddenly to cause catastrophic myocardial ...

Chan, Raymond C

2001-01-01

231

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis  

NASA Astrophysics Data System (ADS)

MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.

Hamada, Michito; Nakamura, Megumi; Tran, Mai Thi Nhu; Moriguchi, Takashi; Hong, Cynthia; Ohsumi, Takayuki; Dinh, Tra Thi Huong; Kusakabe, Manabu; Hattori, Motochika; Katsumata, Tokio; Arai, Satoko; Nakashima, Katsuhiko; Kudo, Takashi; Kuroda, Etsushi; Wu, Chien-Hui; Kao, Pei-Han; Sakai, Masaharu; Shimano, Hitoshi; Miyazaki, Toru; Tontonoz, Peter; Takahashi, Satoru

2014-01-01

232

Thought suppression and psychopathology  

Microsoft Academic Search

Wegner's seminal investigations of effects of thought suppression on later thought frequency have had a significant impact on recent approaches to understanding emotional disorders characterized by the occurrence of persistent, repetitive, unwanted thoughts. Thought suppression has now been implicated as a etiological and\\/or maintaining factor in depression, generalized anxiety disorder, specific phobia, posttraumatic stress disorder and obsessive–compulsive disorder. These developments

Christine Purdon

1999-01-01

233

Fluorescence spectroscopic detection of virus-induced atherosclerosis  

NASA Astrophysics Data System (ADS)

Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

1994-07-01

234

Influence of chronic exercise on carotid atherosclerosis in marathon runners  

PubMed Central

Objectives The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. Setting field study at Boston Marathon. Participants 42 qualifiers (mean age±SD: 46±13?years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12?years, n=21 women). Outcomes We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10?years Framingham risk, central arterial stiffness and SBP and cIMT. Results Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r?0.41; p<0.01) and Framingham risk score (all r?0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75?bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. Conclusions Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors. PMID:24531453

Taylor, Beth A; Zaleski, Amanda L; Capizzi, Jeffrey A; Ballard, Kevin D; Troyanos, Christopher; Baggish, Aaron L; D'Hemecourt, Pierre A; Dada, Marcin R; Thompson, Paul D

2014-01-01

235

The pigeon (Columba livia) model of spontaneous atherosclerosis.  

PubMed

Multiple animal models have been employed to study human atherosclerosis, the principal cause of mortality in the United States. Each model has individual advantages related to specific pathologies. Initiation, the earliest disease phase, is best modeled by the White Carneau (WC-As) pigeon. Atherosclerosis develops spontaneously in the WC-As without either external manipulation or known risk factors. Furthermore, susceptibility is caused by a single gene defect inherited in an autosomal recessive manner. The Show Racer (SR-Ar) pigeon is resistant to atherosclerosis. Breed differences in the biochemistry and metabolism of celiac foci cells have been described. For example, WC-As have lower oxidative metabolism but higher amounts of chondroitin-6-sulfate and nonesterified fatty acids compared with SR-Ar. Gene expression in aortic smooth muscle cells was compared between breeds using representational difference analysis and microarray analysis. Energy metabolism and cellular phenotype were the chief gene expression differences. Glycolysis and synthetic cell types were related to the WC-As but oxidative metabolism and contractile cell types were related to the SR-Ar. Rosiglitazone, a PPAR? agonist, blocked RNA binding motif (RBMS1) expression in WC-As cells. The drug may act through the c-myc oncogene as RBMS1 is a c-myc target. Proteomic tests of aortic smooth muscle cells supported greater glycosylation in the WC-As and a transforming growth factor ? effect in SR-Ar. Unoxidized fatty acids build up in WC-As cells because of their metabolic deficiency, ultimately preventing the contractile phenotype in these cells. The single gene responsible for the disease is likely regulatory in nature. PMID:25214557

Anderson, J L; Smith, S C; Taylor, R L

2014-11-01

236

The Role of Phospholipid Oxidation Products in Atherosclerosis  

PubMed Central

There is increasing clinical evidence that phospholipid oxidation products (Ox-PL) play a role in atherosclerosis. This review focuses on the mechanisms by which Ox-PL interact with endothelial cells, monocyte/macrophages, platelets, smooth muscle cells and HDL to promote atherogenesis. In the last few years major progress has been made in identifying these mechanisms. It has been recognized that Ox-PL promote phenotypic changes in these cell types that have long term consequences for the vessel wall. Individual Ox-PL responsible for specific cellular effects has been identified. A model of the configuration of bioactive truncated Ox-PL within membranes has been developed that demonstrates that the oxidized fatty acid moiety protrudes into the aqueous phase, rendering it accessible for receptor recognition. Receptors and signaling pathways for individual Ox-PL species are now determined and receptor independent signaling pathways identified. The effects of Ox-PL are mediated both by gene regulation and transcription independent processes. It has now become apparent that Ox-PL affects multiple genes and pathways some of which are pro-atherogenic and some are protective. However, at concentrations that are likely present in the vessel wall in atherosclerotic lesions, the effects promote atherogenesis. There have also been new insights on enzymes that metabolize Ox-PL and the significance of these enzymes for atherosclerosis. With the knowledge we now have on the regulation and effects of Ox-PL in different vascular cell types, it should be possible to design experiments to test the role of specific Ox-PL on the development of atherosclerosis. PMID:22935534

Lee, Sangderk; Birukov, Konstantin G.; Romanoski, Casey E.; Springstead, James R.; Lusis, Aldons J.; Berliner, Judith A.

2012-01-01

237

Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).  

PubMed

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans. PMID:23696447

Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

2013-11-01

238

Atherosclerosis and transit of HDL through the lymphatic vasculature  

PubMed Central

Key components of atherosclerotic plaque known to drive disease progression are macrophages and cholesterol. It has been widely understood, and bolstered by recent evidence, that the efflux of cholesterol from macrophage foam cells quells disease progression or even to promote regression. Following macrophage cholesterol efflux, cholesterol loaded onto HDL must be removed from the plaque environment. Here, we focus on recent evidence that the lymphatic vasculature is critical for the removal of cholesterol, likely as a component of HDL, from tissues including skin and the artery wall. We discuss the possibility that progression of atherosclerosis might in part be linked to sluggish removal of cholesterol from the plaque. PMID:23912686

Martel, Catherine; Randolph, Gwendalyn J.

2013-01-01

239

Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice[S  

PubMed Central

The formation of the atherosclerotic lesion is a complex process influenced by an array of inflammatory and lipid metabolism pathways. We previously demonstrated that NR4A nuclear receptors are highly induced in macrophages in response to inflammatory stimuli and modulate the expression of genes linked to inflammation in vitro. Here we used mouse genetic models to assess the impact of NR4A expression on atherosclerosis development and macrophage polarization. Transplantation of wild-type, Nur77?/?, or Nor1?/? null hematopoetic precursors into LDL receptor (LDLR)?/? recipient mice led to comparable development of atherosclerotic lesions after high-cholesterol diet. We also observed comparable induction of genes linked to M1 and M2 responses in wild-type and Nur77-null macrophages in response to lipopolysaccharides and interleukin (IL)-4, respectively. In contrast, activation of the nuclear receptor liver X receptor (LXR) strongly suppressed M1 responses, and ablation of signal transductor and activator of transcription 6 (STAT6) strongly suppressed M2 responses. Recent studies have suggested that alterations in levels of Ly6Clo monocytes may be a contributor to inflammation and atherosclerosis. In our study, loss of Nur77, but not Nor1, was associated with decreased abundance of Ly6Clo monocytes, but this change was not correlated with atherosclerotic lesion development. Collectively, our results suggest that alterations in the Ly6Clo monocyte population and bone marrow NR4A expression do not play dominant roles in macrophage polarization or the development of atherosclerosis in mice. PMID:23288947

Chao, Lily C.; Soto, Erin; Hong, Cynthia; Ito, Ayaka; Pei, Liming; Chawla, Ajay; Conneely, Orla M.; Tangirala, Rajendra K.; Evans, Ronald M.; Tontonoz, Peter

2013-01-01

240

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE?/? mice possibly via activated STAT3-mediated upregulation of tristetraprolin  

PubMed Central

Aim: To investigate the effects of the major component of high-density lipoprotein apolipoprotein A-I (apoA-I) on the development of atherosclerosis in LPS-challenged ApoE?/? mice and the underlying mechanisms. Methods: Male ApoE-KO mice were daily injected with LPS (25 ?g, sc) or PBS for 4 weeks. The LPS-challenged mice were intravenously injected with rAAV-apoA-I-GFP or rAAV-GFP. After the animals were killed, blood, livers and aortas were collected for biochemical and histological analyses. For ex vivo experiments, the abdominal cavity macrophages were harvested from each treatment group of mice, and cultured with autologous serum, then treated with LPS. Results: Chronic administration of LPS in ApoE?/? mice significantly increased the expression of inflammatory cytokines (TNF-?, IL-1?, IL-6, and MCP-1), increased infiltration of inflammatory cells, and enhanced the development of atherosclerosis. In LPS-challenged mice injected with rAAV-apoA-I-GFP, viral particles and human apoA-I were detected in the livers, total plasma human apoA-I levels were grammatically increased; HDL-cholesterol level was significantly increased, TG and TC were slightly increased. Furthermore, overexpression of apoA-I significantly suppressed the expression of proinflammatory cytokines, reduced the infiltration of inflammatory cells, and decreased the extent of atherosclerotic lesions. Moreover, overexpression of apoA-I significantly increased the expression of the cytokine mRNA-destabilizing protein tristetraprolin (TTP), and phosphorylation of JAK2 and STAT3 in aortas. In ex vivo mouse macrophages, the serum from mice overexpressing apoA-I significantly increased the expression of TTP, accompanied by accelerated decay of mRNAs of the inflammatory cytokines. Conclusion: ApoA-I potently suppresses LPS-induced atherosclerosis by inhibiting the inflammatory response possibly via activation of STAT3 and upregulation of TTP. PMID:23564081

Yin, Kai; Tang, Shi-lin; Yu, Xiao-hua; Tu, Guang-hui; He, Rong-fang; Li, Jin-feng; Xie, Di; Gui, Qing-jun; Fu, Yu-chang; Jiang, Zhi-sheng; Tu, Jian; Tang, Chao-ke

2013-01-01

241

Form to function: current and future roles for atherosclerosis imaging in drug development  

Microsoft Academic Search

There is a pressing need for robust imaging markers to assist in the development of drugs for the treatment of atherosclerosis. Conventional imaging methods provide quantitative and morphological data but may be inadequate for assessing a new generation of therapies that modify plaque biology directly. Here, we compare the main imaging modalities used to image atherosclerosis in the clinical-trial setting,

Alistair C. Lindsay; Robin P. Choudhury

2008-01-01

242

Serum magnesium concentrations in type 1 diabetic patients: Relation to early atherosclerosis  

Microsoft Academic Search

Hypomagnesemia and sub-clinical atherosclerosis are common in type 1 diabetic patients, and are especially common in poorly controlled and chronically treated diabetics. The aim of this study was to evaluate the relationships between serum magnesium (Mg) and intima-media thickness (IMT), and functions of common carotid artery (CCA), accepted as markers of early carotid atherosclerosis in type 1 diabetic patients. Serum

Mehmet Emre Atabek; Selim Kurtoglu; Ozgur Pirgon; Murat Baykara

2006-01-01

243

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias  

Microsoft Academic Search

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis

Stavros Apostolakis; Virginia Amanatidou; Demetrios A Spandidos

2010-01-01

244

Modification of Biochemical and Cellular Processes in the Development of Atherosclerosis by Red Wine  

Microsoft Academic Search

Atherosclerosis is commonly associated with unstable angina and acute myocardial infarction. It occurs as a result of a cascade of events caused by various environmental, dietary, genetic, and inflammatory factors. Different epidemiological studies have suggested that moderate amounts of red wine consumption reduce the risk of complications associated with atherosclerosis. This contention is further supported by a variety of experimental

HARJOT K. SAINI; Parambir Dhami; Yan-Jun Xu; Sukhinder Cheema; Amarjit Arneja; Naranjan Dhalla

245

Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).  

PubMed

An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk. PMID:18939649

Shrubsole-Cockwill, Alana; Wojnarowicz, Chris; Parker, Dennilyn

2008-09-01

246

The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus  

Microsoft Academic Search

The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we

Louise E Full; Cristina Ruisanchez; Claudia Monaco

2009-01-01

247

Enhanced susceptibility of cyclin kinase inhibitor p21 knockout mice to high fat diet induced atherosclerosis  

Microsoft Academic Search

Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in severe atherosclerosis in a mouse model. p21-\\/- and strain matched wild type mice were fed with high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides) in

Ashwani K Khanna

2009-01-01

248

75 FR 7482 - Submission for OMB Review; Comment Request; The Atherosclerosis Risk in Communities Study (ARIC)  

Federal Register 2010, 2011, 2012, 2013

...Atherosclerosis Risk in Communities Study (ARIC) Summary: Under the...Atherosclerosis Risk in Communities Study (ARIC). Type of Information...of participants in the ARIC study, review of their medical records...doctors and staff of hospitals and nursing homes. The annual...

2010-02-19

249

Atherosclerosis 203 (2009) 387394 Contents lists available at ScienceDirect  

E-print Network

July 2008 Available online 5 August 2008 Keywords: Atherosclerosis Angiotensin receptor blocker Shear (ESS). Methods: Twenty-four diabetic, hyperlipidemic swine were allocated into Early (n = 12) and Late the progression of atherosclerosis. Angiotensin II receptor type 1 blocking agents (ARBs), like Valsartan (V), may

Texas at Austin, University of

250

From genotype to phenotype in human atherosclerosis - recent findings  

PubMed Central

Purpose of review Since 2007, genome-wide association studies (GWAS) have led to the identification of numerous loci of atherosclerotic cardiovascular disease. The majority of these loci harbor genes previously not known to be involved in atherogenesis. In this review, we summarize the recent progress in understanding the pathophysiology of genetic variants in atherosclerosis. Recent findings Fifty-eight loci with P?atherosclerosis is limited and implicate a role of hitherto unknown mechanisms, such as epigenetic gene regulation in atherogenesis. PMID:24005217

Holdt, Lesca M.; Teupser, Daniel

2013-01-01

251

Coronary cardiac allograft vasculopathy versus native atherosclerosis: difficulties in classification.  

PubMed

Cardiac allograft vasculopathy is regarded as a progressive and diffuse intimal hyperplastic lesion of arteries and veins that leads to insidious vessel narrowing and to allograft ischemic disease, such as acute myocardial infarction or sudden cardiac death. The coronary lesions in transplanted hearts are considered as a particular type of arteriosclerosis with many similarities but also significant differences compared to native coronary atherosclerosis. It is particularly difficult for pathologists to systematically classify the lesions and to elucidate their origins, since over time, the allograft immune responses cause vascular pathology characterized by not only the onset of de novo fibrocellular lesions but also remodeling of already-existing native atherosclerotic lesions in the donor heart. Intraplaque hemorrhages, which result from newly formed leaky microvessels, may cause rapid increase of stenosis and generate a substrate for plaque destabilization. Comparing cardiac allograft vasculopathy from explanted hearts at autopsy with native coronary atherosclerosis from hearts removed at transplantation has revealed that ongoing intraplaque hemorrhages are also an important feature of cardiac allograft vasculopathy and may be important factors in the rapid progression of cardiac allograft vasculopathy. PMID:24807733

Angelini, Annalisa; Castellani, Chiara; Fedrigo, Marny; de Boer, Onno J; Meijer-Jorna, Lorine B; Li, Xiaofei; Valente, Marialuisa; Thiene, Gaetano; van der Wal, Allard C

2014-06-01

252

Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis.  

PubMed

Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellular uptake in RAW macrophages (fluorescent uptake of rhodamine) was studied on a fluorescence plate reader, while Gd-PS-induced alteration in T1 relaxivity was evaluated using a 1.5 T MRI scanner. RAW cells demonstrate PS-dependent uptake of across a range of concentrations (2, 6, 12, and 20%) in comparison to control liposomes with no PS (0%). In vivo performance of Gd-PS was evaluated in the ApoE(-/-) mouse model by collection of serial T1 weighted gradient echo MR images using an 11.7 T MRI system and revealed rapid and significant enhancement of the aortic wall that was seen for at least 4 h after injection. Gd-PS-enriched liposomes enhance atherosclerotic plaque and colocalize with macrophages in experimental atherosclerosis. PMID:19017616

Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P; Sen, Chandan K; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

2009-11-01

253

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?  

PubMed Central

MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernandez-Hernando, Carlos

2014-01-01

254

Monitoring SERS-based contrast agents in atherosclerosis experimental models  

NASA Astrophysics Data System (ADS)

There have been enormous progresses in developing a class of multimodal contrast agents, which combine MRI with optical imaging. Contrast agent targeting can provide enhanced diagnostic information, allowing differentiation between variable and stable atherosclerotic plaques. Recently an intensive efforts have been working on the development of contrast agents that can improve the ability to detect and characterize atherosclerosis in clinical and preclinical applications. Earlier studies on hyperlipidemic rabbits using in vivo MRI have shown accumulation of USPIOs in plaques with a high macrophage content that induces magnetic resonance (MR) signal changes correlated to the absolute iron content in the aortic arch. A potent new class of nanoparticles contrast agents have recently drawn much attention for its wide diverse diagnostic and potential therapeutic applications particularly in monitoring the inflammatory responses. In our previous studies we have investigated SPIO contrast agents uptakes in hepatic and spleen tissues taken from NZW rabbits. The scope of this work encompasses application of an emerging hybrid imaging modality, SERSbased nonlinear optical microscopy, in investigating atherosclerosis experimental models. In this work experiments are performed on contrast treated tissue sections taken from aortic arch of atherosclerotic animal model. Marked contrast enhancement has been observed in the treated aortic sections compared with the untreated control. The obtained images are compared with immunohistochemistry .The work presented can be promising for future studies on in vivo detection of macrophages in human plaques and early detection of atherosclerotic diseases.

Machtoub, Lina H.

2011-03-01

255

Conjugated linoleic acid modulation of risk factors associated with atherosclerosis  

PubMed Central

Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined. PMID:18718021

Nakamura, Yukiko K; Flintoff-Dye, Nichole; Omaye, Stanley T

2008-01-01

256

Effects of niacin on atherosclerosis and vascular function  

PubMed Central

Purpose of Review Niacin has been used for over fifty years in the management of atherosclerosis and is associated with improved patient outcomes. The routine use of niacin has been superseded in recent years with the advent of newer lipid-modulating interventions. Recently however, there has been a renewed interest in its use due to the appreciation of its many beneficial effects on atherosclerosis and endothelial function both ‘lipid-targeted’ and ‘pleiotropic’. This review will consider the effects of niacin in the setting of clinical trials and will critically evaluate proposed mechanisms of action. Recent Findings The identification of the GPR109A receptor has promoted a greater insight into niacin’s mechanism of action, with demonstrated beneficial effects on endothelial function and inflammation, in addition to its lipid modulation role. Summary Whether niacin itself is used routinely in the future will depend on the outcomes of two large outcome trials (AIM-HIGH and HPS2-THRIVE). In the future however, with even better understanding of niacin pharmacology, new drugs may be able to be engineered to capture aspects of niacin that capitalise on the benefits more specifically and also more selectively, to avoid troublesome side effects. PMID:21045681

Ruparelia, Neil; Digby, Janet E; Choudhury, Robin P

2011-01-01

257

Hemodynamic Predictors of Atherosclerosis in the Thoracic Aorta.  

PubMed

We sought to identify atherosclerotic plaques and measured flow parameters in the descending aorta (DA) of 83 consecutive patients (40 years and older) studied with transesophageal echocardiography. Patients with atherosclerotic plaques in the DA were older (68 +/- 10 vs 58 +/- 12 years [P = 0.0001]), had a higher proportion of spontaneous echo contrast in the DA (15/46 [33%] vs 3 of 37 [8%] P = 0.02), had larger aortic diameters (2.52 +/- 0.35 vs 2.37 +/- 0.36 cm [P = 0.06]), had a lower maximal velocity in the DA (54.2 +/- 21.5 vs 73.8 +/- 33.0 cm/sec [P = 0.02]), and had a lower calculated maximal shear rate (SR) (88.0 +/- 37.6 vs 129.0 +/- 67.0 sec(-1) [P = 0.002]). There was no significant difference between groups with respect to sex, hypertension, diabetes, total cholesterol, and smoking. In multivariate analysis only age (P = 0.002) and maximal SR (P = 0.03) were identified as independent predictors of atherosclerosis in the DA. We conclude that low SR is associated with aortic atherosclerosis. PMID:11175024

Sukernik, Mikhail R.; West, Oscar D.; Chittivelu, Babu; Vanderbush, Eric J.; Francis, Charles K.

1998-02-01

258

Aortic smooth muscle cell proteoglycan synthesis in relation to atherosclerosis  

SciTech Connect

Proteoglycans (PG) are implicated in atherogenesis by their effects on tissue permeability and cell proliferation and their interaction with plasma low density lipoproteins. Using the pigeon model in which an atherosclerosis-susceptible (WC) and -resistant (SR) breed can be compared, PG synthesis by cultured aortic smooth muscle cells was examined by the use of ({sup 35}S)-sodium sulfate and ({sup 3}H)-serine or ({sup 3}H)-glucosamine as labeling precursors. In both SR and WC cells, the majority of newly synthesized PG were secreted into the media. Chondroitin sulfate (CS) PG and dermatan sulfate (DS) PG were the major PG produced. Total PG production was consistently lower in WC compared to SR cultures due in part to reduce PG synthesis but also to degradation of newly synthesized PG. Since increased DS-PG accompanines atherosclerosis progression, experiments were designed to test the hypothesis that macrophages modulate smooth muscle cell metabolism to cause increase DS-PG production. Cultured WC aortic smooth muscle cells were exposed to the media of cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1 and the production of PG examined. Increasing concentration of conditioned media from both types of macrophages caused increased incorporation of {sup 35}S-sulfate into secreted PG, but no change in cell-associated PG. Lipopolysaccharide activation of P388D1 cells enhanced the effect.

Edwards, I.J.

1989-01-01

259

Cyclin-dependent kinase 9 may as a novel target in downregulating the atherosclerosis inflammation (Review)  

PubMed Central

Inflammation is a key component of atherosclerosis. Genes coding for inflammatory or anti-inflammatory molecules are considered good candidates for estimating the risk of developing atherosclerosis. Cyclin-dependent kinase 9 (CDK9), the kinase of positive transcription elongation factor b (P-TEFb), is crucial in the cell cycle and apoptosis. Previous studies have focused on its inhibition of immune cells for the resolution of inflammation. Considering the effects of inflammation in the pathogenicity of atherosclerosis, decreasing inflammation through the inhibition of CDK9 may be useful for the prognosis of atherosclerosis. The aim of this review was to examine whether inhibition of the CDK9 monocyte may affect the process of inflammation by acting on the cytokine secretion and interacting with endothelial cells (ECs). Thus, CDK9 may be a novel target for the diagnosis and therapy of atherosclerosis. PMID:25279144

HAN, YEMING; ZHAN, YANG; HOU, GUIHUA; LI, LI

2014-01-01

260

ADULT-ONSET ASTHMA IS ASSOCIATED WITH INCREASED CAROTID ATHEROSCLEROSIS AMONG WOMEN IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY  

PubMed Central

Some studies have suggested that asthma may be a risk factor for coronary heart disease and stroke, particularly in women. Child and adult-onset asthma differ according to inflammatory characteristics and gender distribution. We examined whether childhood-onset and adult-onset asthma were associated with carotid artery intima-media thickness (IMT) in men and women in the Atherosclerosis Risk in Communities (ARIC) study. In unadjusted analyses, the weighted mean far wall IMT thickness for women with history of adult-onset asthma was significantly greater than that of women without history of asthma (0.731mm vs. 0.681mm; p<0.0001) while IMT for women with history of childhood-onset asthma (IMT=0.684mm) did not differ substantially from non-asthmatic women. Mean IMT did not differ significantly according to asthma history among men. When the data were fitted to a linear model, the interaction between asthma status and gender was significant (p=0.006). After adjusting for age, race, BMI, smoking status, smoking pack years, diabetes, hypertension, physical activity, education level, and high and low density lipoprotein levels, the mean IMT difference between women with adult-onset asthma and no history of asthma was attenuated but remained significant (0.713mm vs. 0.687mm, p=0.008). In conclusion, adult-onset asthma but not child-onset asthma is associated with increased carotid atherosclerosis among women but not among men. PMID:17045272

Onufrak, Stephen; Abramson, Jerome; Vaccarino, Viola

2007-01-01

261

Neural correlates of thought suppression  

Microsoft Academic Search

The present report used functional magnetic resonance imaging (fMRI) to examine the neural correlates of thought suppression. Subjects were imaged while alternately (i) attempting to suppress a particular thought, (ii) attempting to suppress all thoughts, or (iii) thinking freely about any thought. Suppression of a particular thought, when compared to the free-thought control condition, revealed greater activation in the anterior

Carrie L. Wyland; William M. Kelley; C. Neil Macrae; Heather L. Gordon; Todd F. Heatherton

2003-01-01

262

Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages.  

PubMed

Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE(-/-) mice and its potential mechanism. ApoE(-/-) mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPAR?, LXR?, ABCA1 and ABCG1 as well as the transcriptional activity of PPAR?. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE(-/-) mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA. PMID:25187964

Wu, Chongming; Luan, Hong; Zhang, Xue; Wang, Shuai; Zhang, Xiaopo; Sun, Xiaobo; Guo, Peng

2014-01-01

263

Reduction of AMP-activated Protein Kinase Alpha 2 Increases Endoplasmic Reticulum Stress and Atherosclerosis In Vivo  

PubMed Central

Background Aberrant endoplasmic reticulum (ER) stress is associated with several cardiovascular diseases including atherosclerosis. The mechanism by which aberrant ER stress develops is poorly understood. This study investigated whether dysfunction of AMP-activated protein kinase (AMPK) causes aberrant ER stress and atherosclerosis in vivo. Methods and Results Human umbilical vein endothelial cells (HUVEC) and mouse aortic endothelial cells (MAEC) from AMPK-deficient mice were used to assess the level of ER stress using western blotting. Reduction of AMPK?2 expression significantly increased the level of ER stress in HUVEC. In addition, MAEC from AMPK?2 knockout mice (AMPK?2?/?) had higher expression of markers of ER stress and increased levels of intracellular Ca2+. These phenotypes were abolished by adenovirally overexpressing constitutively active AMPK mutants (Ad-AMPK-CA) or by transfecting sarco-endoplasmic reticulum calcium ATPase (SERCA). Inhibition of SERCA induced ER stress in endothelial cells. Furthermore, reduction of AMPK? expression suppressed SERCA activity. In addition, SERCA activity was significantly reduced concomitantly with increased oxidation of SERCA in MAEC from AMPK?2?/? mice. Both of these phenotypes were abolished by adenovirally overexpressing Ad-AMPK-CA. Furthermore, tempol, which restored SERCA activity and decreased oxidized SERCA levels, markedly reduced the level of ER stress in MAEC from AMPK?2?/? mice. Finally, oral administration of tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress, significantly reduced both ER stress and aortic lesion development in LDL receptor and AMPK?2 deficient mice. Conclusions These results suggest that AMPK functions as a physiological suppressor of ER stress by maintaining SERCA activity and intracellular Ca2+ homeostasis. PMID:20124121

Dong, Yunzhou; Zhang, Miao; Liang, Bin; Xie, Zhonglin; Zhao, Zhengxing; Asfa, Sima; Choi, Hyoung Chul; Zou, Ming-Hui

2010-01-01

264

Is there any relationship between Chlamydophila pneumoniae and coronary atherosclerosis among Iranians?  

PubMed Central

Background: Atherosclerosis is a coronary heart disease, andis the most common cause of death in the industrialized world. Some studies suggested that atherosclerosis may be triggered by infectious agents, mostly Chlamydophila pneumoniae. However, the role of C. pneumoniae in the pathogenesis of coronary atherosclerosis is still controversial. Objectives: This study was performed to evaluate whether there is a significant association between coronary artery atherosclerosis and C. pneumoniae by the polymerase chain reaction (PCR) method. Materials and Methods: This case-control study was carried out on formalin-fixed paraffin-embedded tissue biopsies of the coronary arteries obtained from 30 patients with coronary atherosclerosis and 30 subjects without atherosclerosis living in Northeast of Iran. All subjects' weight and height were determined, and the body mass index was calculated. We also reviewed the medical history and previous laboratory reports of patients. Deoxyribonucleic acid (DNA) was extracted, and C. pneumonia DNA was amplified and detected using PCR assay. Results: The age of the patients in the study group was from 18 to 50 years, and the male to female ratio was 5:1. Only oneout of the 30 coronary tissue samples had positive PCR for C. pneumoniae (3.3%), while it was negative for patients in the control group. Conclusions: This study showed that C. pneumoniae infection is not strongly associated with coronary artery atherosclerosis in Northeast of Iran. PMID:23661898

Sadeghian, Mohammad Hadi; Yazdi, Seyed Abbas Tabatabaee; Ayatollahi, Hossein; Keramati, Mohammad Reza; Ghazvini, Kiarash; Rezai, Ali Reza; Heidari, Nasrin; Sheikhi, Maryam; Shaghayegh, Gohar

2013-01-01

265

Prenatal Arsenic Exposure Alters Gene Expression in the Adult Liver to a Proinflammatory State Contributing to Accelerated Atherosclerosis  

PubMed Central

The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE?/?) mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE?/? mice exposed to 49 ppm arsenic in utero from gestational day (GD) 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND) 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). Gene ontology (GO) annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes containing SREBP1 binding sites also suggest pathways for diabetes mellitus and rheumatoid arthritis, both diseases that contribute to increased cardiovascular disease in humans. PMID:22719926

States, J. Christopher; Singh, Amar V.; Knudsen, Thomas B.; Rouchka, Eric C.; Ngalame, Ntube O.; Arteel, Gavin E.; Piao, Yulan; Ko, Minoru S. H.

2012-01-01

266

Gr-1+CD11b+ Immature Myeloid Cells (IMC) Promote Resistance of Pro-Inflammatory T Cells to Suppression by Regulatory T Cells in Atherosclerotic Apo E- Deficient Mice  

PubMed Central

Accumulating evidence indicates that both defects in Treg numbers and/or function as well as resistance of effector T cells to suppression may contribute to the development of human chronic inflammatory diseases. However, which mechanism involved in the progression of atherosclerosis remains unclear. In this study, we evaluated the production and function of CD4+ inflammatory and regulatory T cells in atherosclerosis-prone mice. We found that the hyperactivity and unresponsiveness to Treg-mediated suppression of inflammatory CD4+ T cells occurred in the progression of atherosclerosis, though Treg cells were present in very large numbers and fully functional. We further found that Gr-1+CD11b+ immature myeloid cells were significantly accumulated in atherosclerotic Apo E?/? mice, and they promoted resistance of inflammatory CD4+ T cells to Treg-mediated suppression in vitro and in vivo. we further confirmed that Gr-1+CD11b+ immature myeloid cells produced high level of interleukin 6 which was at least partially responsible for inducing unresponsiveness of inflammatory CD4+ T cells to suppression via activation of Jak/Stat signaling pathway. Taken together, these findings might provide new insights to explore potential targets for immune therapeutic intervention in atherosclerosis. PMID:25269085

Chen, Yulin; Jian, Ying; Liu, Minjie; Zhong, Liang; Zhang, Fang; Yang, Weifeng; Xu, Zhao; Chen, Guofan; Liu, Yuhua

2014-01-01

267

Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis  

PubMed Central

Extracellular matrix (ECM) within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavailability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dysregulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellular and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease. PMID:24474961

Ponticos, Markella; Smith, Barbara D.

2014-01-01

268

The downstream regulation of chemokine receptor signalling: implications for atherosclerosis.  

PubMed

Heterotrimeric G-protein-coupled receptors (GPCRs) are key mediators of intracellular signalling, control numerous physiological processes, and are one of the largest class of proteins to be pharmacologically targeted. Chemokine-induced macrophage recruitment into the vascular wall is an early pathological event in the progression of atherosclerosis. Leukocyte activation and chemotaxis during cell recruitment are mediated by chemokine ligation of multiple GPCRs. Regulation of GPCR signalling is critical in limiting vascular inflammation and involves interaction with downstream proteins such as GPCR kinases (GRKs), arrestin proteins and regulator of G-protein signalling (RGS) proteins. These have emerged as new mediators of atherogenesis by functioning in internalisation, desensitisation, and signal termination of chemokine receptors. Targeting chemokine signalling through these proteins may provide new strategies to alter atherosclerotic plaque formation and plaque biology. PMID:23690662

Patel, Jyoti; Channon, Keith M; McNeill, Eileen

2013-01-01

269

Mechanisms of Premature Atherosclerosis in Rheumatoid Arthritis and Lupus  

PubMed Central

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the two most common systemic autoimmune disorders, have both unique and overlapping manifestations. One feature they share is a significantly enhanced risk of atherosclerotic cardiovascular (CV) disease that significantly contributes to morbidity and mortality. The primary mechanisms that drive CV damage in these diseases remain to be fully characterized, but recent discoveries indicate that distinct inflammatory pathways and immune dysregulation characteristic of RA and SLE likely play prominent roles. This review focuses on analyzing the major mechanisms and pathways potentially implicated in the acceleration of atherothrombosis [**AU: Should this be atherosclerosis for consistency?**] and CV risk in SLE and RA, as well as in the identification of putative preventive strategies that may mitigate vascular complications in systemic autoimmunity. PMID:23020882

Kahlenberg, J. Michelle; Kaplan, Mariana J.

2014-01-01

270

Hydrogen sulfide and its modulation in arterial hypertension and atherosclerosis.  

PubMed

Apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H?S) is the third gaseous mediator in mammals. H?S is synthesized from L-cysteine by cystathionine ?-synthase (CBS), cystathionine ?-lyase (CSE), or by sequential action of alanine aminotransferase and 3-mercaptopyruvate sulfurtransferase. In the cardiovascular system, H?S is involved in the regulation of vascular tone and blood pressure, inhibits atherogenesis, and protects myocardium from ischemia-reperfusion injury. Recently, the first organic, water-soluble H?S donor, GYY4137, has been synthesized. In addition, H?S-releasing derivatives of several currently used drugs such as sildenafil, diclofenac, aspirin and mesalamine were obtained. Such compounds may be used in the future treatment of cardiovascular diseases. In this article, I describe the role of H?S in the regulation of blood pressure and in the pathogenesis of arterial hypertension and atherosclerosis which are two most common cardiovascular disorders. PMID:20545623

Be?towski, J; Jamroz-Wi?niewska, A; Tokarzewska, D

2010-10-01

271

Dynamic Aspects of Macrophage Polarization during Atherosclerosis Progression and Regression  

PubMed Central

It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1 (inflammatory)/M2 (anti-inflammatory) classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed.

Peled, Michael; Fisher, Edward A.

2014-01-01

272

Inhibitors of the 5-lipoxygenase pathway in atherosclerosis.  

PubMed

The inflammatory environment within the atherosclerotic lesion stimulates the 5-lipoxygenase pathway of arachidonic acid metabolism, leading to the biosynthesis of the potent lipid inflammatory mediators leukotrienes. The present review summarizes the components of this pathway; the enzymes 5-lipoxygenase (5-LO, ALOX5) with its activating protein, FLAP (ALOX5AP), LTA(4) hydrolase and LTC(4) synthase, as well as the receptors for leukotriene B(4) (BLT(1) and BLT(2)) and cysteinyl-leukotrienes (CysLT(1) and CysLT(2)), respectively. Genetic variations within the genes encoding these proteins have been associated with cardiovascular risk. Inhibiting the 5-lipoxygenase pathway through either leukotriene synthesis inhibitors or leukotriene receptor antagonists in experimental models of atherosclerosis has however generated contradictory results. Several inhibitors of the 5-lipoxygenase pathway are now evaluated in clinical trials of patients with cardiovascular disease. PMID:19754386

Bäck, Magnus

2009-01-01

273

Explosion suppression system  

DOEpatents

An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

Sapko, Michael J. (Finleyville, PA); Cortese, Robert A. (Pittsburgh, PA)

1992-01-01

274

Peculiarities of spectroscopic information of whole blood in atherosclerosis  

NASA Astrophysics Data System (ADS)

The coefficient of diffuse reflection and light transmission measurements in an optically thick layer of blood at atherosclerosis conditions under multiple scattering of light in the visual and nearest IR-spectra region (590 -900 nm) were measured for calculation of the absorption coefficients of the material of particles and surrounding medium K((lambda) ) and parameter Q (the latter parameter was defined by the sizes of erythrocytes and aggregates and by refraction coefficient of red cells relative to plasma at atherosclerosis). For the main quantitative spectroscopy of particles the K1((lambda) ) for known value of K((lambda) ) and the parameter Q determinations it is necessary to have the knowledge of relative volume part H occupied by particles. In the case of a high concentration of particles H >= 0.2 as it takes place in the blood the parameters Q and K((lambda) ) are in dependence of H (H - is hematocrit ration for the case of whole blood). It should be noted that spectroscopy of multiple scattering light can give some information out of main absorption bands with the higher accuracy and higher light scattering. The latter value provides the opportunity of determination of faint absorption bands which couldn't be achieved by other methods. The method proposed is characterized by absence of probe preparations, approach to in viva conditions, expressivity, and high informativity of each experiment. A many-fold investigation of the blood of healthy men in the spectral region 650 - 810 nm shows the electron spectrum of absorption of molecular hemoglobin hem is the most optically active blood spectra component K((lambda) ). The broadening of spectral investigations, as in short wave or long wave areas of the spectrum, by the use of multiple scattering methods for calculations of K((lambda) ) and Q((lambda) ) enlarges the number of chromophores studied.

Khairullina, Alphiya Y.; Oleinik, Tatiana V.; Yusupova, Lira B.; Prigoun, Natalia

1995-01-01

275

Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis  

PubMed Central

Atherosclerosis remains one of the most common causes of death in the United States and throughout the world because of the lack of early detection. Macrophage apoptosis is a major contributor to the instability of atherosclerotic lesions. Development of an apoptosis targeted high-density lipoprotein (HDL)-mimicking nanoparticle (NP) to carry contrast agents for early detection of vulnerable plaques and the initiation of preventative therapies that exploit the vascular protective effects of HDL can be attractive for atherosclerosis. Here, we report the construction of a synthetic, biodegradable HDL-NP platform for detection of vulnerable plaques by targeting the collapse of mitochondrial membrane potential that occurs during apoptosis. This HDL mimic contains a core of biodegradable poly(lactic-co-glycolic acid), cholesteryl oleate, and a phospholipid bilayer coat that is decorated with triphenylphosphonium (TPP) cations for detection of mitochondrial membrane potential collapse. The lipid layer provides the surface for adsorption of apolipoprotein (apo) A-I mimetic 4F peptide, and the core contains diagnostically active quantum dots (QDs) for optical imaging. In vitro uptake, detection of apoptosis, and cholesterol binding studies indicated promising detection ability and therapeutic potential of TPP-HDL-apoA-I-QD NPs. In vitro studies indicated the potential of these NPs in reverse cholesterol transport. In vivo biodistribution and pharmacokinetics indicated favorable tissue distribution, controlled pharmacokinetic parameters, and significant triglyceride reduction for i.v.-injected TPP-HDL-apoA-I-QD NPs in rats. These HDL NPs demonstrate excellent biocompatibility, stability, nontoxic, and nonimmunogenic properties, which prove to be promising for future translation in early plaque diagnosis and might find applications to prevent vulnerable plaque progression. PMID:23671083

Marrache, Sean; Dhar, Shanta

2013-01-01

276

Soluble TWEAK independently predicts atherosclerosis in renal transplant patients  

PubMed Central

Background Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects. Methods Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6?±?12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years). Results sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT. Conclusion sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients. PMID:23849432

2013-01-01

277

Chromosomal damage and atherosclerosis. A protective effect from simvastatin.  

PubMed

In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage. Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration. Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82+/-2.1 vs. 4.65+/-2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage. Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients. In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity. Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque. PMID:16483569

Pernice, Franco; Floccari, Fulvio; Caccamo, Chiara; Belghity, Nadia; Mantuano, Stefania; Pacilè, Maria Elisa; Romeo, Adolfo; Nostro, Lorena; Barillà, Antonio; Crascì, Eleonora; Frisina, Nicola; Buemi, Michele

2006-02-27

278

Vascular fluid mechanics, the arterial wall, and atherosclerosis.  

PubMed

Atherosclerosis, a disease of large- and medium-size arteries, is the chief cause of death in the United States and in most of the western world. Severe atherosclerosis interferes with blood flow; however, even in the early stages of the disease, i.e. during atherogenesis, there is believed to be an important relationship between the disease processes and the characteristics of the blood flow in the arteries. Atherogenesis involves complex cascades of interactions among many factors. Included in this are fluid mechanical factors which are believed to be a cause of the highly focal nature of the disease. From in vivo studies, there is evidence of hemodynamic influences on the endothelium, on intimal thickening, and on monocyte recruitment. In addition, cell culture studies have demonstrated the important effect of a cell's mechanical environment on structure and function. Most of this evidence is for the endothelial cell, which is believed to be a key mediator of any hemodynamic effect, and it is now well documented that cultured endothelial monolayers, in response to a fluid flow-imposed laminar shear stress, undergo a variety of changes in structure and function. In spite of the progress in recent years, there are many areas in which further work will provide important new information. One of these is in the engineering of the cell culture environment so as to make it more physiologic. Animal studies also are essential in our efforts to understand atherogenesis, and it is clear that we need better information on the pattern of the disease and its temporal development in humans and animal models, as well as the specific underlying biologic events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1522720

Nerem, R M

1992-08-01

279

Plasma cholesterol-induced lesion networks activated before regression of early, mature, and advanced atherosclerosis.  

PubMed

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (?80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr(-/-)Apob (100/100) Mttp (flox/flox)Mx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

Björkegren, Johan L M; Hägg, Sara; Talukdar, Husain A; Foroughi Asl, Hassan; Jain, Rajeev K; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-02-01

280

Plasma Cholesterol-Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis  

PubMed Central

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (?80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr?/?Apob100/100Mttpflox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

Bjorkegren, Johan L. M.; Hagg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aranzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-01-01

281

Social stress, visceral obesity, and coronary artery atherosclerosis in female primates.  

PubMed

Our previous work in cynomolgus monkeys demonstrated significant relationships between (i) social reorganization stress and visceral fat deposition, and (ii) central fat deposition and coronary artery atherosclerosis (CAA). Nevertheless, direct relationships between CAA and visceral fat have not been demonstrated in people or animals, nor have relationships among stress, visceral obesity, and CAA been observed within a single study. Here, we examine the hypothesis that visceral obesity provides a link between social stress and CAA. Subjects were 41 socially housed females that consumed an atherogenic diet for 32 months. Social behavior and ovarian function were continuously recorded; dexamethasone suppression tests, telemetered overnight heart rate, BMI, visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue were measured before necropsy. Females with high VAT:SAT were relatively subordinate, socially isolated, received more aggression and less grooming, desensitized to circulating glucocorticoids, had impaired ovarian function, higher heart rates late in the day, and more CAA than low VAT:SAT females. High-BMI females had higher heart rates than low-BMI females. Poor ovarian function in high VAT:SAT females is a novel observation suggesting the need for studies of fat distribution and ovarian function in women. The results of this study are the first to demonstrate a relationship between CAA and visceral obesity, and suggest that social stress may exacerbate CAA in part by increasing the ratio of visceral:subcutaneous fat mass in selected individuals susceptible to diet-induced CAA. Further studies are needed to understand the complex and multifactorial temporal relationship among relative visceral obesity, physiological stress responses, and CAA. PMID:19325545

Shively, Carol A; Register, Thomas C; Clarkson, Thomas B

2009-08-01

282

Triacetyl-3-hydroxyphenyladenosine, a derivative of cordycepin, attenuates atherosclerosis in apolipoprotein E-knockout mice.  

PubMed

The cholesterol-modulating, immune-regulating and anti-inflammatory properties of cordycepin are well documented. Here we examined the effects of triacetyl-3-hydroxyphenyladenosine (THPA), a derivative of cordycepin, on the development of atherosclerosis (AS) in apolipoprotein E-knockout (apoE(-/-)) mice. The atherosclerotic lesion formation displayed by the oil red O staining-positive area was reduced significantly in either the aortic root section or the whole aorta en face in THPA-administrated apoE(-/-) mice. Plasma analysis by enzymatic method or enzyme-linked immunosorbent assay (ELISA) showed that high-density lipoprotein-cholesterol (HDL-C) was decreased, whereas apolipoprotein A-I (apoA-I) levels were markedly increased by THPA. In addition, ELISA and spectrophotometric measurement showed that plasma levels of tumor necrosis factor-?, interleukin-1 and malondialdehyde were decreased in mice treated with THPA. Realtime polymerase chain reaction detection disclosed that the expression of several transporters involved in reverse cholesterol transport was induced by THPA, and the expression of hepatic ABCA1 and apoA-I, which play roles in the maturation of HDL-C, was also elevated in the THPA-treated groups. Moreover, THPA enhanced the expression of endothelial nitric oxide synthase (NOS), and reduced the expression of inducible NOS and lectin-like oxidized LDL receptor-1 in the aorta, suggesting that THPA can exert endothelial protection effects. In addition, the expression or activation of several proinflammatory factors in the aorta was suppressed by THPA. In conclusion, our results reveal the inhibitory effects of THPA on AS in apoE(-/-) mice. PMID:23239437

Zhao, Zhenmei; Song, Guohua; Tian, Hua; Yu, Yang; Tian, Xiangyu; Liu, Jia; Yao, Shutong; Luo, Tian; Qin, Shucun

2012-11-01

283

Mathematical Modeling of Immune Suppression  

Microsoft Academic Search

\\u000a Administered antibodies can suppress humoral immune response. Though there are two hypotheses explaining the suppression,\\u000a such as the epitope-masking and Fc-receptor mediated suppression, the epitope-masking hypothesis has garnered more supports.\\u000a To better understand how the immune suppression works and to gain a quantitative and qualitative insight, we developed the\\u000a first mathematical immune suppression model based on the epitope-masking hypothesis. However,

Dokyun Na; Doheon Lee

2005-01-01

284

[Gender peculiarities of development of atherosclerosis and impairment of brain oxygen supply in excessive body weight].  

PubMed

Aim of the given study was to elucidate special characteristics of mechanisms of development of atherosclerosis and supply of oxygen to the brain in overweight men and women. We included into this study 80 patients with multifocal atherosclerosis without history of myocardial infarction. We analyzed parameters of blood lipid composition, data of cerebral oxymetry, echocardiography, and central hemodynamics. We found gender linked differences in structural-functional parameters of myocardium and in mechanisms of progression of atherosclerosis which increased with increase of excess body weight. This was associated with differences in oxygen brain supply between men and women. PMID:23098399

Kamenskaia, O V; Levicheva, E N; Loginova, I Iu; Karpenko, A A; Starodubtsev, V B; Volkov, A M; Kliver, E E

2012-01-01

285

A historical perspective towards a non-invasive treatment for patients with atherosclerosis  

PubMed Central

The history of atherosclerosis and cardiovascular disease dates back to ancient times. From the teachings of Galen to the response-to-injury hypothesis of Russel Ross, we have now arrived at the concept of the vulnerable plaque. Next to the development of new treatment options for patients with atherosclerosis, also novel diagnostic imaging techniques have been developed to visualise the arterial wall and to characterise plaque composition. In this article the historical context of atherosclerosis and the attempts towards a noninvasive therapy for patients with atherosclerotic diseases are described. (Neth Heart J 2009;17:140-4.19421359) PMID:19421359

Slijkhuis, W.; Mali, W.; Appelman, Y.

2009-01-01

286

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes  

SciTech Connect

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields} A case-control study was conducted to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. {yields} Arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate atherosclerosis risk in individuals with high levels of arsenic in well water.

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China) [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China) [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China) [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China)] [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)] [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

287

Plasma suppression of beamstrahlung  

SciTech Connect

We investigate the use of a plasma at the interaction point of two colliding beams to suppress beamsstrahlung and related phenomena. We derive conditions for good current cancellation via plasma return currents and report on numerical simulations conducted to confirm our analytic results. 10 refs., 5 figs., 4 tabs.

Whittum, D.H.; Sessler, A.M.; Stewart, J.J.; Yu, S.S.

1988-06-01

288

Regulation of the renin-angiotensin system in coronary atherosclerosis: A review of the literature  

PubMed Central

Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis. PMID:18200812

Hammoud, Ramadan A; Vaccari, Christopher S; Nagamia, Sameer H; Khan, Bobby V

2007-01-01

289

Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses  

PubMed Central

Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated the possible association of H. cinaedi with atherosclerosis in vivo and in vitro. We found that H. cinaedi infection significantly enhanced atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice showed increased accumulation of neutrophils and F4/80+ foam cells, which was due, at least partly, to bacteria-mediated increased expression of proinflammatory genes. Although infection was asymptomatic, detection of cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H. cinaedi infection altered expression of cholesterol receptors and transporters in cultured macrophages and caused foam cell formation. Also, infection induced differentiation of THP-1 monocytes. These data provide the first evidence of a pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby justifying additional investigations of the possible role of enterohepatic Helicobacter spp. in atherosclerosis and cardiovascular disease. PMID:24732347

Khan, Shahzada; Rahman, H. N. Ashiqur; Okamoto, Tatsuya; Matsunaga, Tetsuro; Fujiwara, Yukio; Sawa, Tomohiro; Yoshitake, Jun; Ono, Katsuhiko; Ahmed, Khandaker Ahtesham; Rahaman, Md Mizanur; Oyama, Kohta; Takeya, Motohiro; Ida, Tomoaki; Kawamura, Yoshiaki; Fujii, Shigemoto; Akaike, Takaaki

2014-01-01

290

Thermal-based probe for testing endothelial dysfunction and possible implications for diagnosing atherosclerosis  

E-print Network

Endothelial dysfunction is a precursor to atherosclerosis. Thus, the vascular health of an individual can be assessed if endothelial dysfunction can be readily and unambiguously quantified. A thermal-based approach using ...

Lediju, Muyinatu A. (Muyinatu Adebisi)

2006-01-01

291

colleagues tackled only one particular facet of atherosclerosis. In reality, many factors --  

E-print Network

-- which might or might not depend on lipoprotein retention -- could also be operating at the same time of atherosclerosis, most patients suffering from the disease still die from cardiovascular complications. Thera- pies

Sethna, James P.

292

[Early coronary atherosclerosis in a malignant pheochromocytoma. Apropos of a case].  

PubMed

An observation of adrenergic myocarditis with clinical and electrical signs of coronary failure is reported. The patient had electrical and enzymatic manifestations of acute anteroseptal necrosis, complicated at the acute stage by complete atrioventricular block and fatal vasoplegic circulatory collapse. Post-mortem examination showed obstructive atherosclerosis of the anterior interventricular artery without anatomic signs of infarction. Pathogenesis of this coronary failure is discussed. In this case, functional coronary insufficiency produced by catecholamine release was associated with coronary atherosclerosis. PMID:6326281

Touze, J E; Monnier, A; Mardelle, T; Seka, R; Metras, D; Bertrand, E

1984-03-29

293

Atherosclerosis Pathophysiology and the Role of Novel Risk Factors: A Clinicobiochemical Perspective  

Microsoft Academic Search

Atherosclerosis is the root cause of the biggest killer of the 21st century. Mechanisms contributing to atherogenesis are multiple and complex. A number of theories—including the role of dyslipidemia, hypercoagulability, oxidative stress, endothelial dysfunction, and inflammation and infection by certain pathogens—have been propounded from time to time explain this complex phenomenon. Recently it has been suggested that atherosclerosis is a

V. Mallika; Binita Goswami; Medha Rajappa

2007-01-01

294

Measurement of arterial wall thickness as a surrogate marker for atherosclerosis  

Microsoft Academic Search

Large observational studies and atherosclerosis regression trials of lipid-modifying pharmacotherapy have established that intima-media thickness of the carotid and femoral arteries, as measured noninvasively by B-mode ultrasound, is a valid surrogate marker for the progression of atherosclerotic disease. To exploit fully the potential of ultrasound imaging in atherosclerosis research, standardized and strictly implemented imaging protocols should be used in both

Eric de Groot; G. Kees Hovingh; Albert Wiegman; Patrick Duriez; Andries J. Smit; Jean-Charles Fruchart; John J. P. Kastelein

2004-01-01

295

Atherosclerosis Impairs Endothelium-Dependent Vascular Relaxation to Acetylcholine and Thrombin in Primates  

Microsoft Academic Search

SUMMARY. To test the hypothesis that atherosclerosis impairs endothelium-dependent vascular relaxation, we examined the effect of the endothelium-dependent vasodilators acetylcholine and thrombin and the endothehum-independent vasodilator nitroglycerin on iliac arteries from normal cynomolgus monkeys and cynomolgus monkeys with diet-induced atherosclerosis. Rings of iliac artery were suspended in organ chambers at their optimal length for generating tension. After preconstriction with prostaglandin

Paul C. Freiman; Gordon G. Mitchell; Donald D. Heistad; Mark L. Armstrong; David G. Harrison

296

B-Lymphocyte Deficiency Increases Atherosclerosis in LDL Receptor-Null Mice  

Microsoft Academic Search

Objective—Atherosclerosis is an inflammatory disease characterized by innate and adaptive immune responses. We investigated the role of B cells and antibodies in the development of atherosclerosis in low density lipoprotein (LDL) receptor- deficient (LDLR\\/) mice. Methods and Results—Using wild-type and B cell- deficient mice as bone marrow donors, we were able to generate LDLR\\/ mice that possessed 1.0% of their

Amy S. Major; Sergio Fazio; MacRae F. Linton

2010-01-01

297

Estriol retards and stabilizes atherosclerosis through an NO-mediated system  

Microsoft Academic Search

Estriol (E3) has little effect on the female genitals. E3 is used in hormone replacement therapy, particularly in Europe and Japan, since it obviates the need for progestin administration. However, the effect of E3 on atherosclerosis has not been elucidated. In this study, we evaluated the effect of E3 on the progression of atherosclerosis in a rabbit model. Thirty-six rabbits

Hatsuyo Kano; Toshio Hayashi; Daigo Sumi; Hisako Matusi-Hirai; Taku Tsunekawa; Hidetoshi Endo; Akihisa Iguchi

2002-01-01

298

Preventing diabetes and atherosclerosis in sub-Saharan Africa: Should the metabolic syndrome have a role?  

Microsoft Academic Search

Obesity, hypertension, atherosclerosis, and type 2 diabetes mellitus are increasing in all regions of sub-Saharan Africa.\\u000a The metabolic syndrome is a valuable tool in predicting atherosclerosis and type 2 diabetes in populations in Europe and North\\u000a America. However, the applicability of the metabolic syndrome to African populations has not been studied. Prior to investing\\u000a scarce funds into diagnosing and treating

Omoye E. Imoisili; Anne E. Sumner

2009-01-01

299

Enhanced Progression of Early Carotid Atherosclerosis Is Related to Chlamydia pneumoniae (Taiwan Acute Respiratory) Seropositivity  

Microsoft Academic Search

Background— Chlamydia pneumoniae(Cp) infection has been associated with atherosclerosis and has been proposed as a possible additional cardiovascular risk factor. However, the relationship between Cp seropositivity and the progression of early carotid atherosclerosis is not unequivocally clarified. Methods and Results—We evaluated the association between serological detection of Cp IgG and\\/or IgA antibodies and the progression of the intima-media thickness (IMT)

Dirk Sander; Kerstin Winbeck; Jürgen Klingelhöfer; Thorleif Etgen; Bastian Conrad

300

An accelerated mouse model for atherosclerosis and adipose tissue inflammation  

PubMed Central

Background Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. Methods We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. Results After 12–16 weeks, LDLR-/- mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR-/- mice fed HFSC or HFC. Conclusion The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR-/- mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. PMID:24438079

2014-01-01

301

Atherosclerosis and Matrix Metalloproteinases: Experimental Molecular MR Imaging in Vivo  

PubMed Central

Purpose: To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947. Materials and Methods: The Animal Care and Use Committee approved all experiments. P947 was synthesized by attaching a gadolinium chelate (1,4,7,10-tetraazacyclododecane-N,N?,N?,N?-tetraacetic acid) to a peptide that specifically binds MMPs. Scrambled form of P947 (P1135) was synthesized by replacing the targeting moiety of P947 with a scrambled peptide lacking the ability to bind MMPs. P947, P1135, and gadoterate meglumine were injected into atherosclerotic apolipoprotein E–deficient and wild-type mice. The aortic MR imaging enhancement produced by the contrast agents was measured at different times and was compared by using one-way analysis of variance. MMP expression was investigated in the aortas by using MMP immunostaining and in situ MMP zymography. A fluorescent form of P947 (Eu-P947) was synthesized to compare the in vivo distribution of the contrast agent (Eu-P947) with specific MMP immunofluorescent staining. Results: MMP-targeted P947 facilitated a 93% increase (P < .001) in MR image signal intensity (contrast-to-noise ratio [CNR], 17.7 compared with 7.7; P < .001) of atherosclerotic lesions in vivo. Nontargeted P1135 (scrambled P947) provided 33% MR image enhancement (CNR, 10.8), whereas gadoterate meglumine provided 5% (CNR, 6.9). Confocal laser scanning microscopy demonstrated colocalization between fluorescent Eu-P947 and MMPs in atherosclerotic plaques. Eu-P947 was particularly present in the fibrous cap region of plaques. Conclusion: P947 improved MR imaging for atherosclerosis through MMP-specific targeting. The results were validated and provide support for further assessment of P947 as a potential tool for the identification of unstable atherosclerosis. © RSNA, 2009 PMID:19224894

Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Amirbekian, Smbat; Hyafil, Fabien; Vucic, Esad; Sirol, Marc; Weinreb, David B.; Le Greneur, Soizic; Lancelot, Eric; Corot, Claire; Fisher, Edward A.; Galis, Zorina S.; Fayad, Zahi A.

2009-01-01

302

Lp-PLA2 Inhibition--The Atherosclerosis Panacea?  

PubMed Central

Based on the complex pathophysiology of atherosclerosis, a large number of biomarkers that relate to lipids, inflammation, immunity, thrombosis and hemostasis, have been investigated experimentally, in epidemiologic studies and in clinical trials. Interest focuses on their potential role to aid in risk stratification, as possible surrogate markers of atherosclerosis, and potential targets for therapy. More recently, one lipid associated biomarker, lipoprotein-associated phospholipase A2 (Lp-PLA2), has gained considerable interest. In addition to a plausible pathophysiological role by generating pro-inflammatory and pro-atherogenic compounds from oxidized LDL in the vessel wall, there is a large, fairly consistent epidemiological database indicating that increased levels of Lp-PLA2 mass or activity are associated with increased risk for cardiovascular outcomes; such data further suggest that it might improve risk stratification. In addition, clinical studies indicate that increased Lp-PLA2 levels are associated with endothelial dysfunction. Moreover, it may also serve as an interesting therapeutic target, since a specific inhibitor of the enzyme is available with promising animal data and initial positive data in humans. Recent experimental data from a hyperlipidemic diabetic pig model strongly suggest that increased Lp-PLA2 in the vessel wall is associated with a more vulnerable plaque phenotype which can be modulated by inhibiting Lp-PLA2 activity. A biomarker study in more than 1,000 patients with CHD over three months has demonstrated a positive effect on various inflammatory molecules. In addition, an imaging study using IVUS based modalities (greyscale, virtual histology, and palpography) together with a panel of biomarkers (IBIS-2) has been done in more than 300 patients with CHD treated over 12 months and results indicate that the progression of the necrotic core of the plaque can be retarded. Inhibition of the pro-atherogenic and pro-inflammatory effects of Lp-PLA2 may therefore contribute to decrease the residual risk in high risk patients already on polypharmacotherapy. This hypothesis is now being tested in two large phase 3 clinical trials. Thus, Lp-PLA2 indeed may represent a biomarker and a promising target for intervention.

Karakas, Mahir; Koenig, Wolfgang

2010-01-01

303

ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association.  

PubMed

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p<0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects. PMID:24739810

Riccioni, Graziano; Scotti, Luca; D'Orazio, Nicolantonio; Gallina, Sabina; Speziale, Giuseppe; Speranza, Lorenza; Bucciarelli, Tonino

2014-01-01

304

ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association  

PubMed Central

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p < 0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p < 0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects. PMID:24739810

Riccioni, Graziano; Scotti, Luca; D’Orazio, Nicolantonio; Gallina, Sabina; Speziale, Giuseppe; Speranza, Lorenza; Bucciarelli, Tonino

2014-01-01

305

Pressure suppression containment system  

DOEpatents

A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

Gluntz, D.M.; Townsend, H.E.

1994-03-15

306

Denervation suppresses gastric tumorigenesis.  

PubMed

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor-mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

Zhao, Chun-Mei; Hayakawa, Yoku; Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B; Andersen, Gøran T; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A; Renz, Bernhard W; Sandvik, Arne K; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D; Kaneko, Kazuhiro; Fox, James G; Wang, Timothy C; Chen, Duan

2014-08-20

307

Pentoxifylline Decreases Serum Level of Adhesion Molecules in Atherosclerosis Patients  

PubMed Central

Background: Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Methods: Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Results: Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Conclusion: Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels. PMID:24375159

Mohammadpour, Amir Hooshang; Falsoleiman, Homa; Shamsara, Jamal; Abadi, Ghazaleh Allah; Rasooli, Ramin; Ramezani, Mohammad

2014-01-01

308

Comparison of automatic atherosclerosis identification methods on MR imagery  

NASA Astrophysics Data System (ADS)

Magnetic resonance imaging (MRI) provides excellent soft tissue contrast enabling the non-invasive visualization of soft lissue diseases. The quantification of tissues distinguishable in MR images significantly increases the diagnostic information available to physicians. New 3-D display workstations are available that can also make use of the tissue characteristics to generate clinically useful views of a patient. While simple tissue selection methods work with computed tomography (CT) images these same methods usually do not work with MR images. Several feasibility studies of tissue classification methods have been performed on MR images but few comparative studies of these methods have been published and little work is available on the best statistical model of tissues in MIRI. We have developed a novel method for the identification and quantification of soft tissues from MRI atherosclerosis in particular. This project is part of our work on the development of tissue characterization and identification tools to facilitate soft tissue disease diagnosis and evaluation utilizing MR imagery. Several supervised pattern recognition methods were investigated for tissue identification in MR images such as a Fisher linear discriminant and a minimum distance to the means classifier. For tissue in vivo adequate histology can be difficult to collect. We used cluster analysis methods to generate the necessary training information. ISODATA was modified to use hierarchical stopping rules to determine the true number of tissues in the images. This new method was

Carman, Charles S.; Merickel, Michael B.

1990-07-01

309

Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.  

PubMed

Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE(-/-)) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased I?B phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-? and IL-6. Celastrol reduced atherosclerotic plaque size in apoE(-/-) mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE(-/-) mice via inhibiting LOX-1 and oxidative stress. PMID:23799016

Gu, Lei; Bai, Wenli; Li, Sha; Zhang, Yuqing; Han, Yi; Gu, Yue; Meng, Guoliang; Xie, Liping; Wang, Jing; Xiao, Yujiao; Shan, Liyang; Zhou, Suming; Wei, Lei; Ferro, Albert; Ji, Yong

2013-01-01

310

Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage  

Microsoft Academic Search

Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins (LDL) receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotein E-deficient (apoE?\\/?) mice was investigated. In apoE?\\/? mice, berberine induced in vivo foam cell formation and promoted atherosclerosis development.

Ke Li; Wenqi Yao; Xiudan Zheng; Kan Liao

2009-01-01

311

Decreased Naive and Increased Memory CD4+ T Cells Are Associated with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis  

PubMed Central

Background Adaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis. Methods and Findings We examined cross-sectional relationships of circulating CD4+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4+ naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ?0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population [?-Coefficient (95% confidence interval (CI)) ?=?0.20 (0.03, 0.37)]. Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans [memory: ??=? 0.02 (0.006, 0.04); naive: ??=??0.02 (?0.004, ?0.03)]. Conclusions These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4+ T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis. PMID:24009662

Olson, Nels C.; Doyle, Margaret F.; Jenny, Nancy Swords; Huber, Sally A.; Psaty, Bruce M.; Kronmal, Richard A.; Tracy, Russell P.

2013-01-01

312

Leukotriene A4 Hydrolase Haplotype, Diet and Atherosclerosis: A Twin Study  

PubMed Central

Objective Atherosclerosis is an inflammatory process resulting from the interaction between genetic and environmental factors. Leukotrienes are inflammatory mediators generated from arachidonic acid, and genetic polymorphisms involved in leukotriene metabolism are implicated in atherosclerosis. The objectives of this study are to examine whether genetic variants in key leukotriene enzymes are associated with atherosclerosis, and whether dietary intake of competing leukotriene substrates modifies the effect of leukotriene variants on atherosclerosis. Methods Atherosclerosis was assessed by common carotid intima-media thickness (IMT) using ultrasound. Sequence variants within arachidonate 5-lipoxygenase activating protein (ALOX5AP) and leukotriene A4 hydrolase (LTA4H) genes were analyzed with 32 single nucleotide polymorphisms (SNPs) in 169 Caucasian twin pairs from the Vietnam Era Twin Registry. The associations between genetic polymorphisms and carotid atherosclerosis, and gene × diet interactions were examined by generalized estimating equation controlling for potential confounders. Results A six-SNP haplotype in LTA4H, designated HapE, was significantly associated with carotid IMT after adjusting for known coronary risk factors. Twins carrying HapE had a much lower IMT compared to twins not carrying (695 ?m vs. 750 ?m, p=0.0007). Moreover, dietary intake of polyunsaturated fatty acids strongly augmented the cardioprotective effect of HapE among those with this haplotype but not those without, suggesting a haplotype × diet interaction (Interaction PHapE × n-3 = 0.03, PHapE × n-6 = 0.015). Conclusion We identified a novel leukotriene haplotype that appears to be protective towards subclinical atherosclerosis. This association is modified by dietary intake of polyunsaturated fatty acids. PMID:23153620

Zhao, Jinying; Goldberg, Jack; Vaccarino, Viola

2012-01-01

313

Urotensin II Promotes Atherosclerosis in Cholesterol-Fed Rabbits  

PubMed Central

Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P?=?0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P?=?0.005), 11% in the thoracic aorta (P?=?0.054) and 18% in the abdominal aorta (P?=?0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits. PMID:24747943

Li, Yafeng; Zhao, Sihai; Wang, Yanli; Chen, Yulong; Lin, Yan; Zhu, Ninghong; Zheng, Huadong; Wu, Min; Cheng, Daxing; Li, Yandong; Bai, Liang; Fan, Jianglin; Liu, Enqi

2014-01-01

314

Cytokines and atherosclerosis: a comprehensive review of studies in mice  

PubMed Central

In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are monocyte-derived macrophages and T-lymphocytes. Both cell types produce a wide array of soluble inflammatory mediators (cytokines, chemokines) which are critically important in the initiation and perpetuation of the disease. This review summarizes the currently available information from mouse studies on the contribution of a specified group of cytokines expressed in atherosclerotic lesions, viz. interleukins (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, IL-20) and macrophage-associated cytokines [tumour necrosis factor-? (TNF-?); macrophage migration inhibitory factor (MIF); interferon-? (IFN-?); colony stimulating factors G-CSF,-M-CSF,-GM-CSF) to atherogenesis. Emphasis is put on the consistency of the effects of these cytokines, i.e. inasmuch an effect depends on the experimental approach applied (overexpression/deletion, strain, gender, dietary conditions, and disease stage). An important outcome of this survey is (i) that only for a few cytokines there is sufficient consistent data allowing classifying them as typically proatherogenic (IL-1, IL-12, IL-18, MIF, IFN-?, TNF-?, and M-CSF) or antiatherogenic (IL-10) and (ii) that some cytokines (IL-4, IL-6 and GM-CSF) can exert pro- or anti-atherogenic effects depending on the experimental conditions. This knowledge can be used for improved early detection, prevention and treatment of atherosclerosis. PMID:18487233

Kleemann, Robert; Zadelaar, Susanne; Kooistra, Teake

2008-01-01

315

Assessment of Coronary Atherosclerosis using Optical Coherence Tomography.  

PubMed

Optical coherence tomography (OCT) is a catheter-based imaging system that uses near-infrared light to produce cross-sectional images of the coronary arteries. With its extraordinarily high resolution (10-20 ?m), OCT allows clinicians to observe various morphological features of coronary atherosclerosis in vivo. For example, intimal thickening presents as homogeneous, signal-rich regions on OCT, while fibroatheroma with a lipid-rich necrotic core is characterized by the presence of signal-poor regions with a diffuse border. Furthermore, plaque rupture is detected in 50?70% of culprit lesions of acute coronary syndrome (ACS), and plaque erosion develops over areas of intimal thickening and/or thick-cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with hypertension and chronic renal disease. Platelet-rich thrombi are visualized as low backscattering structures and often detected in patients with unstable angina, whereas red blood cell-rich thrombi exhibit a high backscattering structure with signal-free shadowing and are frequently noted in patients with acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has been shown to be a predictor of subsequent plaque progression and acute coronary events, while vasa vasorum and the macrophage density are associated with a thin fibrous cap and large necrotic core as well as increased serum levels of inflammatory biomarkers. One current challenge of OCT examinations is to detect morphologic characteristics capable of discriminating vulnerable from stable plaques. The ability to detect vulnerable plaques in vivo would allow physicians to identify patients at high risk for adverse coronary events, thus significantly helping to prevent ACS. PMID:25069815

Kubo, Takashi; Tanaka, Atsushi; Ino, Yasushi; Kitabata, Hironori; Shiono, Yasutsugu; Akasaka, Takashi

2014-09-24

316

Unihemispheric Burst Suppression  

PubMed Central

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS. PMID:25309713

Villemarette-Pittman, Nicole R.; Rogers, Cornel T.; Torres-Delgado, Frank; Olejniczak, Piotr W.; England, John D.

2014-01-01

317

Neointima formation in a restenosis model is suppressed in midkine-deficient mice  

PubMed Central

Neointima formation is a common feature of atherosclerosis and restenosis after balloon angioplasty. To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation. MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery. Neointima formation in a restenosis model was strongly suppressed in MK-deficient mice. Continuous administration of MK protein to MK-deficient mice restored neointima formation. Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice. Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro. These results indicate that MK plays a critical role in neointima formation at least in part owing to its ability to mediate leukocyte recruitment. PMID:10683378

Horiba, Mitsuru; Kadomatsu, Kenji; Nakamura, Eishin; Muramatsu, Hisako; Ikematsu, Shinya; Sakuma, Sadatoshi; Hayashi, Kenji; Yuzawa, Yukio; Matsuo, Seiichi; Kuzuya, Masafumi; Kaname, Tadashi; Hirai, Makoto; Saito, Hidehiko; Muramatsu, Takashi

2000-01-01

318

Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.  

PubMed Central

Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet. The C57BL/6 strain differs from most inbred strains by having lower HDL concentrations and a high risk of developing early atherosclerotic lesions when fed an atherogenic diet. The relative HDL deficiency and atherosclerosis susceptibility of the C57BL/6 strain are corrected with the expression of a human apolipoprotein AI (apo AI) transgene in this genetic background. To examine if increases in apo AI and HDL are also effective in minimizing apo E deficiency--induced atherosclerosis, we introduced the human apo AI transgene into the hypercholesterolemic apo E knockout background. Similar elevations of total plasma cholesterol occurred in both the apo E knockout and apo E knockout mice also expressing the human apo AI transgene. The latter animals, however, also showed a two- to threefold increase in HDL and a sixfold decrease in susceptibility to atherosclerosis. This study demonstrates that elevating the concentration of apo AI reduces atherosclerosis in apo E deficient-mice and suggests that elevation of apo AI and HDL may prove to be a useful approach for treating unrelated causes of heightened atherosclerosis susceptibility. PMID:8040345

Pászty, C; Maeda, N; Verstuyft, J; Rubin, E M

1994-01-01

319

Male-Specific Association between a ?-Secretase Polymorphism and Premature Coronary Atherosclerosis  

PubMed Central

Background Atherosclerosis is a common multifactorial disease resulting from an interaction between susceptibility genes and environmental factors. The causative genes that contribute to atherosclerosis are elusive. Based on recent findings with a Wistar rat model, we speculated that the ?-secretase pathway may be associated with atherosclerosis. Methodology/Principal Findings We have tested for association of premature coronary atherosclerosis with a non-synonymous single-nucleotide polymorphism (SNP) in the ?-secretase component APH1B (Phe217Leu; rs1047552), a SNP previously linked to Alzheimer's disease. Analysis of a Dutch Caucasian cohort (780 cases; 1414 controls) showed a higher prevalence of the risk allele in the patients (odds ratio (OR)?=?1.35), albeit not statistically different from the control population. Intriguingly, after gender stratification, the difference was significant in males (OR?=?1.63; p?=?0.033), but not in females (OR?=?0.50; p?=?0.20). Since Phe217Leu-mutated APH1B showed reduced ?-secretase activity in mouse embryonic fibroblasts, the genetic variation is likely functional. Conclusion/Significance We conclude that, in a male-specific manner, disturbed ?-secretase signalling may play a role in the susceptibility for premature coronary atherosclerosis. PMID:18987747

van Loo, Karen M. J.; Dejaegere, Tim; van Zweeden, Martine; van Schijndel, Jessica E.; Wijmenga, Cisca; Trip, Mieke D.; Martens, Gerard J. M.

2008-01-01

320

Short telomeres protect from diet-induced atherosclerosis in apolipoprotein E-null mice.  

PubMed

By imposing a replicative defect in most somatic cells, gradual telomere attrition during aging is thought to progressively impair cellular function and viability and may contribute to age-related disease. Immune cells play important roles in all phases of atherosclerosis, a multifactorial disease that prevails within the elderly. Because shorter telomeres have been found in circulating blood leukocytes of human patients with advanced coronary atherosclerosis, it has been suggested that telomere shortening may predispose the organism to atheroma development. In this study, we assessed the impact of telomere attrition on atherogenesis induced by dietary cholesterol in apolipoprotein E (apoE)-deficient mice, a well-established model of experimental atherosclerosis that recapitulates important aspects of the human disease. Our study shows that late-generation mice doubly deficient in apoE and telomerase RNA experience telomere attrition and a substantial reduction of atherosclerosis compared with control mice with intact telomerase, in spite of sustained hypercholesterolemia in response to the atherogenic diet. Short telomeres impaired the proliferation of both lymphocytes and macrophages, an important step in atherosclerosis development. Therefore, telomere exhaustion resulting in replicative immunosenescence may serve as a mechanism for restricting atheroma progression. PMID:14688198

Poch, Enric; Carbonell, Paz; Franco, Sonia; Díez-Juan, Antonio; Blasco, María A; Andrés, Vicente

2004-02-01

321

Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis  

PubMed Central

CD40 ligand (CD40L), identified as a costimulatory molecule expressed on T cells, is also expressed and functional on platelets. We investigated the thrombotic and inflammatory contributions of platelet CD40L in atherosclerosis. Although CD40L-deficient (Cd40l?/?) platelets exhibited impaired platelet aggregation and thrombus stability, the effects of platelet CD40L on inflammatory processes in atherosclerosis were more remarkable. Repeated injections of activated Cd40l?/? platelets into Apoe?/? mice strongly decreased both platelet and leukocyte adhesion to the endothelium and decreased plasma CCL2 levels compared with wild-type platelets. Moreover, Cd40l?/? platelets failed to form proinflammatory platelet-leukocyte aggregates. Expression of CD40L on platelets was required for platelet-induced atherosclerosis as injection of Cd40l?/? platelets in contrast to Cd40l+/+ platelets did not promote lesion formation. Remarkably, injection of Cd40l+/+, but not Cd40l?/?, platelets transiently decreased the amount of regulatory T cells (Tregs) in blood and spleen. Depletion of Tregs in mice injected with activated Cd40l?/? platelets abrogated the athero-protective effect, indicating that CD40L on platelets mediates the reduction of Tregs leading to accelerated atherosclerosis. We conclude that platelet CD40L plays a pivotal role in atherosclerosis, not only by affecting platelet-platelet interactions but especially by activating leukocytes, thereby increasing platelet-leukocyte and leukocyte-endothelium interactions. PMID:20705757

Lievens, Dirk; Zernecke, Alma; Seijkens, Tom; Soehnlein, Oliver; Beckers, Linda; Munnix, Imke C. A.; Wijnands, Erwin; Goossens, Pieter; van Kruchten, Roger; Thevissen, Larissa; Boon, Louis; Flavell, Richard A.; Noelle, Randolph J.; Gerdes, Norbert; Biessen, Erik A.; Daemen, Mat J. A. P.; Heemskerk, Johan W. M.; Weber, Christian

2010-01-01

322

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis  

PubMed Central

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000?UI of ?-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

Busso, Dolores; Mascareno, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolas; Quiroz, Alonso; Amigo, Ludwig; Valdes, Gloria; Rigotti, Attilio

2014-01-01

323

Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis.  

PubMed

Recent studies indicate that periodontal disease is associated with the development of early atherosclerotic lesions in the carotid artery. Since inflammation is a key feature in both atherosclerosis and periodontal disease, a common mediator of the two diseases could be anticipated. Leukotrienes are lipid-derived inflammatory mediators recently implicated in the pathogenesis of atherosclerosis and previously shown to be produced in periodontitis. The aim of the present study was to detect leukotrienes in gingival crevicular fluid (GCF) from subjects with atherosclerosis. Carotid ultrasonography and oral clinical examination were performed in 19 periodontitis patients and 16 healthy subjects. Atherosclerotic plaques were detected on ultrasound examination in 13 subjects with periodontis, and in 5 of the healthy subjects. Elevated concentrations of leukotriene B(4) and cysteinyl-leukotrienes were detected in GCF from subjects with a high dental plaque index (PLI>0.3), supporting an increased leukotriene formation in periodontitis. In addition, subjects with atherosclerotic plaques had significantly elevated concentrations of cysteinyl-leukotrienes in their GCF as compared with subjects without a visible plaque. Finally, the increased cysteinyl-leukotriene concentrations in GCF from atherosclerotic subjects were observed also when sub groups of periodontis patients and healthy subjects were compared separately. In summary, increased GCF concentrations of cysteinyl-leukotrienes were correlated to measures of both periodontitis and atherosclerosis. These results suggest that increased leukotriene formation may represent a possible link between periodontitis and atherosclerosis and a risk factor marker for both diseases. PMID:16930607

Bäck, Magnus; Airila-Månsson, Stella; Jogestrand, Tomas; Söder, Birgitta; Söder, Per-Osten

2007-08-01

324

Mitral and aortic valve sclerosis/calcification and carotid atherosclerosis: results from 1065 patients.  

PubMed

This study assesses whether aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are associated with carotid artery atherosclerosis, independently of traditional cardiovascular risk factors. A total of 1065 patients underwent both echocardiography and carotid artery ultrasound scanning. AVS and MAC were defined as focal areas of increased echogenicity and thickening of the aortic leaflets or mitral valve annulus. Carotid artery atherosclerosis was defined as presence/absence of any atherosclerotic plaque or presence/absence of plaque >50 %. Of 1065 patients (65 ± 9 years; 38 % female) who comprised the study population, 642 (60 %) had at least one atherosclerotic plaque. AVS, but not mitral valve sclerosis; was associated with the presence of carotid atherosclerosis (odds ratio (OR) 1.9, 95 % confidence interval (CI) 1.2-3.9; P = 0.005) and the degree of carotid atherosclerosis (OR 2.1, 95 % CI 1.2-3.9; P = 0.01) in a multivariate model including age, gender, previous ischemic heart disease, hypertension, dyslipidemia, smoking, diabetes, family cardiovascular history, left ventricular size, mass, and ejection fraction, and left atrial size. AVS is a significant predictor of carotid atherosclerosis, independently of other cardiovascular clinical and echocardiographic risk factors. PMID:24196525

Rossi, Andrea; Faggiano, Pompilio; Amado, Alexandra E; Cicoira, Mariantonietta; Bonapace, Stefano; Franceschini, Lorenzo; Dini, Frank L; Ghio, Stefano; Agricola, Eustachio; Temporelli, Pier Luigi; Vassanelli, Corrado

2014-11-01

325

Using multimodal femtosecond CARS imaging to determine plaque burden in luminal atherosclerosis  

NASA Astrophysics Data System (ADS)

Luminal atherosclerosis imaging was demonstrated by multimodal femtosecond CARS microscopy (MM-CARS). Using a myocardial infarction-prone rabbit model of atherosclerosis, this study demonstrated the utility of multimodal CARS imaging in determining atherosclerotic plaque burden through two types of image analysis procedures. Firstly, multimodal CARS images were evaluated using a signal-intensity parameter based on intensity changes derived from the multi-channel data (e.g. TPEF, SHG and CARS) to classify plaque burden within the vessel. Secondly, the SHG images that mainly correspond to collagen fibrils were evaluated using a texture analysis model based on the first-order statistical (FOS) parameters of the image histogram. Correlation between FOS parameters of collagen images with atherosclerosis plaque burden was established. A preliminary study of using spectroscopic CARS in identifying the different lipid components within the plaque was also discussed.

Ko, Alex C.-T.; Mostaço-Guidolin, Leila B.; Ridsdale, Andrew; Pegoraro, Adrian F.; Smith, Michael S. D.; Slepkov, Aaron; Hewko, Mark D.; Kohlenberg, Elicia K.; Schattka, Bernie; Stolow, Albert; Sowa, Michael G.

2011-03-01

326

Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis  

PubMed Central

Atherosclerosis underlies the major causes of death in the Western World. Our main goal is to detect early changes of atherosclerosis and to identify subjects at highest cardiovascular risk that may aid in the development of prevention approaches and better management that will decrease cardiovascular morbidity and mortality. The new methods that are of interest include the advanced vascular ultrasound methods, the infra red and near infra red imaging techniques, the EndoPat device that reflects peripheral arterial tone, the electron beam computed tomography, the magnetic resonance imaging, and the molecular imaging techniques. In this review we will focus on the future of advanced imaging techniques that are being developed to detect early (pre-clinical) development of atherosclerosis. PMID:23888178

Blum, Arnon; Nahir, Menachem

2013-01-01

327

Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice  

PubMed Central

Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

2012-01-01

328

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease  

PubMed Central

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

Otani, Hajime

2013-01-01

329

Subclinical atherosclerosis: what it is, what it means and what we can do about it  

PubMed Central

Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase. Disease progression can lead eventually to the occurrence of acute cardiovascular events such as myocardial infarction, unstable angina pectoris and sudden cardiac death. While the disease is still in a subclinical stage, however, the presence of atherosclerosis can be identified by several methods, including coronary angiography, intravascular ultrasonography, B-mode ultrasonography, computed tomography and magnetic resonance imaging. Based on the results of imaging studies, statin therapy can slow, halt or even reverse the progression of atherosclerotic disease, depending on the intensity of treatment. Whether to screen and treat patients for subclinical atherosclerosis remains controversial. Although atheromatous plaque burden reduction has not yet been definitively correlated with significant decreases in risk for acute coronary events in asymptomatic patients, statin therapy contributes significantly to the risk reduction observed in clinical trials in patients with and without overt coronary disease. PMID:18564201

Toth, P P

2008-01-01

330

Screening for subclinical atherosclerosis by noninvasive methods in asymptomatic patients with risk factors  

PubMed Central

Atherosclerosis is a leading cause of cardiovascular death due to the increasing prevalence of the disease and the impact of risk factors such as diabetes, obesity or smoking. Sudden cardiac death is the primary consequence of coronary artery disease in 50% of men and 64% of women. Currently the only available strategy to reduce mortality in the at-risk population is primary prevention; the target population must receive screening for atherosclerosis. The value of screening for subclinical atherosclerosis is still relevant, it has become standard clinical practice with the emergence of new noninvasive techniques (radio frequency [RF] measurement of intima-media thickness [RFQIMT] and arterial stiffness [RFQAS], and flow-mediated vasodilatation [FMV]), which have been used by our team since 2007 and are based on detection marker integrators which reflect the deleterious effect of risk factors on arterial remodeling before the onset of clinical events. These techniques allow the study of values according to age and diagnosis of the pathological value, the thickness of the intima media (RFQIMT), the speed of the pulse wave (RFQAS), and the degree of endothelial dysfunction (FMV). This screening is justified in asymptomatic patients with cardiovascular risk factors (hypertension, diabetes, obesity, dyslipidemia, and tobacco smoking). Studies conducted by RF coupled with two-dimensional echo since 2007 have led to a more detailed analysis of the state of the arterial wall. The various examinations allow an assessment of the degree of subclinical atherosclerosis and its impact on arterial remodeling and endothelial function. The use of noninvasive imaging in screening and early detection of subclinical atherosclerosis is reliable and reproducible and allows us to assess the susceptibility of our patients with risk factors and ensures better monitoring of atherosclerosis, thus reducing the occurrence of cardiovascular events in the long term. PMID:23761967

Castellon, Xavier; Bogdanova, Vera

2013-01-01

331

Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.  

PubMed Central

We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations made in this study, we suggest that the antisperm antibodies that form after vasectomy may result in circulating immune complexes that exacerbate atherosclerosis. Images PMID:6765957

Clarkson, T B; Alexander, N J

1980-01-01

332

Genetic-Genomic Replication to Identify Candidate Mouse Atherosclerosis Modifier Genes  

PubMed Central

Objective Genetics plays a large role in atherosclerosis susceptibility in humans and mice. We attempted to confirm previously determined mouse atherosclerosis?associated loci and use bioinformatics and transcriptomics to create a catalog of candidate atherosclerosis modifier genes at these loci. Methods and Results A strain intercross was performed between AKR and DBA/2 mice on the apoE?/? background generating 166 F2 progeny. Using the phenotype log10 of the aortic root lesion area, we identified 3 suggestive atherosclerosis quantitative trait loci (Ath QTLs). When combined with our prior strain intercross, we confirmed 3 significant Ath QTLs on chromosomes 2, 15, and 17, with combined logarithm of odds scores of 5.9, 5.3, and 5.6, respectively, which each met the genome?wide 5% false discovery rate threshold. We identified all of the protein coding differences between these 2 mouse strains within the Ath QTL intervals. Microarray gene expression profiling was performed on macrophages and endothelial cells from this intercross to identify expression QTLs (eQTLs), the loci that are associated with variation in the expression levels of specific transcripts. Cross tissue eQTLs and macrophage eQTLs that replicated from a prior strain intercross were identified. These bioinformatic and eQTL analyses produced a comprehensive list of candidate genes that may be responsible for the Ath QTLs. Conclusions Replication studies for clinical traits as well as gene expression traits are worthwhile in identifying true versus false genetic associations. We have replicated 3 loci on mouse chromosomes 2, 15, and 17 that are associated with atherosclerosis. We have also identified protein coding differences and multiple replicated eQTLs, which may be useful in the identification of atherosclerosis modifier genes. PMID:23525445

Hsu, Jeffrey; Smith, Jonathan D.

2013-01-01

333

11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis  

PubMed Central

11?-Hydroxysteroid dehydrogenase type-1 (11?-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11?-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11?-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective 11?-HSD1 inhibitor or crossed with 11?-HSD1-KO mice to generate double knockouts (DKOs) and challenged with an atherogenic Western diet. 11?-HSD1 inhibition or deficiency attenuated atherosclerosis (74–76%) without deleterious effects on plaque structure. This occurred without affecting plasma lipids or glucose, suggesting independence from classical metabolic risk factors. KO plaques were not more inflamed and indeed had 36% less T-cell infiltration, associated with 38% reduced circulating monocyte chemoattractant protein-1 (MCP-1) and 36% lower lesional vascular cell adhesion molecule-1 (VCAM-1). Bone marrow (BM) cells are key to the atheroprotection, since transplantation of DKO BM to irradiated ApoE-KO mice reduced atherosclerosis by 51%. 11?-HSD1-null macrophages show 76% enhanced cholesterol ester export. Thus, 11?-HSD1 deficiency reduces atherosclerosis without exaggerated lesional inflammation independent of metabolic risk factors. Selective 11?-HSD1 inhibitors promise novel antiatherosclerosis effects over and above their benefits for metabolic risk factors via effects on BM cells, plausibly macrophages.—Kipari, T., Hadoke, P. W. F., Iqbal, J., Man, T. Y., Miller, E., Coutinho, A. E., Zhang, Z., Sullivan, K. M., Mitic, T., Livingstone, D. E. W., Schrecker, C., Samuel, K., White, C. I., Bouhlel, M. A., Chinetti-Gbaguidi, G., Staels, B., Andrew, R., Walker, B. R., Savill, J. S., Chapman, K. E., Seckl, J. R. 11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis. PMID:23303209

Kipari, Tiina; Hadoke, Patrick W. F.; Iqbal, Javaid; Man, Tak-Yung; Miller, Eileen; Coutinho, Agnes E.; Zhang, Zhenguang; Sullivan, Katie M.; Mitic, Tijana; Livingstone, Dawn E. W.; Schrecker, Christopher; Samuel, Kay; White, Christopher I.; Bouhlel, M. Amine; Chinetti-Gbaguidi, Giulia; Staels, Bart; Andrew, Ruth; Walker, Brian R.; Savill, John S.; Chapman, Karen E.; Seckl, Jonathan R.

2013-01-01

334

Progression of coronary atherosclerosis in African-American patients  

PubMed Central

Background African-Americans with coronary artery disease (CAD) demonstrate worse clinical outcomes than Caucasians. While this is partly due to a lack of accessibility to established therapies, the mechanisms underlying this difference remain to be elucidated. We aimed to characterize the progression of coronary atherosclerosis in African-Americans with CAD. Methods 3,479 patients with CAD underwent serial intravascular ultrasound (IVUS) imaging to evaluate atheroma progression in 7 clinical trials of anti-atherosclerotic therapies. Risk factor control and atheroma progression were compared between African-Americans (n=170) and Caucasians (n=3,309). Results African-Americans were more likely to be female (51.8% vs. 28.1%, P<0.001), have a higher body mass index (32.8±6.0 vs. 31.3±5.8 kg/m2, P=0.002) and greater history of hypertension (85.9% vs. 78.8%, P=0.02), diabetes (41.8% vs. 30.6%, P=0.002) and stroke (12.9% vs. 3.0%, P<0.001). Despite a high use of anti-atherosclerotic medications (93% statin, 89% aspirin, 79% ?-blocker, 52% ACE inhibitor), African-Americans demonstrated higher levels of LDL-C (2.4±0.7 vs. 2.2±0.7 mmol/L, P=0.006), CRP (2.9 vs. 2.0 mg/dL, P<0.001) and systolic blood pressure (133±15 vs. 129±13 mmHg, P<0.001) at follow-up. There was no significant difference in atheroma volume at baseline (189.0±82.2 vs. 191.6±83.3 mm3, P=0.82) between two groups. Serial evaluation demonstrated a greater increase in atheroma volume in African-Americans (0.51±2.1 vs. –3.1±1.7 mm3, P=0.01). This difference persisted with propensity matching accounting for differences in risk factor control (0.1±2.1 vs. –3.7±1.7 mm3, P=0.02). Conclusions African-Americans with CAD achieve less optimal risk factor control and greater atheroma progression. These findings support the need for more intensive risk factor modification in African-Americans. PMID:24282765

Kataoka, Yu; Hsu, Amy; Wolski, Kathy; Uno, Kiyoko; Puri, Rishi; Tuzcu, E. Murat; Nissen, Steven E.

2013-01-01

335

Functional Inhibition of Ras by S-trans, trans-Farnesyl Thiosalicylic Acid Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice  

Microsoft Academic Search

Background—Atherosclerosis is a multifactorial disorder involving inflammatory processes. These responses are associated with robust activation of signaling cascades by diverse cell surface receptors in a variety of cell types. The processes that are involved in atherosclerosis would likely require intact Ras pathways, which play a key role in the control of cell growth, differentiation, and apoptosis. Methods and Results—We examined

Jacob George; Arnon Afek; Pnina Keren; Itzhak Herz; Iris Goldberg; Roni Haklai; Yoel Kloog; Gad Keren

336

PPAR activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH  

E-print Network

actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation) in the apoE2-KI mouse. Objectives : 1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and 2) to study whether PPAR

Boyer, Edmond

337

The effect of novocain hydrolysis products on the course and reverse development of atherosclerosis under experimental conditions  

Microsoft Academic Search

The work is devoted to the study of the effect produced by products of novocain hydrolysis (as compared to its whole molecule) on the course and resolution of experimental atherosclerosis in rabbits. Two series of experiments were staged: the first one investigated the effect, of para-aminobenzoic acid (PABA) and diethylaminoethanol (DAE) on the course of experimental atherosclerosis; the second one

A. F. Ryzhova; T. A. Mel

1964-01-01

338

Modulation of paraoxonases during infectious diseases and its potential impact on atherosclerosis  

PubMed Central

The paraoxonase (PON) gene family includes three members, PON1, PON2 and PON3, aligned in tandem on chromosome 7 in humans and on chromosome 6 in mice. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. The major goal of this review is to highlight the modulation of each of the PONs by infective (bacterial, viral and parasitic) agents, which may shed a light on the interaction between infectious diseases and PONs activities in order to effectively reduce the risk of developing atherosclerosis. PMID:22824324

2012-01-01

339

Long Term Follow Up of Celiac Disease--Is Atherosclerosis a Problem?  

PubMed Central

Celiac disease (CD) is a lifelong condition and it often involves impaired nutrition, wide spectrum of symptoms and it requires constant dietetic treatment. The impact of the gluten-free diet on patients’ nutritional status and on the other biochemical parameters is being widely investigated. In this article we looked into particular risk factors that might lead to increased prevalence of atherosclerosis in CD patients, including nutritional status, gluten-free diet, lipids profile and concomitant disease—type 1 diabetes mellitus. Here, we present the current data and research on these risk factors of atherosclerosis with respect to celiac disease. PMID:25050927

Rybak, Anna; Cukrowska, Bozena; Socha, Jerzy; Socha, Piotr

2014-01-01

340

Effect of apolipoprotein E polymorphism on serum lipid, lipoproteins, and atherosclerosis in hemodialysis patients.  

PubMed

Atherosclerosis and cardiovascular disease are the main causes of death in hemodialysis patients. Possession of the apolipoprotein E4 (ApoE4) allele has been associated with increased levels of serum lipids and with coronary and carotid artery atherosclerosis. We investigated the possible relationship between ApoE polymorphism and atherosclerosis risk factors in hemodialysis patients. Two hundred sixty-nine hemodialysis patients (115 women, 154 men) were included in our study. The mean patient age and mean hemodialysis duration were 45.8 +/- 15.3 years and 52.6 +/- 40.6 months, respectively. Testing was done on all patients to determine ApoE genotype and serum levels of total cholesterol (T-Cho), low-density lipoprotein (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG), lipoprotein (a) (Lp[a]), intact parathormone (iPTH), and fibrinogen. ApoE genotype was identified with the polymerase chain reaction. Ultrasonographic measurement of carotid artery intima media thickness (IMT) was used to diagnose atherosclerosis. We also analyzed ApoE polymorphism and risk factors such as age, gender, duration of hemodialysis, smoking, and hypertension in relation to the presence of atherosclerosis. Serum T-Cho and LDL-C levels were higher in patients with the ApoE4/3 phenotype than in those with ApoE3/3 and ApoE3/2 phenotypes (P < 0.05). However, there was no statistically significant link between ApoE polymorphism and serum levels of TG, HDL-C, or Lp(a) (P > 0.05). Apart from a relationship with age and duration of hemodialysis (P < 0.05), we found no significant association between atherosclerosis and ApoE polymorphism or the other risk factors analyzed (P > 0.05). In conclusion, although ApoE polymorphism significantly affects serum levels of T-Cho and LDL-C in hemodialysis patients, this study indicates that ApoE polymorphism is not associated with the presence of atherosclerosis in these individuals. The high incidence of atherosclerosis in these patients underlines the need for further research on other possible causative factors. PMID:11007687

Güz, G; Nurhan Ozdemir, F; Sezer, S; I?iklar, I; Arat, Z; Turan, M; Haberal, M

2000-10-01

341

Infections, Immunity, and Atherosclerosis Associations of Antibodies to Chlamydia pneumoniae, Helicobacter pylori, and Cytomegalovirus With Immune Reactions to Heat-Shock Protein 60 and Carotid or Femoral Atherosclerosis  

Microsoft Academic Search

Background—Atherogenesis involves inflammatory processes in which infections are incriminated as possible contributors. Methods and Results—We evaluated cardiovascular risk factors as well as seropositivity to Chlamydia pneumoniae , Helicobacter pylori, and cytomegalovirus in a population-based study. A significant association between prevalence and severity of atherosclerosis in carotid and femoral arteries and IgA antibodies to C pneumoniae was demonstrated that was not

Manuel Mayr; Stefan Kiechl; Johann Willeit; Georg Wick; Qingbo Xu

342

Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis  

PubMed Central

Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100?g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100?g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470?ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192?nm. In addition, they showed that supplementation of zinc (350?ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280?nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

2013-01-01

343

Paradoxical effects of thought suppression  

Microsoft Academic Search

In a first experiment, subjects verbalizing the stream of consciousness for a 5-min period were asked to try not to think of a white bear, but to ring a bell in case they did. As indicated both by mentions and by bell rings, they were unable to suppress the thought as instructed. On being asked after this suppression task to

Daniel M. Wegner; David J. Schneider; Samuel R. Carter III; Teri L. White

1987-01-01

344

Ginger Extract Consumption Reduces Plasma Cholesterol, Inhibits LDL Oxidation and Attenuates Development of Atherosclerosis in Atherosclerotic, Apolipoprotein E-Deficient Mice  

Microsoft Academic Search

Oxidative modification of LDL is thought to play a key role in the pathogenesis of atherosclerosis. Consumption of nutrients rich in phenolic antioxidants has been shown to be associated with attenuation of development of atherosclerosis. This study was undertaken to investigate the ex vivo effect of standardized ginger extract on the development of atherosclerosis in apolipoprotein E-deficient (E0) mice, in

Bianca Fuhrman; Mira Rosenblat; Tony Hayek; Raymond Coleman; Michael Aviram

345

Postictal generalized EEG suppression  

PubMed Central

Objective: To determine the consistency and facilitating cofactors of postictal generalized EEG suppression (PGES) of >20 seconds after convulsive seizures (CS), a suggested predictor of sudden unexpected death in epilepsy risk. Methods: We retrospectively reviewed video-EEG data of people with ?2 recorded CS. Presence and duration of PGES were assessed by 2 independent observers blinded to patient status. Intraindividual consistency of PGES >20 seconds was determined and correlations with clinical characteristics were analyzed after correction for individual effects and the varying number of seizures. Results: One hundred fifty-four seizures in 59 people were analyzed. PGES >20 seconds was found in 37 individuals (63%) and 57 (37%) of CS. The proportion of persons in whom PGES occurred consistently (presence or absence of PGES >20 seconds in all CS) was lower in those with more CS. PGES of >20 seconds was more frequent in seizures arising from sleep (odds ratio 3.29, 95% confidence interval 1.21–8.96) and when antiepileptic medication was tapered (odds ratio 4.80, 95% confidence interval 1.27–18.14). Conclusion: Apparent PGES consistency was less frequent in people with more CS recorded, suggesting that PGES is an inconsistent finding in any one individual. Thus, we believe that PGES >20 seconds is not a reliable predictor of sudden unexpected death in epilepsy. Sleep and antiepileptic drug reduction appear to facilitate the occurrence of PGES. PMID:23966251

Lamberts, Robert J.; Gaitatzis, Athanasios; Sander, Josemir W.; Elger, Christian E.

2013-01-01

346

Group Differences in Suppression Skill*  

PubMed Central

It is proposed that there are group differences in suppression skill, and one such grouping is the distinction between more versus less skilled university-aged comprehenders. Experiments supporting this proposal and demonstrating that university-aged adults differ in their ability to suppress irrelevant, inappropriate, potentially interfering information are reviewed. Many of these experiments have been replicated with other groups, which also hypothetically differ in their ability to suppress inappropriate information. Two new sets of experiments are reviewed. In one, the prediction that less skilled comprehenders- because they are less skilled at suppression- should be better at comprehending puns is evaluated. In the other, the prediction that less skilled comprehenders- because they are less skilled at suppression- are better able to shift to a different meaning of a homonym is evaluated. Both sets of data are evaluated with respect to a general slowing explanation and scaling artifacts.

Gernsbacher, Morton Ann

2014-01-01

347

What effect does controlling platelets have on atherosclerosis?  

PubMed

Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets. PMID:7695180

Numano, F; Kishi, Y; Ashikaga, T; Hata, A; Makita, T; Watanabe, R

1995-01-17

348

Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis  

PubMed Central

Rationale Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-?-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation. Objective To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis. Methods and Results Apolipoprotein-E (Apoe)?/? mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-? in diseased arteries. Apoe?/? mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-? expression. Conclusions Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses. PMID:24425713

Knight, Jason S.; Luo, Wei; O'Dell, Alexander A.; Yalavarthi, Srilakshmi; Zhao, Wenpu; Subramanian, Venkataraman; Guo, Chiao; Grenn, Robert C.; Thompson, Paul R.; Eitzman, Daniel T.; Kaplan, Mariana J.

2014-01-01

349

Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation  

PubMed Central

Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis-related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis. PMID:25318463

LIN, MIN; ZHAO, LIN; ZHAO, WENLONG; WENG, JING

2014-01-01

350

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction?  

PubMed Central

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

351

Effects of atorvastatin in combination with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia.  

PubMed

The aim of this study was to observe the effects of atorvastatin combined with ezetimibe on carotid atherosclerosis in elderly patients with hypercholesterolemia. A total of 84 elderly hypercholesterolemic patients complicated with carotid atherosclerosis were divided into control group (atorvastatin alone) and combined group (atorvastatin combined with ezetimibe) and treated for 12 months. Carotid atherosclerosis-related indicators including blood lipid and high-sensitivity C-reactive protein (hsCRP) were determined before and after treatment. The levels of carotid intima-media thickness (CIMT), serum low density lipoprotein cholesterol (LDL-C) and hsCRP were markedly decreased (P < 0.05) after treatment in the two groups, while the reduction of the levels of CIMT, serum LDL-C and hsCRP was more significant in the combined group (P < 0.01). After treatment, the levels of CIMT, serum LDL-C and hsCRP were distinctly different between combined and control group (P < 0.05). The combination of atorvastatin with ezetimibe could further decrease LDL-C and hsCRP levels and have certain effects on the progression of carotid atherosclerosis in elderly patients with hypercholesterolemia. PMID:24737506

Luo, P; Li, L; Wang, L X; Zhu, H H; Du, S; Wu, S L; Han, Y G; Wang, G G

2014-01-01

352

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans  

E-print Network

of a low carotid artery IMT. Atherosclerotic arterial disease is the leading cause of mor- bidity improve a number of risk factors for atherosclerosis, including blood pressure (BP), serum total and lipoproteins, fasting plasma glucose and insulin, blood pres- sure (BP), high-sensitivity C-reactive protein

Lakes, Roderic

353

Are immigrant enclaves healthy places to live? The Multiethnic Study of Atherosclerosis  

Microsoft Academic Search

The growing size and changing composition of the foreign-born population in the USA highlights the importance of examining the health consequences of living in neighborhoods with higher proportions of immigrants. Using data from the Multi-ethnic Study of Atherosclerosis in four US cities, we examined whether neighborhood immigrant composition was associated with health behaviors (diet, physical activity) among Hispanic and Chinese

Theresa L. Osypuk; Ana V. Diez Roux; Craig Hadley; Namratha R. Kandula

2009-01-01

354

Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway  

PubMed Central

Atherosclerosis is currently considered an inflammatory disease. Much attention has been focused on the potential role of inflammatory mediators as prognostic/diagnostic markers or therapeutic targets of atherosclerotic cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and functionally unique chemokine with a well documented role in atherosclerosis. In its membrane bound form it promotes the firm adhesion of rolling leucocytes onto the vessel wall, while in its soluble form it serves as a potent chemoattractant for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque. Studies on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway ameliorates the severity of atherosclerosis, while genetic epidemiology has confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is associated with a reduced risk of atherosclerotic disease in humans. Although several studies support an important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization, this does not necessarily suggest that this pathway is a suitable therapeutic target or that CX3CL1 can serve as a prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine pathway are clearly warranted to justify the clinical relevance of its role in atherosclerosis. PMID:23974513

Apostolakis, Stavros; Spandidos, Demetrios

2013-01-01

355

Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice  

PubMed Central

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-? were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

2012-01-01

356

Human C-reactive protein does not promote atherosclerosis in transgenic rabbits  

PubMed Central

Background Although there is a statistically significant association between modestly raised baseline plasma C-reactive protein (CRP) values and future cardiovascular events, the debate is still unsettled as to whether CRP plays a causal role in the pathogenesis of atherosclerosis. Methods and Results We generated two lines of transgenic (Tg) rabbits expressing human CRP (hCRP). The plasma levels of hCRP in hCRP-Tg-1 and hCRP-Tg-2 rabbits were 0.4 ± 0.13 (n=14) and 57.8 ± 20.6 mg/L (n=12), respectively. Also, hCRP isolated from Tg rabbit plasma exhibited the ability to activate the rabbit complement. To define the role of hCRP in atherosclerosis, we compared the susceptibility of hCRP-Tg rabbits to cholesterol-rich diet-induced aortic and coronary atherosclerosis with that of non-Tg rabbits. After being fed with a cholesterol-rich diet for 16 weeks, Tg and non-Tg rabbits developed similar hypercholesterolemia and lesion sizes in both aortic and coronary arteries. Immunohistochemical staining and Western blotting revealed that hCRP was indeed present in the lesions but did not affect macrophage accumulation and smooth muscle cell proliferation of the lesions. Conclusions Neither high nor low plasma concentrations of human CRP affected aortic or coronary atherosclerosis lesion formation in hCRP-Tg rabbits. PMID:19901190

Koike, Tomonari; Kitajima, Shuji; Yu, Ying; Nishijima, Kazutoshi; Zhang, Jifeng; Ozaki, Yukio; Morimoto, Masatoshi; Watanabe, Teruo; Bhakdi, Sucharit; Asada, Yujiro; Chen, Y. Eugene; Fan, Jianglin

2010-01-01

357

Human apolipoprotein A-II protects against diet-induced atherosclerosis in transgenic rabbits  

PubMed Central

Objective Apolipoprotein A-II (apo A-II) is the second major apolipoprotein of HDLs, yet its pathophysiological roles in the development of atherosclerosis remain unknown. We aimed to examine whether apo A-II plays any role in atherogenesis and if so, to elucidate the mechanism involved. Methods and Results We compared the susceptibility of human apo A-II transgenic (Tg) rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermate rabbits. Tg rabbits developed significantly less aortic and coronary atherosclerosis than their non-Tg littermates while total plasma cholesterol levels were similar. Atherosclerotic lesions of Tg rabbits were characterized by reduced macrophages and smooth muscle cells and apo A-II immunoreactive proteins were frequently detected in the lesions. Tg rabbits exhibited low levels of plasma CRP and blood leukocytes compared to non-Tg rabbits and HDLs of Tg rabbit plasma exerted stronger cholesterol efflux activity and inhibitory effects on the inflammatory cytokine expression by macrophages in vitro than HDLs isolated from non-Tg rabbits. In addition, ?-VLDLs of Tg rabbits were less sensitive to copper-induced oxidation than ?-VLDLs of non-Tg rabbits. Conclusions These results suggest that enrichment of apo A-II in HDL particles has atheroprotective effects and apo A-II may become a target for the treatment of atherosclerosis. PMID:23241412

Wang, Yao; Niimi, Manabu; Nishijima, Kazutoshi; Waqar, Ahmed Bilal; Yu, Ying; Koike, Tomonari; Kitajima, Shuji; Liu, Enqi; Inoue, Tomohiro; Kohashi, Masayuki; Keyamura, Yuka; Yoshikawa, Tomohiro; Zhang, Jifeng; Ma, Loretta; Zha, Xiaohui; Watanabe, Teruo; Asada, Yujiro; Chen, Y. Eugene; Fan, Jianglin

2013-01-01

358

Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in ApoE?/? mice  

PubMed Central

Objective Exposure to dioxins has been shown to contribute to the development of inflammatory diseases such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)-dependent activation of inflammatory mediators and the formation of cholesterol laden foam cells. However, the mechanisms responsible for the formation of atherosclerotic lesions mediated through AhR have not been identified. Methods and Results An in vitro macrophage and an ApoE?/? mouse model were used to determine whether chemokines and their receptors are responsible for the AhR-mediated atherogenesis. Exposure of ApoE?/? mice to TCDD caused a time-dependent progression of atherosclerosis, which was associated with induction of inflammatory genes including Interleukin (IL)-8 as well as F4/80 and matrix metalloproteinase (MMP)-12. High fat diet enhanced the TCDD-mediated inflammatory response and deteriorated the formation of complex atheromas. Treatment with a CXCR2 inhibitor and an AhR antagonist reduced the TCDD-induced progression of early atherosclerotic lesions in ApoE?/? mice. Conclusions The results suggest that CXCR2 mediates the atherogenic activity of environmental pollutants, such as dioxins, and contributes to the development of atherosclerosis through the induction of a vascular inflammatory response by activating the AhR-signaling pathway. PMID:21441140

Wu, Dalei; Nishimura, Noriko; Kuo, Victoria; Fiehn, Oliver; Shahbaz, Sevini; Winkle, Laura Van; Matsumura, Fumio; Vogel, Christoph

2011-01-01

359

Resveratrol : natural properties against atherosclerosis, associated pro-inflammatory effects and aging  

E-print Network

- 1 - Resveratrol : natural properties against atherosclerosis, associated pro- inflammatory of resveratrol Whom all correspondence: Pr. Norbert Latruffe GDR-CNRS2583, IFR 92, Laboratory of Molecular 62 50 or 03 80 39 62 50 E-mail : latruffe@u-bourgogne.fr Abbreviations : Keywords : Resveratrol

Paris-Sud XI, Université de

360

Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis.  

PubMed Central

Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis. Images PMID:8022789

Tsai, J C; Perrella, M A; Yoshizumi, M; Hsieh, C M; Haber, E; Schlegel, R; Lee, M E

1994-01-01

361

Effects of heterozygous lipoprotein lipase deficiency on diet-induced atherosclerosis in mice  

Microsoft Academic Search

Heterozygous lipoprotein lipase deficiency (LPL 1 \\/ 2 ) is common and has been implicated in prema- ture atherosclerosis in epidemiologic studies. However, in vitro data suggest that LPL deficiency in the vascular wall may be antiatherogenic. To address the role of LPL in ath- erosclerosis, LPL 1 \\/ 2 mice in the C57BL\\/6J background were fed an atherogenic diet

Clay F. Semenkovich; Trey Coleman; Alan Daugherty

362

Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr?/? mice[S  

PubMed Central

Obesity-associated chronic inflammation contributes to metabolic dysfunction and propagates atherosclerosis. Recent evidence suggests that increased dietary cholesterol exacerbates inflammation in adipose tissue and liver, contributing to the proatherogenic milieu. The ability of the citrus flavonoid naringenin to prevent these cholesterol-induced perturbations is unknown. To assess the ability of naringenin to prevent the amplified inflammatory response and atherosclerosis induced by dietary cholesterol, male Ldlr?/? mice were fed either a cholesterol-enriched high-fat or low-fat diet supplemented with 3% naringenin for 12 weeks. Naringenin, through induction of hepatic fatty acid (FA) oxidation and attenuation of FA synthesis, prevented hepatic steatosis, hepatic VLDL overproduction, and hyperlipidemia induced by both cholesterol-rich diets. Naringenin attenuated hepatic macrophage infiltration and inflammation stimulated by dietary cholesterol. Insulin resistance, adipose tissue expansion, and inflammation were alleviated by naringenin. Naringenin attenuated the cholesterol-induced formation of both foam cells and expression of inflammatory markers in peritoneal macrophages. Naringenin significantly decreased atherosclerosis and inhibited the formation of complex lesions, which was associated with normalized aortic lipids and a reversal of aortic inflammation. We demonstrate that in mice fed cholesterol-enriched diets, naringenin attenuates peripheral and systemic inflammation, leading to protection from atherosclerosis. These studies offer a therapeutically relevant alternative for the prevention of cholesterol-induced metabolic dysregulation. PMID:23269394

Assini, Julia M.; Mulvihill, Erin E.; Sutherland, Brian G.; Telford, Dawn E.; Sawyez, Cynthia G.; Felder, Sarah L.; Chhoker, Sanjiv; Edwards, Jane Y.; Gros, Robert; Huff, Murray W.

2013-01-01

363

The Quantification of Vitamin D Receptors in Coronary Arteries and Their Association with Atherosclerosis  

PubMed Central

Objective The activated vitamin D receptor (VDR) may have an important role in vascular health. The objective of this study was to determine whether there is an association between the expression of VDRs in coronary arteries and the extent of diet-induced atherosclerosis. Methods Utilizing a cohort of 39 postmenopausal female cynomolgus monkeys with varying stages of atherosclerosis, histologic sections of the left anterior descending artery (LAD) were analyzed for plaque cross-sectional area, plaque thickness, and VDR quantity using immunohistochemical H-score analysis. The quantities of VDRs were analyzed as a continuous variable and were divided at the median intimal H-score into high vs. low groupings. Results In the LAD, a significant negative correlation was observed between the quantity of VDR and plaque size (both cross-sectional area [p<0.001] and plaque thickness [p<0.001]). Monkeys in the low VDR group had a significantly greater cross-sectional plaque area (1.2 mm2) and greater plaque thickness (0.3 mm) than those in the high VDR group (0.4 mm2, p=0.005; 0.1 mm, p=0.003, respectively). Conclusions Lower concentrations of VDRs in a main coronary artery were associated with greater atherosclerotic plaque size in postmenopausal female monkeys. Given that coronary artery atherosclerosis is a major cause of coronary heart disease in postmenopausal women, further research to ascertain the relationship between VDRs and atherosclerosis is warranted. PMID:22542390

Schnatz, Peter F.; Nudy, Matthew; O'Sullivan, David M.; Jiang, Xuezhi; Cline, J. Mark; Kaplan, Jay R.; Clarkson, Thomas B.; Appt, Susan E.

2012-01-01

364

A VLP-based vaccine against interleukin-1? protects mice from atherosclerosis.  

PubMed

Interleukin (IL)-1? is a potent proinflammatory cytokine that has been implicated in the development of atherosclerosis. We investigated whether a vaccine inducing IL-1? neutralizing antibodies could interfere with disease progression in a murine model of atherosclerosis. We immunized Apolipoprothin E (ApoE)-deficient mice with a vaccine (IL-1?-C-Q?) consisting of full-length, native IL-1? chemically conjugated to virus-like particles derived from the bacteriophage Q?. ApoE(-/-) mice were administered six injections of IL-1?-C-Q? or nonconjugated Q? over a period of 160 days while being maintained on a western diet. Atherosclerosis was measured in the descending aorta and in cross-sections at the aortic root. Macrophage infiltration in the aorta was measured using CD68. Expression levels of VCAM-1, ICAM-1, and MCP-1 were quantified by RT-PCR. Immunization against IL-1? reduced plaque progression in the descending aorta by 50% and at the aortic root by 37%. Macrophage infiltration in the aorta was reduced by 22%. Inflammation was also reduced in the adventitia, with a decrease of 54% in peri-aortic infiltrate score and reduced expression levels of VCAM-1 and ICAM-1. Active immunization targeting IL-1? reduced both the inflammatory reaction in the plaque as well as plaque progression. In summary, vaccination against IL-1? protected ApoE(-/-) mice against disease, suggesting that this may be a potential treatment option for atherosclerosis. PMID:23254454

Tissot, Alain C; Spohn, Gunther; Jennings, Gary T; Shamshiev, Abdijapar; Kurrer, Michael O; Windak, Renata; Meier, Marco; Viesti, Miriam; Hersberger, Martin; Kündig, Thomas M; Ricci, Romeo; Bachmann, Martin F

2013-03-01

365

Atherosclerosis and hypertension induction by lead and cadmium ions: an effect prevented by calcium ion  

SciTech Connect

In epidemiological studies, both positive and negative correlations have been found between cardiovascular disease and mortality and the presence of several inorganic ions in the drinking water. In an attempt to resolve this apparent disagreement, we exposed White Carneau pigeons to drinking water containing calcium (100 ppm), magnesium (30 ppm), lead (0.8 ppm), or cadmium (0.6 ppm) and used a 2/sup 4/-factorial design to measure the effects of these elements in atherosclerosis and hypertension. The results indicate that (i) lead and cadmium induced aortic atherosclerosis and hypertension, and (ii) calcium protects against the cardiovascular effects of cadmium. Furthermore, the effects were indications that magnesium antagonized the atherosclerotic protective effect of calcium. We suggest that, if these results with the pigeon can be applied to humans, the incidence of aortic atherosclerosis and hypertension should be significantly higher in areas where the drinking water contains magnesium, lead, and cadmium with a relatively low calcium concentration. Furthermore, if hard and soft water produce similar levels of lead and cadmium uptakes, the level of magnesium may be an additional factor in aortic atherosclerosis.

Revis, N.W. (Oak Ridge National Lab., TN); Zinsmeistery, A.R.; Bull, R.

1981-10-01

366

Elevated heart rate and atherosclerosis: An overview of the pathogenetic mechanisms  

Microsoft Academic Search

Several epidemiological studies have reported that an elevated heart rate is associated with coronary atherosclerosis independently of other risk factors. In this review we explore the pathophysiologic mechanisms involved in the pro-atherosclerotic effect of elevated heart rate, apart from its association with sympathetic tone. An elevated heart rate enhances the magnitude and frequency of the tensile stress imposed on the

George D. Giannoglou; Yiannis S. Chatzizisis; Chrysanthos Zamboulis; George E. Parcharidis; Dimitri P. Mikhailidis; George E. Louridas

2008-01-01

367

Diagonal ear lobe crease and atherosclerosis: A review of the medical literature and dental implications  

PubMed Central

In Spain a significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. The diagonal ear lobe crease (DELC) has been characterized in the medical literature as a surrogate marker which can identify high risk patients having occult atherosclerosis. This topic however has not been examined in either the medical or dental literature emanating from Spain. The majority of clinical, angiography and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. A minority of studies have however failed to support this hypothesis. More recently reports using B mode ultrasound have also linked DELC to atherosclerosis of the carotid artery and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. DELC is readily visible during head and neck cancer screening examinations. In conjunction with the patient’s medical history, vital signs, and panoramic radiograph, the DELC may assist in atherosclerotic risk assessment. Key words: Diagonal ear lobe crease, atherosclerosis disease, calcified carotid artery, atheromas, panoramic radiographs. PMID:21743392

Lopez-Lopez, Jose; Velasco-Ortega, Eugenio

2012-01-01

368

Atherosclerosis 161 (2002) 4554 Anti-atherogenic effects of the acyl-CoA:cholesterol acyltransferase  

E-print Network

Atherosclerosis 161 (2002) 45­54 Anti-atherogenic effects of the acyl-CoA:cholesterol; accepted 5 June 2001 Abstract Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown of the ACAT inhibitor, avasimibe (CI-1011), during foam cell formation and during cholesterol efflux from

Terasaki, Mark

369

Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries characterized by leukocyte accumulation in the vessel wall. Both innate and adaptive immune responses contribute to atherogenesis, but the identity of atherosclerosis-relevant antigens and the role of antigen presentation in this disease remain poorly characterized. We developed live-cell imaging of explanted aortas to compare the behavior and role of APCs in normal and atherosclerotic mice. We found that CD4+ T cells were capable of interacting with fluorescently labeled (CD11c-YFP+) APCs in the aortic wall in the presence, but not the absence, of cognate antigen. In atherosclerosis-prone Apoe–/–CD11c-YFP+ mice, APCs extensively interacted with CD4+ T cells in the aorta, leading to cell activation and proliferation as well as secretion of IFN-? and TNF-?. These cytokines enhanced uptake of oxidized and minimally modified LDL by macrophages. We conclude that antigen presentation by APCs to CD4+ T cells in the arterial wall causes local T cell activation and production of proinflammatory cytokines, which promote atherosclerosis by maintaining chronic inflammation and inducing foam cell formation. PMID:22886300

Koltsova, Ekaterina K.; Garcia, Zacarias; Chodaczek, Grzegorz; Landau, Michael; McArdle, Sara; Scott, Spencer R.; von Vietinghoff, Sibylle; Galkina, Elena; Miller, Yury I.; Acton, Scott T.; Ley, Klaus

2012-01-01

370

The pathology of atherosclerosis: plaque development and plaque responses to medical treatment.  

PubMed

Atherosclerosis develops over the course of 50 years, beginning in the early teenage years. The causes of this process appear to be lipid retention, oxidation, and modification, which provoke chronic inflammation at susceptible sites in the walls of all major conduit arteries. Initial fatty streaks evolve into fibrous plaques, some of which develop into forms that are vulnerable to rupture, causing thrombosis or stenosis. Erosion of the surfaces of some plaques and rupture of a plaque's calcific nodule into the artery lumen also may trigger thrombosis. The process of plaque development is the same regardless of race/ethnicity, sex, or geographic location, apparently worldwide. However, the rate of development is faster in patients with risk factors such as hypertension, tobacco smoking, diabetes mellitus, obesity, and genetic predisposition. Clinical trial data demonstrate that treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) favorably alters plaque size, cellular composition, chemical composition, and biological activities centered on inflammation and cholesterol metabolism, as well as the risk of clinical events due to atherosclerosis. Even with advanced atherosclerosis, statins begin to improve clinical risk within 4 months. During long-term follow-up in clinical trials for up to 11 years with or without further treatment, clinical benefit remains significant, indicating the durability of treatment-induced changes in the development of plaque. Thus, atherosclerosis, a disease heretofore viewed as inevitably progressive, can be treated to significantly alter arterial lesions and reduce their clinical consequences. PMID:19110086

Insull, William

2009-01-01

371

Does high plant feed magnesium and potassium protect healthy ruminants from atherosclerosis? A review  

Microsoft Academic Search

The literature data were surveyed to clarify the role of magnesium and potassium in the development of atherosclerosis (AS) in cows and the findings were compared with human data. Special attention was paid to the eastern Finland where AS is very common in humans and absent in the cattle. A hypothesis is proposed that high magnesium and potassium intakes at

Seppo Haaranen

2003-01-01

372

Large Artery Calcification on Dialysis Patients Is Located in the Intima and Related to Atherosclerosis  

PubMed Central

Summary Background and objectives Vascular calcification (VC) has a significant effect in cardiovascular diseases on dialysis patients. However, VC is assessed with x-ray-based techniques, which do not inform about calcium localization (intima, media, atherosclerosis-related). The aim of this work is to study VC and its related factors using arterial ultrasound to report the exact location of calcium. Design, setting, participants, & measurements This was an observational, cross-sectional, case-control study that included 232 patients in dialysis and 208 age- and sex-matched controls with normal kidney function. Demographic data and laboratory values were collated. Carotid, femoral, and brachial ultrasounds were performed to assess VC and atherosclerosis burden using a standardized protocol. Results Cardiovascular risk factors were predominantly found in controls, although the burden of atherosclerosis was higher in the dialysis group. VC was significantly more prevalent in the group of patients on dialysis than control subjects, and in both groups the most prevalent pattern of VC was linear calcification located in the intima of the artery wall. Age and undergoing dialysis (with or without previous cardiovascular diseases) were positively and significantly associated with linear calcification. Conversely, the absence of atherosclerosis and low levels of C-reactive protein and phosphorus significantly impeded the development of linear calcification. Conclusions VC in large, conduit arteries is more prevalent in patients on dialysis than controls and is predominantly located in a linear fashion in the intima of the arteries. PMID:20930091

Coll, Blai; Betriu, Angels; Martinez-Alonso, Montserrat; Amoedo, Maria Luisa; Arcidiacono, Maria Vittoria; Borras, Merce; Valdivielso, Jose Manuel

2011-01-01

373

Can atherosclerosis be one of the causes of anterior spinal artery thrombosis?  

PubMed

A middle aged diabetic, hypertensive, dyslipidemic, heavy alcohol consumer man came with sudden onset upper back pain and quadriparesis. Examination showed upper motor type quadriparesis with sensation of pain loss up to level of C7 and totally spared proprioception. MRI spine showed features suggestive of anterior spinal artery stroke. Can atherosclerosis be a causative factor for spinal stroke? PMID:24397082

Malik, Yasir Mehmood; Dar, Javeed Ahmed

2012-01-01

374

Noncollagenous Bone Matrix Proteins, Calcification, and Thrombosis in Carotid Artery Atherosclerosis  

Microsoft Academic Search

Advanced atherosclerosis is often associated with dystrophic calcification, which may contribute to plaque rupture and thrombosis. In this work, the localization and association of the noncollagenous bone matrix proteins osteonectin, osteopontin, and osteocalcin with calcification, lipoproteins, thrombus\\/hemorrhage (T\\/H), and matrix metalloproteinases (MMPs) in human carotid arteries from endarterectomy samples have been determined. According to the recent American Heart Association classification,

Alessandra Bini; Kenneth G. Mann; Bohdan J. Kudryk; Frederick J. Schoen

2010-01-01

375

A nuclear microscopy study of trace elements Ca, Fe, Zn and Cu in atherosclerosis  

Microsoft Academic Search

Quantitative mapping of trace elements Ca, Fe, Zn and Cu can be achieved in biological tissue using a nuclear microprobe. Presented here is a brief review of the work we have carried out in the last decade using the nuclear microscope to try and elucidate the role of trace elements Fe, Zn, Cu and Ca in induced atherosclerosis in New

F. Watt; R. Rajendran; M. Q. Ren; B. K. H. Tan; B. Halliwell

2006-01-01

376

The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?  

Microsoft Academic Search

There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this \\

M. Vergeer; A. G. Holleboom; J. J. P. Kastelein; J. A. Kuivenhoven

2010-01-01

377

Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development.  

PubMed

As olive oil is the main source of calories in the Mediterranean diet, a great deal of research has been devoted to characterizing its role in atherosclerosis. Virgin olive oil is an oily matrix that contains hydrocarbons, mainly squalene; triterpenes such as uvaol, erythrodiol, oleanolic, and maslinic acid; phytosterols; and a wide range of phenolic compounds comprising simple phenols, flavonoids, secoiridoids, and lignans. In this review, we analyze the studies dealing with atherosclerosis and olive oil in several species. A protective role of virgin olive oil against atherosclerosis has been shown in ApoE-deficient mice and hamsters. In the former animal, sex, dose, and dietary cholesterol are modulators of the outcome. Contradictory findings have been reported for rabbits, a circumstance that could be due to the profusion of experimental designs, differing in terms of doses and animal strains, as well as sources of olive oils. This role has yet to be fully validated in humans. Minor components of olive oil have been shown to be involved in atherosclerosis protection. Nevertheless, evidence of the potential of isolated compounds or the right combination of them to achieve the antiatherosclerotic effect of virgin olive oil is inconclusive and will undoubtedly require further experimental support. PMID:22760979

Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

2012-07-01

378

Genetic determinants of atherosclerosis, obesity, and energy balance in consomic mice.  

PubMed

Metabolic diseases such as obesity and atherosclerosis result from complex interactions between environmental factors and genetic variants. A panel of chromosome substitution strains (CSSs) was developed to characterize genetic and dietary factors contributing to metabolic diseases and other biological traits and biomedical conditions. Our goal here was to identify quantitative trait loci (QTLs) contributing to obesity, energy expenditure, and atherosclerosis. Parental strains C57BL/6 and A/J together with a panel of 21 CSSs derived from these progenitors were subjected to chronic feeding of rodent chow and atherosclerotic (females) or diabetogenic (males) test diets, and evaluated for a variety of metabolic phenotypes including several traits unique to this report, namely fat pad weights, energy balance, and atherosclerosis. A total of 297 QTLs across 35 traits were discovered, two of which provided significant protection from atherosclerosis, and several dozen QTLs modulated body weight, body composition, and circulating lipid levels in females and males. While several QTLs confirmed previous reports, most QTLs were novel. Finally, we applied the CSS quantitative genetic approach to energy balance, and identified three novel QTLs controlling energy expenditure and one QTL modulating food intake. Overall, we identified many new QTLs and phenotyped several novel traits in this mouse model of diet-induced metabolic diseases. PMID:25001233

Spiezio, Sabrina H; Amon, Lynn M; McMillen, Timothy S; Vick, Cynthia M; Houston, Barbara A; Caldwell, Mark; Ogimoto, Kayoko; Morton, Gregory J; Kirk, Elizabeth A; Schwartz, Michael W; Nadeau, Joseph H; LeBoeuf, Renée C

2014-12-01

379

Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model  

PubMed Central

Inflammation and oxidative stress play fundamental roles in the pathogenesis of atherosclerosis. Myeloperoxidase has been extensively implicated as a key mediator of inflammatory and redox-dependent processes in atherosclerosis. However, the effect of synthetic myeloperoxidase inhibitors on atherosclerosis has been insufficiently studied. In this study, ApoE?/? mice were randomized to low- and high-dose INV-315 groups for 16 weeks on high-fat diet. INV-315 resulted in reduced plaque burden and improved endothelial function in response to acetylcholine. These effects occurred without adverse events or changes in body weight or blood pressure. INV-315 treatment resulted in a decrease in iNOS gene expression, superoxide production and nitrotyrosine content in the aorta. Circulating IL-6 and inflammatory CD11b+/Ly6Glow/7/4hi monocytes were significantly decreased in response to INV-315 treatment. Acute pretreatment with INV-315 blocked TNF?-mediated leukocyte adhesion in cremasteric venules and inhibited myeloperoxidase activity. Cholesterol efflux was significantly increased by high-dose INV-315 via ex-vivo reverse cholesterol transport assays. Our results suggest that myeloperoxidase inhibition may exert anti-atherosclerotic effects via inhibition of oxidative stress and enhancement of cholesterol efflux. These findings demonstrate a role for pharmacologic modulation of myeloperoxidase in atherosclerosis. PMID:23251382

Liu, Cuiqing; Desikan, Rajagopal; Ying, Zhekang; Gushchina, Liubov; Kampfrath, Thomas; Deiuliis, Jeffrey; Wang, Aixia; Xu, Xiaohua; Zhong, Jixin; Rao, Xiaoquan; Sun, Qinghua; Maiseyeu, Andrei; Parthasarathy, Sampath; Rajagopalan, Sanjay

2012-01-01

380

Animal, In Vitro, and Ex Vivo Models of Flow-Dependent Atherosclerosis: Role of Oxidative Stress  

PubMed Central

Abstract Atherosclerosis is an inflammatory disease preferentially occurring in curved or branched arterial regions, whereas straight parts of the arteries are protected, suggesting a close relationship between flow and atherosclerosis. However, evidence directly linking disturbed flow to atherogenesis is just emerging, thanks to the recent development of suitable animal models. In this article, we review the status of various animal, in vitro, and ex vivo models that have been used to study flow-dependent vascular biology and atherosclerosis. For animal models, naturally flow-disturbed regions such as branched or curved arterial regions as well as surgically created models, including arterio-venous fistulas, vascular grafts, perivascular cuffs, and complete, incomplete, or partial ligation of arteries, are used. Although in vivo models provide the environment needed to mimic the complex pathophysiological processes, in vitro models provide simple conditions that allow the study of isolated factors. Typical in vitro models use cultured endothelial cells exposed to various flow conditions, using devices such as cone-and-plate and parallel-plate chambers. Ex vivo models using isolated vessels have been used to bridge the gap between complex in vivo models and simple in vitro systems. Here, we review these flow models in the context of the role of oxidative stress in flow-dependent inflammation, a critical proatherogenic step, and atherosclerosis. Antioxid. Redox Signal. 15, 1433–1448. PMID:20712399

Rezvan, Amir; Ni, Chih-Wen; Alberts-Grill, Noah

2011-01-01

381

Involvement of Chlamydia pneumoniae in Atherosclerosis: More Evidence for Lack of Evidence  

Microsoft Academic Search

During the past 15 years, many studies have been devoted to the relationship of Chlamydia pneumoniae and atherosclerosis: the serologic link has been investigated, and chlamydial organ- isms have been detected in lesions by electron microscopy, immunohistochemistry, in vitro cultivation, PCR, or in situ hybridization; efforts have been made to produce atheroscle- rosis experimentally in animals by inoculation of C.

Margareta M. Ieven; Vicky Y. Hoymans

2005-01-01

382

The role of the infectious agents in the pathogenesis and evolution of atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory process due to the endothelial reaction to stress risk factors, only some of which are known. Clinical and experimental observations have suggested that several infectious agents are involved in this process. These agents, particularly the germ Chlamydia pneumoniae, and their relationship to the atheromata are described. Two hypotheses concerning how these infectious agents act are

Claudio Blasi

2004-01-01

383

Atherosclerotic Biomarkers and Aortic Atherosclerosis by Cardiovascular Magnetic Resonance Imaging in the Framingham Heart Study  

PubMed Central

Background The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community?based cohort. Methods and Results We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high?sensitivity C?reactive protein, fibrinogen, intercellular adhesion molecule?1, interleukin?6, interleukin?18, lipoprotein?associated phospholipase?A2 activity and mass, monocyte chemoattractant protein?1, P?selectin, and tumor necrosis factor receptor?2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age? and sex?adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). Conclusions In our community?based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors. PMID:24242683

Hong, Susie N.; Gona, Philimon; Fontes, Joao D.; Oyama, Noriko; Chan, Raymond H.; Kenchaiah, Satish; Tsao, Connie W.; Yeon, Susan B.; Schnabel, Renate B.; Keaney, John F.; O'Donnell, Christopher J.; Benjamin, Emelia J.; Manning, Warren J.

2013-01-01

384

The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia.  

PubMed

As patients with autoimmune rheumatic diseases live longer due to improved therapies and preventive measures, death and disability from atherosclerosis, particularly myocardial infarcts, are increasing. The relative risks for atherosclerosis vary from approximately 1.6 in ankylosing spondylitis and psoriatic arthritis to 3.0 in rheumatoid arthritis (RA), and 6.0 in systemic lupus erythematosus (SLE). Increased risks are found when analyzed by atherosclerotic events, causes of death, or surrogate measures of atherosclerosis, such as carotid artery plaque, intimal-media thickness, or coronary artery calcification. At all ages among adults, atherosclerosis is increased in patients with SLE or RA compared to healthy controls. For example, in women with SLE under the age of 40 years, approximately 13% have carotid plaque compared to 2% of controls; over age 59 the percentages are 71 and 45, respectively. For patients with RA, prevalence is 7% under the age of 40 in patients compared to zero in controls; over 59 years the prevalences are 80% and 44%, respectively. In this review we will discuss the mechanisms involved as well as an overview of the natural history in pathobiology. PMID:17433865

Hahn, Bevra H; Grossman, Jennifer; Chen, Weiling; McMahon, Maureen

2007-01-01

385

Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments  

NASA Astrophysics Data System (ADS)

Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

386

Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation.  

PubMed

Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis?related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis. PMID:25318463

Lin, Min; Zhao, Lin; Zhao, Wenlong; Weng, Jing

2014-12-01

387

[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].  

PubMed

Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been investigated. As regards the biological mechanisms of chronic stress, the hypothalamic-pituitary-adrenal axis and the sympathetic system have been investigated. The studies have mainly been carried out on primates, and, to a less extent, on other mammals such as rabbit and wolf and on some species of birds. In the animals under social isolation, subordination or hostility/anger, a significantly more severe atherosclerosis was present, besides an increased activity of the hypothalamic-pituitary-adrenal axis and sympathetic system. In conclusion, the results offered by animal models seem to satisfy the first of Kuller's criteria, as for the three above-mentioned psychosocial factors. PMID:17216916

Alboni, Paolo; Alboni, Marco

2006-11-01

388

Ursolic Acid Protects Diabetic Mice Against Monocyte Dysfunction and Accelerated Atherosclerosis  

PubMed Central

Aims Accelerated atherosclerosis is a major diabetic complication initiated by the enhanced recruitment of monocytes into the vasculature. In this study, we examined the therapeutic potential of the phytonutrients ursolic acid (UA) and resveratrol (RES) in preventing monocyte recruitment and accelerated atherosclerosis. Methods and Results Dietary supplementation with either RES or UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin in high-fat diet-fed LDL receptor-deficient mice. However, mice that received dietary UA for 11 weeks were significantly better protected and showed a 53% reduction in lesion formation while mice fed a RES-supplemented diet showed only a 31% reduction in lesion size. Importantly, UA was also significantly more effective in preventing the appearance of proinflammatory GR-1high monocytes induced by these diabetic conditions and reducing monocyte recruitment into MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively-stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment of THP-1 monocytes with RES or UA (0.3 – 10 ?M) for 15 h resulted in the dose-dependent inhibition of H2O2-accelerated chemotaxis in response to MCP-1, but with an IC50 of 0.4 ?M, UA was 2.7-fold more potent than RES. Conclusion Dietary UA is a potent inhibitor of monocyte dysfunction and accelerated atherosclerosis induced by diabetes. These studies identify ursolic acid as a potential therapeutic agent for the treatment of diabetic complications, including accelerated atherosclerosis, and provide a novel mechanism for the anti-atherogenic properties of ursolic acid. PMID:21752377

Ullevig, Sarah L.; Zhao, Qingwei; Zamora, Debora; Asmis, Reto

2011-01-01

389

Detection of Subclinical Atherosclerosis in Asymptomatic Subjects Using Ultrasound Radiofrequency-Tracking Technology  

PubMed Central

Objective Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis. Methods A total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT (MAXIMT), RF Quality IMT (RFQIMT), distensibility coefficient (), compliance coefficient (), index, index and local pulse wave velocity (). The subjects were categorized in four groups in terms of the number of risk factors: ‘zero’, ‘single’, ‘double’, and ‘multiple’, and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups. Results The subjects (n?=?145) with MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman’s rho correlation analysis of the whole group and the NA-subjects both showed that MAXIMT correlated positively with RFQIMT, , , and , and negatively with and (p<0.01). The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the ‘zero’, ‘single’, ‘double’, and ‘multiple’ groups. Conclusions The carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160 subjects, and these anatomical and mechanical parameters may potentially be used together with the IMT criteria to support subclinical atherosclerosis diagnosis. PMID:25369320

Meng, Long; Xiao, Yang; Wong, Kelvin K. L.; Abbott, Derek; Zheng, Hairong; Zheng, Rongqin; Qian, Ming

2014-01-01

390

Association of Carotid Artery Atherosclerosis with Circulating Biomarkers of Extracellular Matrix Remodeling: The Framingham Offspring Study  

PubMed Central

Objective To relate circulating biomarkers of extracellular matrix (ECM) turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound. Background Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate ECM remodeling, a key feature of atherosclerosis, and their circulating concentrations can be assayed. MMP-9, TIMP-1 and protocollagen-III n-terminal propeptide (PIIINP) may relate differentially to the severity of atherosclerosis at different carotid artery sites. However, data examining this premise are sparse. Design/Methods We related circulating MMP-9, TIMP-1 and/or PIIINP concentrations to carotid atherosclerosis on duplex ultrasound in1006 Framingham Offspring (mean age 58 years, 56% women) who attended a routine examination from 1995–1998. We used multivariable regression to relate MMP-9 (detectable versus undetectable), and TIMP-1 and PIIINP (age- and sex-specific quartiles) to internal carotid artery stenosis (>25%), and log-transformed common and internal carotid intima-media thickness (CC-IMT, IC-IMT, respectively). Results Detectable MMP-9 was associated with carotid stenosis (OR 1.71, p=0.032) but not with IMT. Higher TIMP-1 was associated with carotid stenosis (OR for Q4 versus Q1-3, 1.63, p=0.022) and a higher IC-IMT (? 0.057 ±0.025, Q4 versus Q1-3, p=0.023). Higher PIIINP (Q4 versus Q1-3) showed a borderline association with carotid stenosis (OR 1.45 for Q4 versus Q1-3, p=0.095) but not with IMT. TIMP-1 was not associated with CC-IMT. Conclusions In our community-based sample of middle-aged to older adults, higher circulating biomarkers of matrix remodeling were associated with a greater prevalence of carotid stenosis, and subclinical atherosclerosis in the IC artery. Our findings are consistent with regional differences in matrix remodeling in the carotid artery. PMID:18984437

Romero, Jose R.; Vasan, Ramachandran S.; Beiser, Alexa S.; Polak, Joseph F.; Benjamin, Emelia J.; Wolf, Philip A.; Seshadri, Sudha

2008-01-01

391

The role of iron metabolism as a mediator of macrophage inflammation and lipid handling in atherosclerosis  

PubMed Central

Iron is an essential mineral needed for normal physiologic processes. While its function in oxygen transport and other important physiologic processes is well known, less is understood about its role in inflammatory diseases such as atherosclerosis. Existing paradigms suggest iron as a driver of atherosclerosis through its actions as a pro-oxidant capable of causing lipid oxidation and tissue damage. Recently we and others have identified hemoglobin (Hb) derived iron as an important factor in determining macrophage differentiation and function in areas of intraplaque hemorrhage within human atherosclerosis. Hb associated macrophages, M(Hb), are distinct from traditional macrophage foam cells because they do not contain large amounts of lipid or inflammatory cytokines, are characterized by high levels of expression of mannose receptor (CD206) and CD163 in addition to producing anti-inflammatory cytokines such as IL-10. Despite the well-known role of iron as an catalyst capable of producing lipid peroxidation through generation of reactive oxygen species (ROS) such as hydroxyl radical, we and others have shown that macrophages in areas of intraplaque hemorrhage demonstrate reduced intracellular iron and ROS which triggers production of anti-inflammatory cytokines as well as genes involved in cholesterol e?ux. These data suggest that manipulation of macrophage iron itself may be a promising pharmacologic target for atherosclerosis prevention through its effects on macrophage inflammation and lipid metabolism. In this review we will summarize the current understanding of iron as it relates to plaque inflammation and discuss how further exploration of this subject may lead to new therapies for atherosclerosis. PMID:25221512

Habib, Anwer; Finn, Aloke V.

2014-01-01

392

Translational Mini-Review Series on Immunology of Vascular Disease: Accelerated atherosclerosis in vasculitis  

PubMed Central

Premature atherosclerosis has been observed during the course of different systemic inflammatory diseases such as rheumatoid arthritis and sytemic lupus erythematosus. Remarkably, relatively few studies have been published on the occurrence of accelerated atherosclerosis in patients with vasculitis. In giant cell arteritis (GCA), mortality because of ischaemic heart disease is not increased. In addition, intima media thickness (IMT) is lower in patients with GCA than in age-matched controls. In contrast, IMT is increased significantly in Takayasu arteritis, another form of large vessel vasculitis occurring in younger patients. In Takayasu arteritis and in Kawasaki disease, a form of medium-sized vessel vasculitis, accelerated atherosclerosis has been well documented. In small vessel vasculitis because of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis, cardiovascular diseases are a major cause of mortality. IMT measurements reveal conflicting results. During active disease these patients experience acceleration of the atherosclerotic process. However, when inflammation is controlled, these patients have atherosclerotic development as in healthy subjects. Several risk factors, such as diabetes and hypertension, are present more often in patients with vasculitis compared with healthy controls. In addition, steroids may be pro-atherogenic. Most importantly, many patients have impaired renal function, persistent proteinuria and increased levels of C-reactive protein, well-known risk factors for acceleration of atherosclerosis. Enhanced oxidation processes, persistently activated T cells and reduced numbers of regulatory T cells are among the many pathophysiological factors that play a role during acceleration of atherogenesis. Finally, autoantibodies that may be relevant for acceleration of atherosclerosis are found frequently in elevated titres in patients with vasculitis. Because patients have an increased risk for cardiovascular events, vasculitis should be treated with as much care as possible. In addition, treatment should be considered with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor-1 blockers, statins and acetylsalicyl acid. Finally, classical risk factors for cardiovascular disease should be monitored and treated as much as possible. PMID:19309350

Tervaert, J W Cohen

2009-01-01

393