Phosphate binding reduces aortic angiotensin-converting enzyme and enhances nitric oxide bioactivity in experimental renal insufficiency.

PubMed

Eräranta, Arttu; Törmänen, Suvi; Kööbi, Peeter; Vehmas, Tuija I; Lakkisto, Päivi; Tikkanen, Ilkka; Moilanen, Eeva; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka

2014-01-01

Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking. Fifteen weeks after 5/6 nephrectomy (NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham). Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups. Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.

Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling

PubMed Central

Förstermann, Ulrich; Li, Huige

2011-01-01

Nitric oxide (NO) produced by the endothelium is an important protective molecule in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS). Similar to all NOS isoforms, functional eNOS transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L-arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking reduce bioactive NO. These risk factors lead to an enhanced production of reactive oxygen species (ROS) in the vessel wall. NADPH oxidases represent major sources of this ROS and have been found upregulated in the presence of cardiovascular risk factors. NADPH-oxidase-derived superoxide avidly reacts with eNOS-derived NO to form peroxynitrite (ONOO-). The essential NOS cofactor (6R-)5,6,7,8-tetrahydrobiopterin (BH4) is highly sensitive to oxidation by this ONOO-. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting NOS to a superoxide-producing enzyme. Among conventional drugs, compounds interfering with the renin-angiotensin-aldosterone system and statins can reduce vascular oxidative stress and increase bioactive NO. In recent years, we have identified a number of small molecules that have the potential to prevent eNOS uncoupling and, at the same time, enhance eNOS expression. These include the protein kinase C inhibitor midostaurin, the pentacyclic triterpenoids ursolic acid and betulinic acid, the eNOS enhancing compounds AVE9488 and AVE3085, and the polyphenolic phytoalexin trans-resveratrol. Such compounds enhance NO production from eNOS also under pathophysiological conditions and may thus have therapeutic potential. PMID:21198553

Type of supplemented simple sugar, not merely calorie intake, determines adverse effects on metabolism and aortic function in female rats

PubMed Central

Sangüesa, Gemma; Shaligram, Sonali; Akther, Farjana; Roglans, Núria; Laguna, Juan C.; Rahimian, Roshanak

2017-01-01

High consumption of simple sugars causes adverse cardiometabolic effects. We investigated the mechanisms underlying the metabolic and vascular effects of glucose or fructose intake and determined whether these effects are exclusively related to increased calorie consumption. Female Sprague-Dawley rats were supplemented with 20% wt/vol glucose or fructose for 2 mo, and plasma analytes and aortic response to vasodilator and vasoconstrictor agents were determined. Expression of molecules associated with lipid metabolism, insulin signaling, and vascular response were evaluated in hepatic and/or aortic tissues. Caloric intake was increased in both sugar-supplemented groups vs. control and in glucose- vs. fructose-supplemented rats. Hepatic lipogenesis was induced in both groups. Plasma triglycerides were increased only in the fructose group, together with decreased expression of carnitine palmitoyltransferase-1A and increased microsomal triglyceride transfer protein expression in the liver. Plasma adiponectin and peroxisome proliferator-activated receptor (PPAR)-α expression was increased only by glucose supplementation. Insulin signaling in liver and aorta was impaired in both sugar-supplemented groups, but the effect was more pronounced in the fructose group. Fructose supplementation attenuated aortic relaxation response to a nitric oxide (NO) donor, whereas glucose potentiated it. Phenylephrine-induced maximal contractions were reduced in the glucose group, which could be related to increased endothelial NO synthase (eNOS) phosphorylation and subsequent elevated basal NO in the glucose group. In conclusion, despite higher caloric intake in glucose-supplemented rats, fructose caused worse metabolic and vascular responses. This may be because of the elevated adiponectin level and the subsequent enhancement of PPARα and eNOS phosphorylation in glucose-supplemented rats. NEW & NOTEWORTHY This is the first study comparing the effects of glucose and fructose consumption

Lactobacillus Fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.

PubMed

Toral, Marta; Romero, Miguel; Rodríguez-Nogales, Alba; Jiménez, Rosario; Robles-Vera, Iñaki; Algieri, Francesca; Chueca-Porcuna, Natalia; Sánchez, Manuel; de la Visitación, Néstor; Olivares, Mónica; García, Federico; Pérez-Vizcaíno, Francisco; Gálvez, Julio; Duarte, Juan

2018-05-30

Our aim was to analyse whether the probiotic Lactobacillus fermentum CECT5716 (LC40) could prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. Tacrolimus increased systolic blood pressure (SBP) and impaired endothelium-dependent relaxation to acetylcholine and these effects were partially prevented by LC40. Endothelial dysfunction induced by tacrolimus was related to both increased NADPH oxidase (NOX2) and uncoupled eNOS driven-superoxide production and Rho-kinase mediated eNOS inhibition. LC40 treatment prevented all the aortic changes induced by tacrolimus. LC40 restored the imbalance between T-helper 17 (Th17)/ regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and spleen. Tacrolimus induced gut dysbiosis, i.e. it decreased microbial diversity, increased Firmicutes/Bacteroidetes ratio and decreased acetate- and butyrate-producing bacteria and these effects were prevented by LC40. Fecal microbiota transplantation from LC40 treated mice to control mice prevented the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus. LC40 treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 down-regulation and prevention of eNOS-uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Functional significance of differential eNOS translocation

PubMed Central

Sánchez, Fabiola A.; Savalia, Nirav B.; Durán, Ricardo G.; Lal, Brajesh K.; Boric, Mauricio P.; Durán, Walter N.

2006-01-01

Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation. PMID:16679407

Influence of coronary artery diameter on eNOS protein content

NASA Technical Reports Server (NTRS)

Laughlin, M. H.; Turk, J. R.; Schrage, W. G.; Woodman, C. R.; Price, E. M.

2003-01-01

The purpose of this study was to test the hypothesis that the content of endothelial nitric oxide synthase (eNOS) protein (eNOS protein/g total artery protein) increases with decreasing artery diameter in the coronary arterial tree. Content of eNOS protein was determined in porcine coronary arteries with immunoblot analysis. Arteries were isolated in six size categories from each heart: large arteries [301- to 2,500-microm internal diameter (ID)], small arteries (201- to 300-microm ID), resistance arteries (151- to 200-microm ID), large arterioles (101- to 150-microm ID), intermediate arterioles (51- to 100-microm ID), and small arterioles(<50-microm ID). To obtain sufficient protein for analysis from small- and intermediate-sized arterioles, five to seven arterioles 1-2 mm in length were pooled into one sample for each animal. Results establish that the number of smooth muscle cells per endothelial cell decreases from a number of 10 to 15 in large coronary arteries to 1 in the smallest arterioles. Immunohistochemistry revealed that eNOS is located only in endothelial cells in all sizes of coronary artery and in coronary capillaries. Contrary to our hypothesis, eNOS protein content did not increase with decreasing size of coronary artery. Indeed, the smallest coronary arterioles had less eNOS protein per gram of total protein than the large coronary arteries. These results indicate that eNOS protein content is greater in the endothelial cells of conduit arteries, resistance arteries, and large arterioles than in small coronary arterioles.

Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation.

PubMed

Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C; Sessa, William C

2015-08-18

Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. Copyright © 2015, American Association for the Advancement of Science.

Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

PubMed Central

Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C.; Sessa, William C.

2016-01-01

Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID:26286023

Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

PubMed

Musicki, Biljana; Liu, Tongyun; Strong, Travis D; Lagoda, Gwen A; Bivalacqua, Trinity J; Burnett, Arthur L

2010-05-01

Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. These results

Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

PubMed

Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

2018-05-09

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

Folic acid modulates eNOS activity via effects on posttranslational modifications and protein–protein interactions☆

PubMed Central

Taylor, Sarah Y.; Dixon, Hannah M.; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

2013-01-01

Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein–protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment. PMID:23796957

Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

PubMed Central

Musicki, Biljana; Liu, Tongyun; Strong, Travis D.; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Burnett, Arthur L.

2010-01-01

Introduction Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement

Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia.

PubMed

Hofmann, Alejandro; Gosemann, Jan-Hendrik; Takahashi, Toshiaki; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

2014-08-01

Caveolin-1 (Cav-1) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav-1 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low-output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav-1 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav-1 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav-1 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav-1 and eNOS. Pulmonary Cav-1 gene expression levels were significantly decreased, while eNOS gene expression was significantly increased in nitrofen-induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav-1 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls. The striking evidence of markedly decreased gene and protein expression of Cav-1 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav-1 deficiency may play an important role in the pathogenesis of PH in the nitrofen-induced CDH. © 2014 Wiley Periodicals, Inc.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

ET-1 Stimulates Superoxide Production by eNOS Following Exposure of Vascular Endothelial Cells to Endotoxin.

PubMed

Gopalakrishna, Deepak; Pennington, Samantha; Karaa, Amel; Clemens, Mark G

2016-07-01

It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1. Human umbilical vein endothelial cells (HUVEC) or human microvascular endothelial cells (HMEC) were subjected to a 6-h treatment with LPS (250 ng/mL) or LPS and sepiapterin (100 μM) followed by a 30-min treatment with 100 μM L-Iminoethyl Ornithine (L-NIO) an irreversible eNOS inhibitor and 30-min treatment with ET-1 (10 nM). Conversion of [H]L-arginine to [H]L-citrulline was used to measure eNOS activity. Superoxide dismutase (SOD) inhibitable reduction of Cytochrome-C, dihydro carboxy fluorescein (DCF), and Mitosox was used to estimate ROS. LT-SDS PAGE was used to assess the degree of monomerization of the eNOS homodimer. Stimulation of HUVECs with ET-1 significantly increased NO synthesis by 1.4-fold (P < 0.05). ET-1 stimulation of LPS-treated HUVECs failed to increase NO production. Western blot for eNOS protein showed no change in eNOS protein levels. LPS alone resulted in an insignificant increase in ROS production as measured by cytochrome C that was increased 4.6-fold by ET-1 stimulation (P < 0.05). L-NIO significantly decreased ET-1-induced ROS production (P < 0.05). Sepiapterin significantly decreased ROS production in both; unstimulated and ET-1-stimulated LPS-treated groups, but did not restore NO production. DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress

Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.

PubMed

Krishnan, Manickam; Janardhanan, Preethi; Roman, Linda; Reddick, Robert L; Natarajan, Mohan; van Haperen, Rien; Habib, Samy L; de Crom, Rini; Mohan, Sumathy

2015-10-01

The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities.

Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS

PubMed Central

Elms, Shawn; Chen, Feng; Wang, Yusi; Qian, Jin; Askari, Bardia; Yu, Yanfang; Pandey, Deepesh; Iddings, Jennifer; Caldwell, Ruth B.

2013-01-01

Reduced production of nitric oxide (NO) is one of the first indications of endothelial dysfunction and precedes overt cardiovascular disease. Increased expression of Arginase has been proposed as a mechanism to account for diminished NO production. Arginases consume l-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and l-arginine depletion is thought to competitively reduce eNOS-derived NO. However, this simple relationship is complicated by the paradox that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. One mechanism proposed to explain this is compartmentalization of intracellular l-arginine into distinct, poorly interchangeable pools. In the current study, we investigated this concept by targeting eNOS and Arginase to different intracellular locations within COS-7 cells and also BAEC. We found that supplemental l-arginine and l-citrulline dose-dependently increased NO production in a manner independent of the intracellular location of eNOS. Cytosolic arginase I and mitochondrial arginase II reduced eNOS activity equally regardless of where in the cell eNOS was expressed. Similarly, targeting arginase I to disparate regions of the cell did not differentially modify eNOS activity. Arginase-dependent suppression of eNOS activity was reversed by pharmacological inhibitors and absent in a catalytically inactive mutant. Arginase did not directly interact with eNOS, and the metabolic products of arginase or downstream enzymes did not contribute to eNOS inhibition. Cells expressing arginase had significantly lower levels of intracellular l-arginine and higher levels of ornithine. These results suggest that arginases inhibit eNOS activity by depletion of substrate and that the compartmentalization of l-arginine does not play a major role. PMID:23792682

The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo.

PubMed

Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Di Lorenzo, Annarita; Harrison, Kenneth D; Huang, Paul L; Sessa, William C

2009-08-04

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) and increased production of HIF-1alpha-responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling.

Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer.

PubMed

Choi, Ji-Yeob; Lee, Kyoung-Mu; Noh, Dong-Young; Ahn, Sei-Hyun; Lee, Jong-Eun; Han, Wonshik; Jang, In-Jin; Shin, Sang-Goo; Yoo, Keun-Young; Hayes, Richard B; Kang, Daehee

2006-11-01

The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS -786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995-2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS -786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03-4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95-10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85-3.93). The combined genotypes containing -786C or 894T was associated with a 2.5-fold risk, compared to the TT-GG genotypes, the most dominant genotype combination (95% CI = 1.29-4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31-18.36). These results indicate that the eNOS -786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors.

De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation*♦

PubMed Central

Wei, Xiaochao; Schneider, Jochen G.; Shenouda, Sherene M.; Lee, Ada; Towler, Dwight A.; Chakravarthy, Manu V.; Vita, Joseph A.; Semenkovich, Clay F.

2011-01-01

Endothelial dysfunction leads to lethal vascular complications in diabetes and related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane. In mice with endothelial inactivation of FAS (FASTie mice), eNOS membrane content and activity were decreased. eNOS and FAS were physically associated; eNOS palmitoylation was decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS-associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory state reflected as increases in vascular permeability, endothelial inflammatory markers, leukocyte migration, and susceptibility to LPS-induced death that was reversed with an NO donor. FAS-deficient endothelial cells showed deficient migratory capacity, and angiogenesis was decreased in FASTie mice subjected to hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through impaired lipogenesis identifies a novel mechanism coordinating nutritional status and tissue repair that may contribute to diabetic vascular disease. PMID:21098489

The Akt1-eNOS Axis Illustrates the Specificity of Kinase-Substrate Relationships in Vivo

PubMed Central

Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Lorenzo, Annarita Di; Harrison, Kenneth D.; Huang, Paul L.; Sessa, William C.

2016-01-01

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1−/− mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme “constitutively active” or “less active.” The eNOS mutations did not influence several phenotypes in Akt1−/− mice; however, the defective postnatal angiogenesis characteristic of Akt1−/− mice was rescued by crossing the Akt1−/− mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1α (HIF-1α) and increased production of HIF-1α–responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling. PMID:19654415

Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

PubMed

Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

2008-07-01

A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

Endovascular thoracic aortic repair and previous or concomitant abdominal aortic repair: is the increased risk of spinal cord ischemia real?

PubMed

Baril, Donald T; Carroccio, Alfio; Ellozy, Sharif H; Palchik, Eugene; Addis, Michael D; Jacobs, Tikva S; Teodorescu, Victoria; Marin, Michael L

2006-03-01

Spinal cord ischemia after endovascular thoracic aortic repair remains a significant risk. Previous or concomitant abdominal aortic repair may increase this risk. This investigation reviews the occurrence of spinal cord ischemia after endovascular repair of the descending thoracic aorta in patients with previous or concomitant abdominal aortic repair. Over an 8-year period, 125 patients underwent endovascular exclusion of the thoracic aorta at the Mount Sinai Medical Center. Twenty-eight of these patients had previous or concomitant abdominal aortic repair. The 27 patients who underwent staged repairs all had cerebrospinal fluid (CSF) drainage during and following repair. This population was analyzed for the complication of spinal cord ischemia and factors related to its occurrence. Mean follow-up was 19.3 months (range 1-61). Spinal cord ischemia developed in four of the 28 patients (14.3%) who underwent endovascular thoracic aortic repair with previous or concomitant abdominal aortic repair, while one of 97 patients (1.0%) developed ischemia among the remaining thoracic endograft population. One patient with concomitant abdominal aortic repair developed cord ischemia that manifested 12 hr following the procedure. The remaining three patients with previous abdominal aortic repair developed more delayed-onset paralysis ranging from the third postoperative day to 7 weeks following repair. Irreversible cord ischemia occurred in three patients, with full recovery in one patient. Major complications from CSF drainage occurred in one patient (3.7%). Spinal cord ischemia occurred at a markedly higher rate in patients with previous or concomitant abdominal aortic repair. This risk continued beyond the immediate postoperative period. The benefit of perioperative and salvage CSF drainage remains to be determined.

Hypoxia-induced endothelial NO synthase gene transcriptional activation is mediated through the tax-responsive element in endothelial cells.

PubMed

Min, Jiho; Jin, Yoon-Mi; Moon, Je-Sung; Sung, Min-Sun; Jo, Sangmee Ahn; Jo, Inho

2006-06-01

Although hypoxia is known to induce upregulation of endothelial NO synthase (eNOS) gene expression, the underlying mechanism is largely unclear. In this study, we show that hypoxia increases eNOS gene expression through the binding of phosphorylated cAMP-responsive element binding (CREB) protein (pCREB) to the eNOS gene promoter. Hypoxia (1% O2) increased both eNOS expression and NO production, peaking at 24 hours, in bovine aortic endothelial cells, and these increases were accompanied by increases in pCREB. Treatment with the protein kinase A inhibitor H-89 or transfection with dominant-negative inhibitor of CREB reversed the hypoxia-induced increases in eNOS expression and NO production, with concomitant inhibition of the phosphorylation of CREB induced by hypoxia, suggesting an involvement of protein kinase A/pCREB-mediated pathway. To map the regulatory elements of the eNOS gene responsible for pCREB binding under hypoxia, we constructed an eNOS gene promoter (-1600 to +22 nucleotides) fused with a luciferase reporter gene [pGL2-eNOS(-1600)]. Hypoxia (for 24-hour incubation) increased the promoter activity by 2.36+/-0.18-fold in the bovine aortic endothelial cells transfected with pGL2-eNOS(-1600). However, progressive 5'-deletion from -1600 to -873 completely attenuated the hypoxia-induced increase in promoter activity. Electrophoretic mobility shift, anti-pCREB antibody supershift, and site-specific mutation analyses showed that pCREB is bound to the Tax-responsive element (TRE) site, a cAMP-responsive element-like site, located at -924 to -921 of the eNOS promoter. Our data demonstrate that the interaction between pCREB and the Tax-responsive element site within the eNOS promoter may represent a novel mechanism for the mediation of hypoxia-stimulated eNOS gene expression.

Saxagliptin Prevents Increased Coronary Vascular Stiffness in Aortic-Banded Mini Swine.

PubMed

Fleenor, Bradley S; Ouyang, An; Olver, T Dylan; Hiemstra, Jessica A; Cobb, Melissa S; Minervini, Gianmaria; Emter, Craig A

2018-06-11

Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine. We hypothesized saxagliptin would prevent increased coronary artery stiffness in a translational swine model with cardiac features of HF with preserved ejection fraction by inhibiting perivascular adipose tissue inflammation. Yucatan mini swine were divided into 3 groups: control, aortic-banded untreated HF, and aortic-banded saxagliptin-treated HF. Ex vivo mechanical testing was performed on the left circumflex and right coronary arteries, and advanced glycation end product, NF-κB (nuclear factor-κB), and nitrotyrosine levels were measured. An increase in the coronary elastic modulus of HF animals was associated with increased vascular advanced glycation end products, NF-κB, and nitrotyrosine levels compared with control and prevented by saxagliptin treatment. Aortas from healthy mice were treated with media from swine perivascular adipose tissue culture to assess its role on vascular stiffening. Conditioned media from HF and saxagliptin-treated HF animals increased mouse aortic stiffness; however, only perivascular adipose tissue from the HF group showed increased advanced glycation end products and NF-κB levels. In conclusion, our data show increased coronary conduit vascular stiffness was prevented by saxagliptin and associated with decreased advanced glycation end products, NF-κB, and nitrotyrosine levels in a swine model with potential relevance to HF with preserved ejection fraction. © 2018 American Heart Association

Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.

PubMed

Suksawat, Manida; Techasen, Anchalee; Namwat, Nisana; Yongvanit, Puangrat; Khuntikeo, Narong; Titapun, Attapon; Koonmee, Supinda; Loilome, Watcharin

2017-08-01

Endothelial nitric oxide synthase (eNOS) is an isoform of the enzyme nitric oxide synthase (NOS) which is constitutively expressed in endothelial cells and plays important roles in vasodilation. We previously reported the importance of eNOS activation in cholangiocarcinoma (CCA) tissues and cell lines. The present study aims to investigate the relative abundance of eNOS and phosphorylated eNOS (P-eNOS) and their upstream regulators VEGFR3, VEGFC, EphA3 and ephrin-A1, in the Opisthorchis viverrini (Ov)/N-nitrosodimethylamine (NDMA)-induced hamster CCA model and in human CCA by semiquantitative immunohistochemical analysis of the relevant tissues. Results from the hamster model suggested an increase in eNOS and P-eNOS and upstream regulators during CCA genesis. In human CCA, high immunohistochemical staining intensity of all investigated proteins was associated with the presence of metastasis. A pairwise analysis of the staining data for eNOS and its upstream regulators showed that a concurrent increase in eNOS/VEGFR3, eNOS/ephrin-A1, eNOS/VEGFC and eNOS/EphA3 was significantly associated with metastasis. An increase in eNOS/VEGFR3, eNOS/ephrin-A1 was also associated with non-papillary type CCA. Additionally, an increase in eNOS and P-eNOS was significantly correlated with a high micro-vessel level (P=0.04). Our results indicate that the development of CCA involves upregulation of eNOS and P-eNOS and their regulators. This may drive angiogenesis and metastasis in CCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Space chimp Enos returns to Patrick Air Force Base

NASA Technical Reports Server (NTRS)

1961-01-01

Enos the chimpanzee that orbited the earth twice in a Mercury spacecraft arrives back at Patrick Air Force Base. Enos landed some 220 nautical miles south of Bermuda and was picked up up by the U.S.S. Stormes.

Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia.

PubMed

Kim, Joohwan; Lee, Kyu-Sun; Kim, Ji-Hee; Lee, Dong-Keon; Park, Minsik; Choi, Seunghwan; Park, Wonjin; Kim, Suji; Choi, Yoon Kyung; Hwang, Jong Yun; Choe, Jongseon; Won, Moo-Ho; Jeoung, Dooil; Lee, Hansoo; Ryoo, Sungwoo; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

2017-03-01

Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)-155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in miR-155 biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H 2 O 2 . The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent MIR155HG (miR-155 host gene) expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3'-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional miR-155 biogenesis. Thus, the redox-sensitive NF-κB/miR-155/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia. Copyright © 2017 Elsevier Inc. All rights reserved.

"Non alcoholic fatty liver disease and eNOS dysfunction in humans".

PubMed

Persico, Marcello; Masarone, Mario; Damato, Antonio; Ambrosio, Mariateresa; Federico, Alessandro; Rosato, Valerio; Bucci, Tommaso; Carrizzo, Albino; Vecchione, Carmine

2017-03-07

NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients' platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls. Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p < 0.0001). Vascular reactivity demonstrated a reduced function induced from NAFLD platelets as compared with controls (p < 0.001), associated with an impaired p-eNOS in both platelets and liver (p < 0.001). NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). In contrast with what observed in vitro, the vascular response by FMD was worse in NASH as compared with NAFL. Our data showed, for the first time in humans, that NAFLD patients show a marked eNOS dysfunction, which may contribute to a higher CV risk. eNOS dysfunction observed in platelets and liver tissue didn't match with FMD.

ENO1 Overexpression in Pancreatic Cancer Patients and Its Clinical and Diagnostic Significance

PubMed Central

Yin, Hang; Wang, Lei

2018-01-01

We investigated in this study the expression of ENO1 in tissues and plasma of PDAC patients to evaluate its clinicopathological and diagnostic significance. ENO1 protein expression was detected in tissue microarray of human PDAC and adjacent noncancer tissues. Electrochemiluminescence immunoassay and amplified luminescent proximity homogeneous assay (AlphaLISA) were performed to measure CA19-9 and ENO1 concentration in plasma from PDAC patients and healthy controls. We demonstrated that ENO1 overexpression is positively correlated with clinical stage, lymph node metastasis, and poor prognosis of PDAC; ENO1 may function as a hopeful candidate diagnostic marker in combination with CA19-9 in PDAC diagnosis. PMID:29483925

enoLOGOS: a versatile web tool for energy normalized sequence logos

PubMed Central

Workman, Christopher T.; Yin, Yutong; Corcoran, David L.; Ideker, Trey; Stormo, Gary D.; Benos, Panayiotis V.

2005-01-01

enoLOGOS is a web-based tool that generates sequence logos from various input sources. Sequence logos have become a popular way to graphically represent DNA and amino acid sequence patterns from a set of aligned sequences. Each position of the alignment is represented by a column of stacked symbols with its total height reflecting the information content in this position. Currently, the available web servers are able to create logo images from a set of aligned sequences, but none of them generates weighted sequence logos directly from energy measurements or other sources. With the advent of high-throughput technologies for estimating the contact energy of different DNA sequences, tools that can create logos directly from binding affinity data are useful to researchers. enoLOGOS generates sequence logos from a variety of input data, including energy measurements, probability matrices, alignment matrices, count matrices and aligned sequences. Furthermore, enoLOGOS can represent the mutual information of different positions of the consensus sequence, a unique feature of this tool. Another web interface for our software, C2H2-enoLOGOS, generates logos for the DNA-binding preferences of the C2H2 zinc-finger transcription factor family members. enoLOGOS and C2H2-enoLOGOS are accessible over the web at . PMID:15980495

Decreased expression of fibulin-4 in aortic wall of aortic dissection.

PubMed

Huawei, P; Qian, C; Chuan, T; Lei, L; Laing, W; Wenlong, X; Wenzhi, L

2014-02-01

In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177.

PubMed

Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N; Wakula, Paulina; Groschner, Klaus; Maier, Lars S; Spiess, Joachim; Blatter, Lothar A; Pieske, Burkert; Kockskämper, Jens

2014-09-01

Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. Copyright © 2014 the American Physiological Society.

Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

PubMed Central

Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

2009-01-01

Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation

PubMed Central

Wang, Mingming; Chen, Minchun; Ding, Yi; Zhu, Zhihui; Zhang, Yikai; Wei, Peifeng; Wang, Jingwen; Qiao, Yi; Li, Liang; Li, Yuwen; Wen, Aidong

2015-01-01

Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3’, 5’-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway. PMID:26482008

(−)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells

PubMed Central

Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo

2011-01-01

The consumption of cacao-derived (i.e., cocoa) products provides beneficial cardiovascular effects in healthy subjects as well as individuals with endothelial dysfunction such as smokers, diabetics, and postmenopausal women. The vascular actions of cocoa are related to enhanced nitric oxide (NO) production. These actions can be reproduced by the administration of the cacao flavanol (−)-epicatechin (EPI). To further understand the mechanisms behind the vascular action of EPI, we investigated the effects of Ca2+ depletion on endothelial nitric oxide (NO) synthase (eNOS) activation/phosphorylation and translocation. Human coronary artery endothelial cells were treated with EPI or with bradykinin (BK), a well-known Ca2+-dependent eNOS activator. Results demonstrate that both EPI and BK induce increases in intracellular calcium and NO levels. However, under Ca2+-free conditions, EPI (but not BK) is still capable of inducing NO production through eNOS phosphorylation at serine 615, 633, and 1177. Interestingly, EPI-induced translocation of eNOS from the plasmalemma was abolished upon Ca2+ depletion. Thus, under Ca2+-free conditions, EPI can stimulate NO synthesis independent of calmodulin binding to eNOS and of its translocation into the cytoplasm. We also examined the effect of EPI on the NO/cGMP/vasodilator-stimulated phosphoprotein (VASP) pathway activation in isolated Ca2+-deprived canine mesenteric arteries. Results demonstrate that under these conditions, EPI induces the activation of this vasorelaxation-related pathway and that this effect is inhibited by pretreatment with nitro-l-arginine methyl ester, suggesting a functional relevance for this phenomenon. PMID:21209365

Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms.

PubMed

Albini, Paul T; Segura, Ana Maria; Liu, Guanghui; Minard, Charles G; Coselli, Joseph S; Milewicz, Dianna M; Shen, Ying H; LeMaire, Scott A

2014-02-01

The pathogenesis of non-familial, sporadic ascending aortic aneurysms (SAAA) is poorly understood, and the relationship between ascending aortic atherosclerosis and medial degeneration is unclear. We evaluated the prevalence and severity of aortic atherosclerosis and its association with medial degeneration in SAAA. Atherosclerosis was characterized in ascending aortic tissues collected from 68 SAAA patients (mean age, 62.9 ± 12.0 years) and 15 controls (mean age, 56.6 ± 11.4 years [P = 0.07]) by using a modified American Heart Association classification system. Upon histologic examination, 97% of SAAA patients and 73% of controls showed atherosclerotic changes. Most SAAA samples had intermediate (types 2 and 3, 35%) or advanced atherosclerosis (types ≥ 4; 40%), whereas most control samples showed minimal atherosclerosis (none or type 1, 80%; P < 0.001 after adjusting for age). In a separate analysis, we examined the total incidence and grade distribution of medial degenerative changes among SAAA samples according to atherosclerosis grade. Advanced atherosclerosis was associated with higher grades of smooth muscle cell depletion (P < 0.001), elastic fiber depletion (P = 0.02), elastic fiber fragmentation (P < 0.001), and mucopolysaccharide accumulation (P = 0.04). Aortic diameter was larger in SAAA patients with advanced atherosclerosis than in patients with minimal (P = 0.04) or intermediate atherosclerosis (P = 0.04). Immunostaining showed marked CD3+ T-cell and CD68+ macrophage infiltration, MMP-2 and MMP-9 production, and cryopyrin expression in the medial layer adjacent to atherosclerotic plaque. SAAA tissues exhibited advanced atherosclerosis that was associated with severe medial degeneration and increased aortic diameter. Our findings suggest a role for atherosclerosis in the progression of sporadic ascending aortic aneurysms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.

PubMed

Huk, Danielle J; Hammond, Harriet L; Kegechika, Hiroyuki; Lincoln, Joy

2013-02-01

Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

Morus alba extract modulates blood pressure homeostasis through eNOS signaling.

PubMed

Carrizzo, Albino; Ambrosio, Mariateresa; Damato, Antonio; Madonna, Michele; Storto, Marianna; Capocci, Luca; Campiglia, Pietro; Sommella, Eduardo; Trimarco, Valentina; Rozza, Francesco; Izzo, Raffaele; Puca, Annibale A; Vecchione, Carmine

2016-10-01

Morus alba is a promising phytomedicine cultivated in oriental countries that is extensively used to prevent and treat various cardiovascular problems. To date, despite its beneficial effects, the molecular mechanisms involved remain unclear. Thus, we investigate the vascular and haemodynamic effects of Morus alba extract in an experimental model focusing our attention on the molecular mechanisms involved. Through vascular reactivity studies, we demonstrate that Morus alba extract evokes endothelial vasorelaxation through a nitric oxide-dependent pathway. Our molecular analysis highlights an increase in endothelial nitric oxide synthase (eNOS) phosphorylation. In vivo administration of Morus alba extract reduces blood pressure levels exclusively in wild-type mice, whereas it fails to evoke any haemodynamic effects in eNOS-deficient mice. Molecular analyses revealed that its beneficial action on vasculature is mediated by the activation of two important proteins that act as stress sensors and chaperones: PERK and heat shock protein 90. Finally, Morus alba extract exerts antihypertensive action in an experimental model of arterial hypertension. Through its action on eNOS signaling, Morus alba extract could act as a food supplement for the regulation of cardiovascular system, mainly in clinical conditions characterized by eNOS dysfunction, such as arterial hypertension. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the application of ENO scheme with subcell resolution to conservation laws with stiff source terms

NASA Technical Reports Server (NTRS)

Chang, Shih-Hung

1991-01-01

Two approaches are used to extend the essentially non-oscillatory (ENO) schemes to treat conservation laws with stiff source terms. One approach is the application of the Strang time-splitting method. Here the basic ENO scheme and the Harten modification using subcell resolution (SR), ENO/SR scheme, are extended this way. The other approach is a direct method and a modification of the ENO/SR. Here the technique of ENO reconstruction with subcell resolution is used to locate the discontinuity within a cell and the time evolution is then accomplished by solving the differential equation along characteristics locally and advancing in the characteristic direction. This scheme is denoted ENO/SRCD (subcell resolution - characteristic direction). All the schemes are tested on the equation of LeVeque and Yee (NASA-TM-100075, 1988) modeling reacting flow problems. Numerical results show that these schemes handle this intriguing model problem very well, especially with ENO/SRCD which produces perfect resolution at the discontinuity.

Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

PubMed Central

Harvey, Nicholas C.; Lillycrop, Karen A.; Garratt, Emma; Sheppard, Allan; McLean, Cameron; Burdge, Graham; Slater-Jefferies, Jo; Rodford, Joanne; Crozier, Sarah; Inskip, Hazel; Emerald, Bright Starling; Gale, Catharine R; Hanson, Mark; Gluckman, Peter; Godfrey, Keith; Cooper, Cyrus

2013-01-01

Aim Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children. Methods We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Results Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Conclusions Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development. PMID:22159788

Gender, exercise training, and eNOS expression in porcine skeletal muscle arteries.

PubMed

Laughlin, M Harold; Welshons, Wade V; Sturek, Michael; Rush, James W E; Turk, James R; Taylor, Julia A; Judy, Barbara M; Henderson, Kyle K; Ganjam, V K

2003-07-01

Our purpose was to determine the effects of gender and exercise training on endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) protein content of porcine skeletal muscle arteries and to evaluate the role of 17beta-estradiol (E2) in these effects. We measured eNOS and SOD content with immunoblots and immunohistochemistry in femoral and brachial arteries of trained and sedentary male and female pigs and measured estrogen receptor (ER) mRNA and alpha-ER and beta-ER protein in aortas of male and female pigs. Results indicate that female arteries contain more eNOS than male arteries and that exercise training increases eNOS content independent of gender. Male and female pigs expressed similar levels of alpha-ER mRNA and protein and similar amounts beta-ER protein in their arteries. E2 concentrations as measured by RIA were 180 +/- 34 pg/ml in male sera and approximately 5 pg/ml in female sera, and neither was changed by training. However, bioassay indicated that biologically active estrogen equivalent to only 35 +/- 5 pg/ml was present in male sera. E2 in female pigs, whether measured by RIA or bioassay, was approximately 24 pg/ml at peak estrous and 2 pg/ml on day 5 diestrus. The free fraction of E2 in sera did not explain the low measurements, relative to RIA, of E2. We conclude that 1). gender has significant influence on eNOS and SOD content of porcine skeletal muscle arteries; 2). the effects of gender and exercise training vary among arteries of different anatomic origin; 3). male sera contains compounds that cause RIA to overestimate circulating estrogenic activity; and 4). relative to human men, the male pig is not biologically estrogenized by high levels of E2 reported by RIA, whereas in female pigs E2 levels are lower than in the blood of human women.

Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves.

PubMed

Saikrishnan, Neelakantan; Mirabella, Lucia; Yoganathan, Ajit P

2015-06-01

Congenital bicuspid aortic valves (BAVs) are associated with accelerated disease progression, such as leaflet calcification and ascending aorta dilatation. Although common underlying genetic factors have been implicated in accelerated disease in BAV patients, several studies have suggested that altered hemodynamics also play a role in this disease process. The present study compares turbulence and wall shear stress (WSS) measurements between various BAV and trileaflet aortic valve (TAV) models to provide information for mechanobiological models of BAV disease. BAV and TAV models were constructed from excised porcine aortic valves to simulate parametric variations in BAV stenosis, hemodynamics and geometry. Particle image velocimetry experiments were conducted at physiological pressure conditions to characterize velocity fields in the ascending aorta. The velocity fields were post-processed to calculate turbulence, viscous and wall shear stresses in the ascending aorta. Stenosed BAV models showed the presence of eccentric systolic jets, causing increased WSS. Lower cardiac output resulted in a narrower jet, lower turbulence and lower viscous shear stress (VSS). The specific severe stenosis BAV model studied here showed reduced WSS due to reduction in non-fused leaflet mobility. Dilation of the aorta did not affect any turbulence or VSS, but reduced the WSS. In comparison with BAVs, TAVs have similar VSS values, but much smaller WSS and turbulence levels. These increased turbulence  and WSS levels in BAVs may play a key role in amplifying the biological responses of the ascending aorta wall and valvular leaflets, and support the hemodynamic underpinnings of BAV disease processes.

eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation.

PubMed

Karbach, Susanne; Wenzel, Philip; Waisman, Ari; Munzel, Thomas; Daiber, Andreas

2014-01-01

Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature.

Differential effects of eNOS uncoupling on conduit and small arteries in GTP-cyclohydrolase I-deficient hph-1 mice.

PubMed

d'Uscio, Livius V; Smith, Leslie A; Katusic, Zvonimir S

2011-12-01

In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin (BH(4)) in conduit and small arteries activates compensatory mechanisms designed to protect vascular wall from oxidative stress induced by uncoupling of endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels were reduced in the aortas and small mesenteric arteries of hph-1 mice. However, the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1 aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were significantly enhanced in aortas but not in small mesenteric arteries of hph-1 mice. In contrast to the aorta, protein expression of copper- and zinc-containing superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric arteries of hph-1 mice. Protein expression of catalase was increased in both aortas and small mesenteric arteries of hph-1 mice. Further analysis of endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas. Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the most likely mechanism responsible for phosphorylation of eNOS and elevation of cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is sufficient to protect vascular tissue from increased production of reactive oxygen species generated by uncoupling of eNOS. The results of our study suggest that anatomical origin determines the ability of vessel wall to cope with oxidative stress induced by uncoupling of eNOS.

Aortic Dissection in Patients With Bicuspid Aortic Valve–Associated Aneurysms

PubMed Central

Wojnarski, Charles M.; Svensson, Lars G.; Roselli, Eric E.; Idrees, Jay J.; Lowry, Ashley M.; Ehrlinger, John; Pettersson, Gösta B.; Gillinov, A. Marc; Johnston, Douglas R.; Soltesz, Edward G.; Navia, Jose L.; Hammer, Donald F.; Griffin, Brian; Thamilarasan, Maran; Kalahasti, Vidyasagar; Sabik, Joseph F.; Blackstone, Eugene H.; Lytle, Bruce W.

2016-01-01

Background Data regarding the risk of aortic dissection in patients with bicuspid aortic valve and large ascending aortic diameter are limited, and appropriate timing of prophylactic ascending aortic replacement lacks consensus. Thus our objectives were to determine the risk of aortic dissection based on initial cross-sectional imaging data and clinical variables and to isolate predictors of aortic intervention in those initially prescribed serial surveillance imaging. Methods From January 1995 to January 2014, 1,181 patients with bicuspid aortic valve underwent cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI) to ascertain sinus or tubular ascending aortic diameter greater than or equal to 4.7 cm. Random Forest classification was used to identify risk factors for aortic dissection, and among patients undergoing surveillance, time-related analysis was used to identify risk factors for aortic intervention. Results Prevalence of type A dissection that was detected by imaging or was found at operation or on follow-up was 5.3% (n = 63). Probability of type A dissection increased gradually at a sinus diameter of 5.0 cm—from 4.1% to 13% at 7.2 cm—and then increased steeply at an ascending aortic diameter of 5.3 cm—from 3.8% to 35% at 8.4 cm—corresponding to a cross-sectional area to height ratio of 10 cm2/m for sinuses of Valsalva and 13 cm2/m for the tubular ascending aorta. Cross-sectional area to height ratio was the best predictor of type A dissection (area under the curve [AUC] = 0.73). Conclusions Early prophylactic ascending aortic replacement in patients with bicuspid aortic valve should be considered at high-volume aortic centers to reduce the high risk of preventable type A dissection in those with aortas larger than approximately 5.0 cm or with a cross-sectional area to height ratio greater than approximately 10 cm2/m. PMID:26209494

Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1.

PubMed

Jiang, Rujia; Hodgson, Jonathan M; Mas, Emilie; Croft, Kevin D; Ward, Natalie C

2016-01-01

Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1. Copyright © 2015 Elsevier Inc. All rights reserved.

Murine study of portal hypertension associated endothelin-1 hypo-response.

PubMed

Theodorakis, Nicholas; Maluccio, Mary; Skill, Nicholas

2015-04-28

To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes. Wild type, eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to induce portal hypertension or sham surgery. Development of portal hypertension was determined by measuring the splenic pulp pressure, abdominal aortic flow and portal systemic shunting. To measure splenic pulp pressure, a microtip pressure transducer was inserted into the spleen pulp. Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery. Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration. In addition, thoracic aorta endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph. In wild type and iNOS(-/-) mice splenic pulp pressure increased from 7.5 ± 1.1 mmHg and 7.2 ± 1 mmHg to 25.4 ± 3.1 mmHg and 22 ± 4 mmHg respectively. In eNOS(-/-) mice splenic pulp pressure was increased after 1 d (P = NS), after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls (6.9 ± 0.6 mmHg and 7.3 ± 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when compared to shams, whereas there was no significant difference in 7 d portal vein ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-) sham mice (50% ± 8%, 73% ± 9% and 47% ± 9% respectively). Following portal vein ligation endothelin-1 reduction in blood flow

PGC-1α dictates endothelial function through regulation of eNOS expression

PubMed Central

Craige, Siobhan M.; Kröller-Schön, Swenja; Li, Chunying; Kant, Shashi; Cai, Shenghe; Chen, Kai; Contractor, Mayur M.; Pei, Yongmei; Schulz, Eberhard; Keaney, John F.

2016-01-01

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1α sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1α EC TG mice were protected. Mechanistically, PGC-1α promotes eNOS expression and activity, which is necessary for protection from ATII-induced dysfunction as mice either treated with an eNOS inhibitor (LNAME) or lacking eNOS were no longer responsive to transgenic endothelial PGC-1α expression. Finally, we determined that the orphan nuclear receptor, estrogen related receptor α (ERRα) is required to coordinate the PGC-1α -induced eNOS expression. In conclusion, endothelial PGC-1α expression protects from vascular dysfunction by promoting NO• bioactivity through ERRα induced expression of eNOS. PMID:27910955

Sildenafil Promotes eNOS Activation and Inhibits NADPH Oxidase in the Transgenic Sickle Cell Mouse Penis

PubMed Central

Musicki, Biljana; Bivalacqua, Trinity J.; Champion, Hunter C.; Burnett, Arthur L.

2014-01-01

Introduction Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. Aims We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. Methods SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Main Outcome Measures Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Results Continuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P-eNOS (Ser-1177), eNOS/HSP90 interaction, P-AKT, protein expression of gp91(phox), and 4-HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters. Conclusion Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. PMID:24251665

Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis.

PubMed

Musicki, Biljana; Bivalacqua, Trinity J; Champion, Hunter C; Burnett, Arthur L

2014-02-01

Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Continuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P-eNOS (Ser-1177), eNOS/HSP90 interaction, P-AKT, protein expression of gp91(phox), and 4-HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters. Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. © 2013 International Society for Sexual Medicine.

Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

PubMed Central

Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

2013-01-01

Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

Physical Fitness and Aortic Stiffness Explain the Reduced Cognitive Performance Associated with Increasing Age in Older People.

PubMed

Kennedy, Greg; Meyer, Denny; Hardman, Roy J; Macpherson, Helen; Scholey, Andrew B; Pipingas, Andrew

2018-01-01

Greater physical fitness is associated with reduced rates of cognitive decline in older people; however, the mechanisms by which this occurs are still unclear. One potential mechanism is aortic stiffness, with increased stiffness resulting in higher pulsatile pressures reaching the brain and possibly causing progressive micro-damage. There is limited evidence that those who regularly exercise may have lower aortic stiffness. To investigate whether greater fitness and lower aortic stiffness predict better cognitive performance in older people and, if so, whether aortic stiffness mediates the relationship between fitness and cognition. Residents of independent living facilities, aged 60-90, participated in the study (N = 102). Primary measures included a computerized cognitive assessment battery, pulse wave velocity analysis to measure aortic stiffness, and the Six-Minute Walk test to assess fitness. Based on hierarchical regression analyses, structural equation modelling was used to test the mediation hypothesis. Both fitness and aortic stiffness independently predicted Spatial Working Memory (SWM) performance, however no mediating relationship was found. Additionally, the derived structural equation model shows that, in conjunction with BMI and sex, fitness and aortic stiffness explain 33% of the overall variation in SWM, with age no longer directly predicting any variation. Greater fitness and lower aortic stiffness both independently predict better SWM in older people. The strong effect of age on cognitive performance is totally mediated by fitness and aortic stiffness. This suggests that addressing both physical fitness and aortic stiffness may be important to reduce the rate of age associated cognitive decline.

Association of eNOS and ACE gene polymorphisms and plasma nitric oxide with risk of non-small cell lung cancer in South India.

PubMed

Peddireddy, Vidyullatha; Badabagni, Siva Prasad; Gundimeda, Sandhya Devi; Mundluru, Hema Prasad

2018-01-01

The role of ACE and eNOS gene polymorphisms and their association with various cancers were reported. However, their role in the lung cancer is unclear. In this study, we analyzed eNOS and ACE gene polymorphisms and the risk of non-small cell lung cancer (NSCLC) in South Indian population. For the eNOS gene, the homozygous "AA" genotypic frequency was significantly associated with NSCLC with an overall risk of 3.6-fold (P = 0.006, odds ratio = 3.58, 95% confidence interval = 1.66, 7.723). The heterozygous "I/D" genotypic frequency of ACE gene was significantly higher in NSCLC patients when compared to the controls with a 2.29-fold risk for NSCLC. Multiple regression analyses indicated that gender, smoking status, and polymorphisms in eNOS and ACE genes as the strongest predicting factors for an increased susceptibility to NSCLC. We report for the first time that polymorphisms in the eNOS "A/A" (homozygous mutant) and ACE "I/D" genotypes might contribute to the increased risk of NSCLC in the South Indian population. © 2016 John Wiley & Sons Ltd.

Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

NASA Technical Reports Server (NTRS)

Woodman, C. R.; Schrage, W. G.; Rush, J. W.; Ray, C. A.; Price, E. M.; Hasser, E. M.; Laughlin, M. H.

2001-01-01

We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

Positive family history of aortic dissection dramatically increases dissection risk in family members.

PubMed

Ma, Wei-Guo; Chou, Alan S; Mok, Salvior C M; Ziganshin, Bulat A; Charilaou, Paris; Zafar, Mohammad A; Sieller, Richard S; Tranquilli, Maryann; Rizzo, John A; Elefteriades, John A

2017-08-01

Although family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives. Patients with AoD at our institution were analyzed for information of FHAD. Positive FHAD referred to that AoD occurred in index patient and one or more first-degree relatives. Negative FHAD was defined as the condition in which only one case of AoD (the index patient) occurred in the family. The age at AoD, exposure years in adulthood before AoD, and annual probability of AoD among first-degree relatives were compared between patients with negative and positive FHADs. FHAD was positive in 32 and negative in 68 among the 100 AoD patients with detailed family history information. Mean age at dissection was 59.9±14.7years. Compared to negative FHAD, patients with positive FHAD dissected at significantly younger age (54.7±16.8 vs 62.4±13.0years, p=0.013), had more AoD events in first-degree relatives (2.3±0.6 vs 1.0±0.0, p<0.001), and shorter exposure years per AoD event (18.3±6.7 vs 43.1±8.5, p<0.001). Annual probability of AoD per first-degree relative was 2.77 times higher in patients with positive than negative FHADs (0.0100±0.0057 vs 0.0036±0.0014, p<0.001). A positive FHAD confers a significantly increased risk of developing aortic dissection on family members, with a higher annual probability of aortic dissection, a shorter duration of "exposure time" before dissection occurs and a lower mean age at time of dissection. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

INCREASED HYPOTHALAMIC ANGIOTENSIN-(1-7) LEVELS IN RATS WITH AORTIC COARCTATION-INDUCED HYPERTENSION

PubMed Central

Gironacci, Mariela M.; Brosnihan, K. Bridget; Ferrario, Carlos M.; Gorzalczany, Susana; Lopez Verrilli, María A.; Pascual, Mariano; Taira, Carlos; Peña, Clara

2007-01-01

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process. PMID:17646033

Aortic stiffness increases in proportion to the severity of apnoea-hypopnea index in patients with obstructive sleep apnoea syndrome.

PubMed

Çörtük, Mustafa; Akyol, Selahattin; Baykan, Ahmet O; Kiraz, Kemal; Uçar, Hakan; Çaylı, Murat; Kandiş, Hayati

2016-07-01

Obstructive sleep apnoea syndrome (OSA) and aortic stiffness are associated with an increased risk of cardiovascular morbidity and mortality. Although aortic stiffness increased in patients with OSA, the relationship between severity of OSA indicated with apnoea-hypopnea index (AHI) and aortic stiffness was not investigated in previous studies. The aim of this study is to investigate the relationship between the severity of OSA and aortic stiffness. In the present study, 90 consecutive OSA patients definite diagnosed with sleep test were prospectively included (mean age 54.5 ± 11.6 years). Aortic pulse wave velocity (PWV) and augmentation index (AIx) were calculated using the single-point method via the Mobil-O-Graph® ARCsolver algorithm. Aortic distensibility (AD) was calculated from the echocardiographically derived ascending aorta diameters and haemodynamic pressure measurements. Overnight full-laboratory polysomnography examination was conducted on each subject. Patients were classified into two groups according to their median AHI values (AHIlow and AHIhigh groups). PWV values were higher and AD values were lower in AHIhigh group compared with AHIlow group (P < 0.05, for all). AHI was associated with body mass index (BMI), systolic blood pressure, pulse pressure, aortic diameter, AD, AIx and PWV in bivariate analysis (P < 0.05, for all). Multivariate linear regression analysis showed that AHI was independently associated with BMI (β = 0.175, P = 0.047), PWV (β = 0.521, P < 0.001) and aortic distensibility (β = -0.223, P = 0.020). Aortic stiffness is associated both with the presence and the severity of OSA. © 2014 John Wiley & Sons Ltd.

Effects of hyperbaric oxygen therapy in enhancing expressions of e-NOS, TNF-α and VEGF in wound healing

NASA Astrophysics Data System (ADS)

Susilo, Imam; Devi, Anita; Purwandhono, Azham; Hadi Warsito, Sunaryo

2017-05-01

Wound healing is a physiological process that occurs progressively through overlapping phases. Tissue oxygenation is an important part of the complex regulation for wound healing. Hyperbaric Oxygen (HBO) therapy is a method of increasing oxygen delivery to tissues. The therapy improves tissue oxygenation and stimulates the formation of H2O2 as a secondary messenger for Tumour Necrosis Factor alpha (TNF α), e-NOS, VEGF and Nuclear Factor Kappa Beta phosphorylation (NF-Kb) which play an important role in the rapid transcription of a wide variety of genes in response to extracellular stimuli. This study aims to determine the effects of Hyperbaric Oxygen therapy in enhancing the expressions of e-NOS, TNF-α, VEGF and wound healing. This study is an animal study with a ‘randomized control group of pre-test and post test design’ on 28 Wistar rats. Randomly, the rats were divided into 4 groups with 7 rats in each group. The HBO treatment group 1 received 5 sessions of HBO 2.4 ATA in 3 × 30 minutes; the HBO treatment group 2 received 10 sessions of HBO 2.4 ATA in 3 × 30 minutes; and each of the control groups were without HBO. Each of the 28 male rats were given a full thickness excisional wound of 1 × 1cm. Examinations of e-NOS, TNF-α, VEGF expressions and wound healing were performed on day-0 (pre-HBO) and day-5 HBO or on day-0 (pre-HBO) and day-10 HBO. The resultsshowthat the Hyperbaric Oxygen therapy can improve e-NOS (p=0.02), TNF-α (p= 0.02), VEGF expression (p=0.02) and wound healing (p=0.002) significantly in the provision of HBO 2.4 ATA for 3 × 30 minutes in 5 sessions over 5 consecutive days. While the 10 sessions of HBO 2.4 ATA for 3 × 30 minutes over 10 consecutive days only increase e-NOS (p=0.02), TNF-α (p=0.04), VEGF expression significantly (p=0.03) but do not improve wound healing significantly (p=0.3) compared with no HBO. The study concludes that HBO can improve the expressions of e-NOS, TNF-α, VEGF and wound healing in the provision of HBO

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation.

PubMed

Dias, Rodrigo G; Alves, Maria-Janieire N N; Pereira, Alexandre C; Rondon, Maria Urbana P B; Dos Santos, Marcelo R; Krieger, José E; Krieger, Marta H; Negrão, Carlos E

2009-04-10

The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not

Spectrum of Aortic Valve Abnormalities Associated with Aortic Dilation Across Age Groups in Turner Syndrome

PubMed Central

Olivieri, Laura J.; Baba, Ridhwan Y.; Arai, Andrew E.; Bandettini, W. Patricia; Rosing, Douglas R.; Bakalov, Vladimir; Sachdev, Vandana; Bondy, Carolyn A.

2014-01-01

Background Congenital aortic valve fusion is associated with aortic dilation, aneurysm and rupture in girls and women with Turner syndrome (TS). Our objective was to characterize aortic valve structure in subjects with TS, and determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves. Methods and Results The aortic valve and thoracic aorta were characterized by cardiovascular magnetic resonance imaging in 208 subjects with TS in an IRB-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve, and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve (TAV) 64%(n=133), partially fused aortic valve (PF) 12%(n=25), bicuspid aortic valve (BAV) 23%(n=47), and unicuspid aortic valve (UAV) 1%(n=3). Age and body surface area (BSA) were similar in the 4 valve morphology groups. There was a significant trend, independent of age, towards larger BSA-indexed ascending aortic diameters (AADi) with increasing valve fusion. AADi were (mean +/− SD) 16.9 +/− 3.3 mm/m2, 18.3 +/− 3.3 mm/m2, and 19.8 +/− 3.9 mm/m2 (p<0.0001) for TAV, PF and BAV+UAV respectively. PF, BAV, and UAV were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve. Conclusions Aortic valve abnormalities in TS occur with a spectrum of severity, and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased AADi. PMID:24084490

Identification and Function Analysis of enolase Gene NlEno1 from Nilaparvata lugens (Stål) (Hemiptera:Delphacidae)

PubMed Central

Wang, Wei-Xia; Li, Kai-Long; Chen, Yang; Lai, Feng-Xiang; Fu, Qiang

2015-01-01

The enolase [EC 4.2.1.11] is an essential enzyme in the glycolytic pathway catalyzing the conversion of 2-phosphoglycerate (2-PGE) to phosphoenolpyruvate (PEP). In this study, a full-length cDNA encoding α-enolase was cloned from rice brown planthopper (Nilaparvata lugens) and is provisionally designated as NlEno1. The cDNA sequence of NlEno1 was 1,851 bp with an open reading frame (ORF) of 1,305 bp and encoding 434 amino acids. The deduced protein shares high identity of 80–87% with ENO1-like protein from Hemiptera, Diptera, and Lepidoptera speices. The NlEno1 showed the highest mRNA expression level in hemolymph, followed by fat body, salivary gland, ovaries and egg, and showed trace mRNA levels in testis. The mRNA of NlEno1 showed up-regulated level in virulent N. lugens population Mudgo, IR56 and IR42 when compared with TN1 population. Injection of double-stranded RNA (dsRNA) of NlEno1 into the adults significantly down-regulated the NlEno1 mRNA level along with decreased eggs and offspring. Moreover, injection of NlEno1-dsRNA decreased mRNA level of Vitellogenin (Vg) gene. These results showed that the NlEno1, as a key glycolytic enzyme, may play roles in regulation of fecundity and adaptation of N. lugens to resistant rice varieties. PMID:26056319

Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase

PubMed Central

Musicki, Biljana; Liu, Tongyun; Lagoda, Gwen A.; Strong, Travis D.; Sezen, Sena F.; Johnson, Justin M.; Burnett, Arthur L.

2010-01-01

INTRODUCTION Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood. AIMS We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED. METHODS Low-density-lipoprotein receptor (LDLR)–null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67phox, p47phox, and gp91phox), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes. MAIN OUTCOME MEASURES Molecular mechanisms of ROS generation and endothelial dysfunction in hypercholesterolemia-induced ED. RESULTS Erectile response was significantly (P<0.05) reduced in hypercholesterolemic LDLR-null mice compared to WT mice. Relative to WT mice, hypercholesterolemia increased (P<0.05) protein expressions of NAD(P)H oxidase subunits p67phox, p47phox and gp91phox, eNOS uncoupling, and 4-HNE-modified proteins, and reduced (P<0.05) P-VASP-Ser-239 expression in the penis. Apocynin treatment of LDLR-null mice preserved (P<0.05) maximal intracavernosal pressure, and reversed (P < 0.05) the abnormalities in protein expressions of gp67phox and gp47phox, 4-HNE, P-VASP-Ser-239, and eNOS uncoupling in the penis. Apocynin treatment of WT mice did not affect any of these parameters

Decreased poststenotic flow disturbance during drag reduction by polyacrylamide infusion without increased aortic blood flow.

PubMed

Hutchison, K J; Campbell, J D; Karpinski, E

1989-07-01

The infusion of polyacrylamide in open chest rats has been reported to increase aortic blood flow and the effect has been ascribed to the "drag reduction" properties of these compounds. In six anesthetized dogs the infusion of polyacrylamide to a total dose of 2 mg/kg caused a reduction in midline and separation zone Doppler spectral broadening in the common carotid artery poststenotic velocity field. This apparent reduction in poststenotic turbulence was interpreted as indicating the presence of a drag reducing effect. Despite this demonstration that polyacrylamide was present in the blood in drag reducing concentrations no increase in aortic blood flow was produced.

Magnolol Administration in Normotensive Young Spontaneously Hypertensive Rats Postpones the Development of Hypertension: Role of Increased PPAR Gamma, Reduced TRB3 and Resultant Alleviative Vascular Insulin Resistance

PubMed Central

Fu, Feng; Zhang, Wei; Su, Feifei; Liu, Fange; Ji, Lele; Gao, Feng; Su, Hui; Sun, Xin; Zhang, Haifeng

2015-01-01

Patients with prehypertension are more likely to progress to manifest hypertension than those with optimal or normal blood pressure. However, the mechanisms underlying the development from prehypertension to hypertension still remain largely elusive and the drugs for antihypertensive treatment in prehypertension are absent. Here we determined the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin, and investigated the underlying mechanisms. Four-week-old male spontaneous hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. Our results shown that treatment of young SHRs with MAG (100 mg/kg/day, o.g.) for 3 weeks decreased blood pressure, improved insulin-induced aorta vasodilation, restored Akt and eNOS activation stimulated by insulin, and increased PPARγ and decreased TRB3 expressions. In cultured human umbilical vein endothelial cells (HUVECs), MAG incubation increased PPARγ, decreased TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels and NO production, which was blocked by both PPARγ antagonist and siRNA targeting PPARγ. Improved insulin signaling in HUVECs by MAG was abolished by upregulating TRB3 expression. In conclusion, treatment of young SHRs with MAG beginning at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to upregulated PPARγ, downregulated TRB3 and consequently increased Akt and eNOS activations in blood vessels in SHRs. PMID:25793876

SMAD4 gene mutation increases the risk of aortic dilation in patients with hereditary haemorrhagic telangiectasia.

PubMed

Vorselaars, V M M; Diederik, A; Prabhudesai, V; Velthuis, S; Vos, J-A; Snijder, R J; Westermann, C J J; Mulder, B J; Ploos van Amstel, J K; Mager, J J; Faughnan, M E; Post, M C

2017-10-15

Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls. Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area. In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (β-coefficient 3.5, p<0.001) and ascending aorta diameter (β-coefficient 1.6, p=0.04). SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

PubMed

Tastekin, Ebru; Palabiyik, Orkide; Ulucam, Enis; Uzgur, Selda; Karaca, Aziz; Vardar, Selma Arzu; Yilmaz, Ali; Aydogdu, Nurettin

2016-08-01

Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies.

Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice.

PubMed

Mahmood, Qaisar; Wang, Guang-Fa; Wu, Gang; Wang, Huan; Zhou, Chang-Xin; Yang, Hong-Yu; Liu, Zhi-Rong; Han, Feng; Zhao, Kui

2017-02-15

Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min. High-resolution positron emission tomography scanner (micro-PET) was used for small animal imaging to examine glucose metabolism. Rota-rod time and neurological deficit scores were calculated after 24h of reperfusion. The volume of infarction was determined by Nissl-staining. The calpain proteolytic activity and eNOS uncoupling were determined by western blot analysis. SAA administration increased glucose metabolism and ameliorated neuronal damage after brain ischemia, paralleled with decreased neurological deficit and volume of infarction. In addition, SAA pretreatment inhibited eNOS uncoupling and calpain proteolytic activity. Furthermore, SAA inhibited peroxynitrite (ONOO - ) generation and upregulates AKT, FKHR and ERK phosphorylation. These findings strongly suggest that SAA elicits a neurovascular protective role through the inhibition of eNOS uncoupling and ONOO - formation. Moreover, SAA attenuates spectrin and calcineurin breakdown and therefore protects the brain against ischemic/reperfusion injury. Copyright © 2016 Elsevier GmbH. All rights reserved.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

PubMed

Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Hemiarch Reconstruction Vs Clamped Aortic Anastomosis for Concomitant Ascending Aortic Aneurysm.

PubMed

Sultan, Ibrahim; Bianco, Valentino; Yajzi, Ibrahim; Kilic, Arman; Dufendach, Keith; Cardounel, Arturo; Althouse, Andrew D; Masri, Ahmad; Navid, Forozan; Gleason, Thomas G

2018-05-03

Deep hypothermic circulatory arrest (DHCA) is often avoided in patients with concomitant ascending aortic pathology when treating other cardiac disease to avoid increased risk of morbidity and mortality. We hypothesized that the use of DHCA with retrograde cerebral perfusion (RCP) does not add incremental risk to ascending aortic replacement alone in the setting of concomitant cardiac surgery. 408 ascending aortic ± hemiarch replacements and aortic (root)/mitral/tricuspid valve(s), CABG, or MAZE procedures were performed for concomitant cardiac disease. DHCA with RCP was used for all hemiarch replacements or the ascending aorta was replaced with an aortic cross-clamp proximal to the innominate artery. Propensity-score matching was used to match similar ascending patients vs. hemiarch patients; the final propensity score matched patients on age, gender, BMI, previous heart surgery, pre-op aortic insufficiency, pre-op aortic stenosis, pre-op EF, and operative variables. Propensity-score matching yielded 116 pairs of Non-hemiarch patients vs. 116 hemiarch patients. Within the propensity-score matched cohort, there were no differences in postoperative stroke (1.7% vs. 3.4%, p = 0.41), new postoperative dialysis (6.0% vs. 5.2%, p = 0.78), postoperative renal insufficiency (27.6% vs. 19.8%, p = 0.16), 30-day mortality (2.6% vs. 3.4%, p = 0.701), or 1-year mortality (4.3% vs. 4.3%, p = 1.00) CONCLUSIONS: Hemiarch replacement using DHCA with RCP does not increase the risk of operative complications compared to a normothermic, clamped-distal aortic anastomosis, and therefore its use should not be limited when planning complex multi-procedural reconstructions during elective ascending thoracic aortic replacement with concomitant cardiac surgery. Copyright © 2018. Published by Elsevier Inc.

A central role of eNOS in the protective effect of wine against metabolic syndrome.

PubMed

Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

2006-01-01

The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic

Effect of exercise training on the cardiovascular and biochemical parameters in women with eNOS gene polymorphism.

PubMed

Rezende, Tiago M; Sponton, Carlos H G; Malagrino, Pamella A; Bezerra, Marcos A C; Penteado, Carla F F; Zanesco, Angelina

2011-12-01

Presence of endothelial nitric oxide synthase (eNOS) gene polymorphism has been associated with cardiovascular disease (CVD) whereas exercise training (EX) promotes beneficial effects on CVD which is related to increased nitric oxide levels (NO). To evaluate if women with eNOS gene polymorphism at position-G894T would be less responsive to EX than those who did not carry T allele. Women were trained 3 days/week, 40 minutes session during 6 months. Cardio-biochemical parameters and genetic analysis were performed in a double-blind fashion. Plasma NOx- levels were similar in both groups at baseline (GG genotype: 18.44±3.28 μM) and (GT+TT genotype: 17.19±2.43 μM) and after EX (GG: 29.20±4.33 and GT+TT: 27.38±3.12 μM). A decrease in blood pressure was also observed in both groups. The presence of eNOS polymorphism does not affect the beneficial effects of EX in women.

Disruption of a Spermatogenic Cell-Specific Mouse Enolase 4 (Eno4) Gene Causes Sperm Structural Defects and Male Infertility1

PubMed Central

Nakamura, Noriko; Dai, Qunsheng; Williams, Jason; Goulding, Eugenia H.; Willis, William D.; Brown, Paula R.; Eddy, Edward M.

2013-01-01

ABSTRACT Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4+/Gt). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4Gt/Gt) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4Gt/Gt mice compared to wild-type mice. Sperm from Eno4Gt/Gt mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm. PMID:23446454

Activation of the AMP-Activated Protein Kinase by Eicosapentaenoic Acid (EPA, 20:5 n-3) Improves Endothelial Function In Vivo

PubMed Central

Wu, Yong; Zhang, Cheng; Dong, Yunzhou; Wang, Shuangxi; Song, Ping; Viollet, Benoit; Zou, Ming-Hui

2012-01-01

The aim of the present study was to test the hypothesis that the cardiovascular-protective effects of eicosapentaenoic acid (EPA) may be due, in part, to its ability to stimulate the AMP-activated protein kinase (AMPK)-induced endothelial nitric oxide synthase (eNOS) activation. The role of AMPK in EPA-induced eNOS phosphorylation was investigated in bovine aortic endothelial cells (BAEC), in mice deficient of either AMPKα1 or AMPKα2, in eNOS knockout (KO) mice, or in Apo-E/AMPKα1 dual KO mice. EPA-treatment of BAEC increased both AMPK-Thr172 phosphorylation and AMPK activity, which was accompanied by increased eNOS phosphorylation, NO release, and upregulation of mitochondrial uncoupling protein-2 (UCP-2). Pharmacologic or genetic inhibition of AMPK abolished EPA-enhanced NO release and eNOS phosphorylation in HUVEC. This effect of EPA was absent in the aortas isolated from either eNOS KO mice or AMPKα1 KO mice fed a high-fat, high-cholesterol (HFHC) diet. EPA via upregulation of UCP-2 activates AMPKα1 resulting in increased eNOS phosphorylation and consequent improvement of endothelial function in vivo. PMID:22532857

ENOS, ET-1 and ETB-R immunoreactivities in the porcine mesometrial lymphatics during the estrous cycle.

PubMed

Doboszyńska, Teresa; Andronowska, Aneta

2002-01-01

Abstract: Immunohistochemical localization and distribution of nitric oxide synthase (eNOS), endothelin (ET-1) and endothelin beta receptor (ETB-R) were investigated in precollector and collector lymph vessels in the broad ligament of the uterus during different phases of the estrous cycle in pigs. The polyclonal antibody for ET-1 and ETB-R and monoclonal antibody for eNOS isoform were used to perform observations on the light microscopic level. Immunoreactivities to ET-1, ETB-R and eNOS were observed in the endothelium of precollector and collector lymphangions but not in smooth muscle cells of the lymphatics examined. The staining for eNOS in the endothelial cells of all studied lymphatic vessels was stronger comparing to ET-1 and ETB-R. During the estrous cycle, only eNOS showed the correlation with the particular phases of the estrous cycle. The differences between ET-1 and ETB-R immunoreactivities were very slight and rather independent of the size or type of the lymphatic lymphangions and estrous cycle. The highest immunoreactivity level for eNOS was displayed by collector lymphangions with widened lumen in the follicular phase comparing to the precollector ones. During the luteal phase, a slight decrease in the reaction intensity was observed. The immunoreactivities for ET-1 in the endothelium of the studied vessels was not comparable with the presence or with the reactivity level of ETB-R. Optically stronger immunoreaction for ETB-R was observed in the cytoplasm of collector lymphangions in the follicular phase. eNOS, ET-1 and ETB-R were also present in the cytoplasm of the lymphatic valves. These results suggest that ET-1 and eNOS can play a role in the mechanisms regulating the vascular contractile activity, promoting lymph flow during the estrous cycle in the porcine broad ligament.

Nitric Oxide Stimulates Matrix Synthesis and Deposition by Adult Human Aortic Smooth Muscle Cells Within Three-Dimensional Cocultures

PubMed Central

Simmers, Phillip; Gishto, Arsela; Vyavahare, Narendra

2015-01-01

Vascular diseases are characterized by the over-proliferation and migration of aortic smooth muscle cells (SMCs), and degradation of extracellular matrix (ECM) within the vessel wall, leading to compromise in cell–cell and cell–matrix signaling pathways. Tissue engineering approaches to regulate SMC over-proliferation and enhance healthy ECM synthesis showed promise, but resulted in low crosslinking efficiency. Here, we report the benefits of exogenous nitric oxide (NO) cues, delivered from S-Nitrosoglutathione (GSNO), to cell proliferation and matrix deposition by adult human aortic SMCs (HA-SMCs) within three-dimensional (3D) biomimetic cocultures. A coculture platform with two adjacent, permeable 3D culture chambers was developed to enable paracrine signaling between vascular cells. HA-SMCs were cultured in these chambers within collagen hydrogels, either alone or in the presence of human aortic endothelial cells (HA-ECs) cocultures, and exogenously supplemented with varying GSNO dosages (0–100 nM) for 21 days. Results showed that EC cocultures stimulated SMC proliferation within GSNO-free cultures. With increasing GSNO concentration, HA-SMC proliferation decreased in the presence or absence of EC cocultures, while HA-EC proliferation increased. GSNO (100 nM) significantly enhanced the protein amounts synthesized by HA-SMCs, in the presence or absence of EC cocultures, while lower dosages (1–10 nM) offered marginal benefits. Multi-fold increases in the synthesis and deposition of elastin, glycosaminoglycans, hyaluronic acid, and lysyl oxidase crosslinking enzyme (LOX) were noted at higher GSNO dosages, and coculturing with ECs significantly furthered these trends. Similar increases in TIMP-1 and MMP-9 levels were noted within cocultures with increasing GSNO dosages. Such increases in matrix synthesis correlated with NO-stimulated increases in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression within EC

Flaxseed oil increases aortic reactivity to phenylephrine through reactive oxygen species and the cyclooxygenase-2 pathway in rats

PubMed Central

2014-01-01

Background Flaxseed oil has the highest concentration of omega-3 α-linolenic acid, which has been associated with cardiovascular benefit. However, the mechanism underlying the vascular effects induced through flaxseed oil is not well known. Thus, in the present study, we investigated the effects of flaxseed oil on vascular function in isolated rat aortic rings. Methods Wistar rats were treated daily with flaxseed oil or a control (mineral oil) intramuscular (i.m.) for fifteen days. Isolated aortic segments were used to evaluate cyclooxygenase-2 (COX-2) protein expression, superoxide anion levels and vascular reactivity experiments. Results Flaxseed oil treatment increased the vasoconstrictor response of aortic rings to phenylephrine. Endothelium removal increased the response to phenylephrine in aortic segments isolated from both groups, but the effect was smaller in the treated group. L-NAME incubation similarly increased the phenylephrine response in segments from both groups. The TXA2 synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the reactive oxygen species (ROS) scavenger apocynin, the superoxide anion scavengers tiron and the phospholipase A2 inhibitor dexamethasone partially reversed the flaxseed oil-induced increase in reactivity to phenylephrine. Conclusions These findings suggest that flaxseed oil treatment increased vascular reactivity to phenylephrine through an increase in ROS production and COX-2-derived TXA2 production. The results obtained in the present study provide new insight into the effects of flaxseed oil treatment (i.m.) on vascular function. PMID:24993607

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation.

PubMed

Uryash, Arkady; Wu, Heng; Bassuk, Jorge; Kurlansky, Paul; Sackner, Marvin A; Adams, Jose A

2009-06-01

Low-amplitude pulses to the vasculature increase pulsatile shear stress to the endothelium. This activates endothelial nitric oxide (NO) synthase (eNOS) to promote NO release and endothelial-dependent vasodilatation. Descent of the dicrotic notch on the arterial pulse waveform and a-to-b ratio (a/b; where a is the height of the pulse amplitude and b is the height of the dicrotic notch above the end-diastolic level) reflects vasodilator (increased a/b) and vasoconstrictor effects (decreased a/b) due to NO level change. Periodic acceleration (pG(z)) (motion of the supine body head to foot on a platform) provides systemic additional pulsatile shear stress. The purpose of this study was to determine whether or not pG(z) applied to rats produced endothelial-dependent vasodilatation and increased NO production, and whether the latter was regulated by the Akt/phosphatidylinositol 3-kinase (PI3K) pathway. Male rats were anesthetized and instrumented, and pG(z) was applied. Sodium nitroprusside, N(G)-nitro-l-arginine methyl ester (l-NAME), and wortmannin (WM; to block Akt/PI3K pathway) were administered to compare changes in a/b and mean aortic pressure. Descent of the dicrotic notch occurred within 2 s of initiating pG(z). Dose-dependent increase of a/b and decrease of mean aortic pressure took place with SNP. l-NAME produced a dose-dependent rise in mean aortic pressure and decrease of a/b, which was blunted with pG(z). In the presence of WM, pG(z) did not decrease aortic pressure or increase a/b. WM also abolished the pG(z) blunting effect on blood pressure and a/b of l-NAME-treated animals. eNOS expression was increased in aortic tissue after pG(z). This study indicates that addition of low-amplitude pulses to circulation through pG(z) produces endothelial-dependent vasodilatation due to increased NO in rats, which is mediated via activation of eNOS, in part, by the Akt/PI3K pathway.

Salt Inactivates Endothelial Nitric Oxide Synthase in Endothelial Cells12

PubMed Central

Li, Juan; White, James; Guo, Ling; Zhao, Xiaomin; Wang, Jiafu; Smart, Eric J.; Li, Xiang-An

2009-01-01

There is a 1–4 mmol/L rise in plasma sodium concentrations in individuals with high salt intake and in patients with essential hypertension. In this study, we used 3 independent assays to determine whether such a small increase in sodium concentrations per se alters endothelial nitric oxide synthase (eNOS) function and contributes to hypertension. By directly measuring NOS activity in living bovine aortic endothelial cells, we demonstrated that a 5-mmol/L increase in salt concentration (from 137 to 142 mmol/L) caused a 25% decrease in NOS activity. Importantly, the decrease in NOS activity was in a salt concentration-dependent manner. The NOS activity was decreased by 25, 45, and 70%, with the increase of 5, 10, and 20 mmol/L of NaCl, respectively. Using Chinese hamster ovary cells stably expressing eNOS, we confirmed the inhibitory effects of salt on eNOS activity. The eNOS activity was unaffected in the presence of equal milliosmol of mannitol, which excludes an osmotic effect. Using an ex vivo aortic angiogenesis assay, we demonstrated that salt attenuated the nitric oxide (NO)-dependent proliferation of endothelial cells. By directly monitoring blood pressure changes in response to salt infusion, we found that in vivo infusion of salt induced an acute increase in blood pressure in a salt concentration-dependent manner. In conclusion, our findings demonstrated that eNOS is sensitive to changes in salt concentration. A 5-mmol/L rise in salt concentration, within the range observed in essential hypertension patients or in individuals with high salt intake, could significantly suppress eNOS activity. This salt-induced reduction in NO generation in endothelial cells may contribute to the development of hypertension. PMID:19176751

Salt inactivates endothelial nitric oxide synthase in endothelial cells.

PubMed

Li, Juan; White, James; Guo, Ling; Zhao, Xiaomin; Wang, Jiafu; Smart, Eric J; Li, Xiang-An

2009-03-01

There is a 1-4 mmol/L rise in plasma sodium concentrations in individuals with high salt intake and in patients with essential hypertension. In this study, we used 3 independent assays to determine whether such a small increase in sodium concentrations per se alters endothelial nitric oxide synthase (eNOS) function and contributes to hypertension. By directly measuring NOS activity in living bovine aortic endothelial cells, we demonstrated that a 5-mmol/L increase in salt concentration (from 137 to 142 mmol/L) caused a 25% decrease in NOS activity. Importantly, the decrease in NOS activity was in a salt concentration-dependent manner. The NOS activity was decreased by 25, 45, and 70%, with the increase of 5, 10, and 20 mmol/L of NaCl, respectively. Using Chinese hamster ovary cells stably expressing eNOS, we confirmed the inhibitory effects of salt on eNOS activity. The eNOS activity was unaffected in the presence of equal milliosmol of mannitol, which excludes an osmotic effect. Using an ex vivo aortic angiogenesis assay, we demonstrated that salt attenuated the nitric oxide (NO)-dependent proliferation of endothelial cells. By directly monitoring blood pressure changes in response to salt infusion, we found that in vivo infusion of salt induced an acute increase in blood pressure in a salt concentration-dependent manner. In conclusion, our findings demonstrated that eNOS is sensitive to changes in salt concentration. A 5-mmol/L rise in salt concentration, within the range observed in essential hypertension patients or in individuals with high salt intake, could significantly suppress eNOS activity. This salt-induced reduction in NO generation in endothelial cells may contribute to the development of hypertension.

Increased interleukin-11 levels in thoracic aorta and plasma from patients with acute thoracic aortic dissection.

PubMed

Xu, Yao; Ye, Jing; Wang, Menglong; Wang, Yuan; Ji, Qingwei; Huang, Ying; Zeng, Tao; Wang, Zhen; Ye, Di; Jiang, Huimin; Liu, Jianfang; Lin, Yingzhong; Wan, Jun

2018-06-01

Interleukin (IL) 11 is closely related to tumor and hematological system diseases. Recent studies have demonstrated that IL-11 also participates in cardiovascular diseases, including ischemia-reperfusion mediated heart injury and acute myocardial infarction. This study aimed to investigate whether IL-11 is involved in acute thoracic aortic dissection (TAD). Aortic tissue samples from normal donors and acute TAD patients were collected, and the expression of IL-11 in all aortic tissue was analyzed. In addition, blood samples from patients with chest pain were collected and divided into a non-AD (NAD) group and a TAD group according to the results of computed tomography angiography of the thoracic aorta. The plasma IL-11, IL-17 and interferon (IFN) γ in all blood samples were measured. Compared with aortic tissue of normal controls, IL-11 was significantly increased in aortic tissue of acute TAD patients, especially in the torn section. The IL-11 was derived from aorta macrophages in TAD. In addition, the plasma IL-11, IL-17 and IFN-γ were significantly higher in acute TAD patients than in NAD patients, and the correlation analysis showed that IL-11 levels were positively correlated with levels of IFN-γ, IL-17, glucose, systolic blood pressure, diastolic blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that elevated IL11 in patients who may have diagnostic value of TAD, but less that D-dimer. IL-11 was increased in thoracic aorta and plasma of TAD patients and may be a promising biomarker for diagnosis in patients with TAD. Copyright © 2018. Published by Elsevier B.V.

The calcium channel blocker amlodipine promotes the unclamping of eNOS from caveolin in endothelial cells.

PubMed

Batova, Suzan; DeWever, Julie; Godfraind, Théophile; Balligand, Jean-Luc; Dessy, Chantal; Feron, Olivier

2006-08-01

in the absence of any detectable changes in intracellular calcium levels. The resulting increase in caveolin-free eNOS potentiates the NO production in response to agonists including VEGF and bradykinin. More generally, this work opens new avenues of treatment for drugs able to structurally alter signaling pathways concentrated in caveolae.

eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

PubMed

Silva, Bruno M; Barbosa, Thales C; Neves, Fabricia J; Sales, Allan K; Rocha, Natalia G; Medeiros, Renata F; Pereira, Felipe S; Garcia, Vinicius P; Cardoso, Fabiane T; Nobrega, Antonio C L

2014-12-01

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function. Copyright © 2014 Elsevier B.V. All rights reserved.

Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade.

PubMed

Kuang, Shao-Qing; Geng, Liang; Prakash, Siddharth K; Cao, Jiu-Mei; Guo, Steven; Villamizar, Carlos; Kwartler, Callie S; Peters, Andrew M; Brasier, Allan R; Milewicz, Dianna M

2013-09-01

Although hypertension is the most common risk factor for thoracic aortic diseases, it is not understood how increased pressures on the ascending aorta lead to aortic aneurysms. We investigated the role of angiotensin II type 1 receptor activation in ascending aortic remodeling in response to increased biomechanical forces using a transverse aortic constriction (TAC) mouse model. Two weeks after TAC, the increased biomechanical pressures led to ascending aortic dilatation and thickening of the medial and adventitial layers of the aorta. There was significant adventitial hyperplasia and inflammatory responses in TAC ascending aortas were accompanied by increased adventitial collagen, elevated inflammatory and proliferative markers, and increased cell density attributable to accumulation of myofibroblasts and macrophages. Treatment with losartan significantly blocked TAC-induced vascular inflammation and macrophage accumulation. However, losartan only partially prevented TAC-induced adventitial hyperplasia, collagen accumulation, and ascending aortic dilatation. Increased Tgfb2 expression and phosphorylated-Smad2 staining in the medial layer of TAC ascending aortas were effectively blocked with losartan. In contrast, the increased Tgfb1 expression and adventitial phospho-Smad2 staining were only partially attenuated by losartan. In addition, losartan significantly blocked extracellular signal-regulated kinase activation and reactive oxygen species production in the TAC ascending aorta. Inhibition of the angiotensin II type 1 receptor using losartan significantly attenuated the vascular remodeling associated with TAC but did not completely block the increased transforming growth factor-β1 expression, adventitial Smad2 signaling, and collagen accumulation. These results help to delineate the aortic transforming growth factor-β signaling that is dependent and independent of the angiotensin II type 1 receptor after TAC.

N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

PubMed

Xia, Zhengyuan; Liu, Min; Wu, Yong; Sharma, Vijay; Luo, Tao; Ouyang, Jingping; McNeill, John H

2006-11-21

The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

Aortic Valve Stenosis Increases Helical Flow and Flow Complexity: A Study of Intra-Operative Cardiac Vector Flow Imaging.

PubMed

Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse; Kjaergaard, Jesper; Jensen, Maiken Brit; Jensen, Jørgen Arendt; Nielsen, Michael Bachmann

2017-08-01

Aortic valve stenosis alters blood flow in the ascending aorta. Using intra-operative vector flow imaging on the ascending aorta, secondary helical flow during peak systole and diastole, as well as flow complexity of primary flow during systole, were investigated in patients with normal, stenotic and replaced aortic valves. Peak systolic helical flow, diastolic helical flow and flow complexity during systole differed between the groups (p < 0.0001), and correlated to peak systolic velocity (R = 0.94, 0.87 and 0.88, respectively). The study indicates that aortic valve stenosis increases helical flow and flow complexity, which are measurable with vector flow imaging. For assessment of aortic stenosis and optimization of valve surgery, vector flow imaging may be useful. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Aortic assessment of bicuspid aortic valve patients and their first-degree relatives.

PubMed

Straneo, Pablo; Parma, Gabriel; Lluberas, Natalia; Marichal, Alvaro; Soca, Gerardo; Cura, Leandro; Paganini, Juan J; Brusich, Daniel; Florio, Lucia; Dayan, Victor

2017-03-01

Background Bicuspid aortic valve patients have an increased risk of aortic dilatation. A deficit of nitric oxide synthase has been proposed as the causative factor. No correlation between flow-mediated dilation and aortic diameter has been performed in patients with bicuspid aortic valves and normal aortic diameters. Being a hereditary disease, we compared echocardiographic features and endothelial function in these patients and their first-degree relatives. Methods Comprehensive physical examinations, routine laboratory tests, transthoracic echocardiography, and measurements of endothelium-dependent and non-dependent flow-mediated vasodilatation were performed in 18 bicuspid aortic valve patients (14 type 1 and 4 type 2) and 19 of their first-degree relatives. Results The first-degree relatives were younger (36.7 ± 18.8 vs. 50.5 ± 13.9 years, p = 0.019) with higher ejection fractions (64.6% ± 1.7% vs. 58.4% ± 9.5%, p = 0.015). Aortic diameters indexed to body surface area were similar in both groups, the except the tubular aorta which was larger in bicuspid aortic valve patients (19.3 ± 2.7 vs. 17.4 ± 2.2 mm·m -2 , p = 0.033). Flow-dependent vasodilation was similar in both groups. A significant inverse correlation was found between non-flow-dependent vasodilation and aortic root diameter in patients with bicuspid aortic valve ( R = -0.57, p = 0.05). Conclusions Bicuspid aortic valve patients without aortopathy have larger ascending aortic diameters than their first-degree relatives. Endothelial function is similar in both groups, and there is no correlation with ascending aorta diameter. Nonetheless, an inverse correlation exists between non-endothelial-dependent dilation and aortic root diameter in bicuspid aortic valve patients.

Increase in coronary blood flow by intra-aortic balloon counterpulsation in a porcine model of myocardial reperfusion.

PubMed

Bonios, Michael J; Pierrakos, Charalampos N; Argiriou, Michael; Dalianis, Argirios; Terrovitis, John V; Dolou, Paraskevi; Drakos, Stavros G; Koudoumas, Dimitrios; Charitos, Christos E; Anastasiou-Nana, Maria I

2010-02-04

Studies of the IABP have reported variable effects on coronary blood flow (CBF). The purpose of the present study was to measure the changes in coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation in normal and reperfused porcine myocardium. A 30-ml IABP was placed in the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the mid-left anterior descending (LAD) coronary artery for 1 h, followed by reperfusion for 2 h. The effects of IABP support on systolic aortic pressure (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to the LAD occlusion site was measured at baseline and during reperfusion, with and without IABP counterpulsation. The IABP decreased SAP and aortic end-diastolic pressure in normal and reperfused myocardium, and maintained a peak aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%, 12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the assistance of the IABP (all p<0.05). In the normal heart, IABP counterpulsation decreased CBF, probably because of a decrease in myocardial oxygen demand from a decreased afterload. During reperfusion the IABP increased CBF, suggesting that it might effectively mitigate the no-reflow phenomenon. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Natural history of the ascending aorta after aortic valve replacement: risk factor analysis for late aortic complications after aortic valve replacement.

PubMed

Tsutsumi, Koji; Hashizume, Kenichi; Inoue, Yoshito

2016-05-01

The purpose of this study was to clarify the natural history of the ascending aorta and to identify risk factors for late ascending aortic events after first isolated aortic valve replacement (AVR). A total of 287 patients undergoing AVR were enrolled. The patients were categorized into two groups based on the diameter of the ascending aorta at the time of AVR, as determined by computed tomography: Group A (n = 233) was defined as an ascending aortic diameter <40 mm, and Group B (n = 54) was defined as an ascending aortic diameter ≥40 mm. The mean follow-up period was 7.6 years. The baseline diameter of the ascending aorta was 31.4 ± 4.8 mm in Group A and 44.7 ± 4.2 mm in Group B. These values increased to 35.9 ± 7.4 mm in Group A and 50.1 ± 7.3 mm in Group B during the follow-up period (P < 0.001). Ten patients had acute type A aortic dissection (Group A: 1 patient vs. Group B: 9 patients; P < 0.001), and three patients had enlargement of the ascending aorta to ≥55 mm in diameter (Group A: 1 patient vs. Group B: 2 patients). Multivariate analysis revealed that the baseline ascending aortic diameter was the only significant risk factor for developing late ascending aortic events (P < 0.001). AVR alone may not prevent further enlargement of the ascending aorta. An ascending aorta ≥40 mm in diameter at the time of AVR increased the risk of late ascending aortic events.

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats.

PubMed

Mendes Garrido Abregú, Facundo; Gobetto, María Natalia; Juriol, Lorena Vanesa; Caniffi, Carolina; Elesgaray, Rosana; Tomat, Analía Lorena; Arranz, Cristina

2018-06-01

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life. Copyright © 2018 Elsevier Inc. All rights reserved.

eNOS Deficiency Predisposes Podocytes to Injury in Diabetes

PubMed Central

Yuen, Darren A.; Stead, Bailey E.; Zhang, Yanling; White, Kathryn E.; Kabir, M. Golam; Thai, Kerri; Advani, Suzanne L.; Connelly, Kim A.; Takano, Tomoko; Zhu, Lei; Cox, Alison J.; Kelly, Darren J.; Gibson, Ian W.; Takahashi, Takamune; Harris, Raymond C.

2012-01-01

Endothelial nitric oxide synthase (eNOS) deficiency may contribute to the pathogenesis of diabetic nephropathy in both experimental models and humans, but the underlying mechanism is not fully understood. Here, we studied two common sequelae of endothelial dysfunction in diabetes: glomerular capillary growth and effects on neighboring podocytes. Streptozotocin-induced diabetes increased glomerular capillary volume in both C57BL/6 and eNOS−/− mice. Inhibiting the vascular endothelial growth factor receptor attenuated albuminuria in diabetic C57BL/6 mice but not in diabetic eNOS−/− mice, even though it inhibited glomerular capillary enlargement in both. In eNOS−/− mice, an acute podocytopathy and heavy albuminuria occurred as early as 2 weeks after inducing diabetes, but treatment with either captopril or losartan prevented these effects. In vitro, serum derived from diabetic eNOS−/− mice augmented actin filament rearrangement in cultured podocytes. Furthermore, conditioned medium derived from eNOS−/− glomerular endothelial cells exposed to both high glucose and angiotensin II activated podocyte RhoA. Taken together, these results suggest that the combined effects of eNOS deficiency and hyperglycemia contribute to podocyte injury, highlighting the importance of communication between endothelial cells and podocytes in diabetes. Identifying mediators of this communication may lead to the future development of therapies targeting endothelial dysfunction in albuminuric individuals with diabetes. PMID:22997257

Aortic Dissection in Turner Syndrome

PubMed Central

Bondy, Carolyn A.

2009-01-01

Purpose of review Turner syndrome (TS) is a relatively common disorder of female development with cardinal features of short stature and congenital cardiovascular defects (CHD). TS is the most common established cause of aortic dissection in young women, but has received little attention outside of pediatric literature. This review focuses on emerging knowledge of the characteristics of aortic disease in TS in comparison with Marfan-like syndromes and isolated aortic valve disease. Recent findings The incidence of aortic dissection is significantly increased in individuals with TS at all ages, highest during young adult years and in pregnancy. Pediatric patients with dissection have known CHD, but adults often have aortic valve and arch abnormalities detected only by screening cardiac MR (CMR). Thoracic aortic dilation in TS must be evaluated in relation to body surface area (BSA). Dilation is most prominent at the ascending aorta similar to the pattern seen in non-syndromic bicuspid aortic valve (BAV), is equally prevalent (20-30%) in children and adults, and does not seem to be rapidly progressive. Cardiovascular anomalies and risk for aortic dissection in TS are strongly linked to a history of fetal lymphedema, evidenced by the presence of neck webbing and shield chest. Summary Risk for acute aortic dissection is increased by more than 100-fold in young and middle-aged women with TS. Monitoring frequency and treatment modalities are decided on an individual basis until more information on outcomes becomes available. PMID:18839441

High-order ENO schemes applied to two- and three-dimensional compressible flow

NASA Technical Reports Server (NTRS)

Shu, Chi-Wang; Erlebacher, Gordon; Zang, Thomas A.; Whitaker, David; Osher, Stanley

1991-01-01

High order essentially non-oscillatory (ENO) finite difference schemes are applied to the 2-D and 3-D compressible Euler and Navier-Stokes equations. Practical issues, such as vectorization, efficiency of coding, cost comparison with other numerical methods, and accuracy degeneracy effects, are discussed. Numerical examples are provided which are representative of computational problems of current interest in transition and turbulence physics. These require both nonoscillatory shock capturing and high resolution for detailed structures in the smooth regions and demonstrate the advantage of ENO schemes.

Concomitant replacement of the dilated ascending aorta during aortic valve replacement; does it increase the perioperative morbidity and mortality risks?

PubMed

Lim, Ju Y; Jung, Sung H; Kim, Joon B; Kim, Dong K; Chung, Cheol H; Song, Hyun; Lee, Jae W; Choo, Suk J

2013-05-01

Concerns of increased surgical risks with ascending aortic replacement have led surgeons to manage post-stenotic aortic dilatation more conservatively during aortic valve replacement (AVR). The present study aimed to assess the prognostic implications and surgical risks of replacing the dilated aorta during AVR. Between January 1999 and March 2010, 134 patients who received surgery for aortic stenosis and post-stenotic dilatation (aorta size ≥40 mm) were included in the present study. AVR was performed in 92 patients (AVR group) while aortic valve and ascending aorta replacement (AVR + aorta group) were performed in 42 patients. Overall survival was compared between the two groups using Cox proportional hazard model after adjustment with inverse-probability-of-treatment weighting. The mean follow-up duration was 3.5 ± 3 years. There were no significant differences in the operative mortality and morbidity between the two groups. The late cardiac deaths were also not significantly different between the two groups (p = 1.00). In the AVR group, the ascending aortic expansion rate which was 0.18 mm/year over a mean follow-up duration of 2.3 ± 2.2 years by echocardiography showed a positive correlation with time (r = 0.3, p = 0.08). A relatively greater aortic expansion rate was identified as a risk factor for late mortality (p = 0.015, HR 1.08 (CI: 1.02 to 1.15). Concomitant replacement of the dilated ascending aorta during AVR did not increase the immediate postoperative morbidity or mortality risks and tended to exert a long-term beneficial effect on the risk of late mortality. © 2013 Wiley Periodicals, Inc.

Mangiferin alleviates hypertension induced by hyperuricemia via increasing nitric oxide releases.

PubMed

Yang, Hua; Bai, Wenwei; Gao, Lihui; Jiang, Jun; Tang, Yingxi; Niu, Yanfen; Lin, Hua; Li, Ling

2018-06-06

Mangiferin, a natural glucosyl xanthone, was confirmed to be an effective uric acid (UA)- lowering agent with dual action of inhibiting production and promoting excretion of UA. In this study, we aimed to evaluate the effect of mangiferin on alleviating hypertension induced by hyperuricemia. Mangiferin (30, 60, 120 mg/kg) was administered intragastrically to hyperuricemic rats induced by gavage with potassium oxonate (750 mg/kg). Systolic blood pressure (SBP), serum levels of UA, nitric oxide (NO), C-reactionprotein (CRP) and ONOO - were measured. The mRNA and protein levels of endothelial nitric oxide synthase (eNOS), intercellular adhesion molecule-1 (ICAM-1), CRP were also analyzed. Human umbilical vein endothelial cells (HUVECs) were used in vitro studies. Administration of mangiferin significantly decreased the serum urate level and SBP at 8 weeks and last to 12 weeks. Further more, mangiferin could increase the release of NO and decrease the level of CRP in blood. In addition, mangiferin reversed the protein expression of eNOS, CRP, ICAM-1 and ONOO - in aortic segments in hyperuricemic rats. The results in vitro were consistent with the observed results in vivo. Taken together, these data suggested that mangiferin has played an important part in alleviating hypertension induced by hyperuricemia via increasing NO secretion and improving endothelial function. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Apico-Aortic Conduit for severe aortic stenosis: Technique, applications, and systematic review

PubMed Central

Elmistekawy, Elsayed; Lapierre, Harry; Mesana, Thierry; Ruel, Marc

2010-01-01

Patients referred for aortic valve replacement are often elderly and may have increased surgical risk associated with ascending aortic calcification, left ventricular dysfunction, presence of coronary artery disease, previous surgery, and/or presence of several co-morbidities. Some of these patients may not be considered candidates for conventional surgery because of their high risk profile. While transcatheter aortic valve replacement constitutes a widely accepted alternative, some patients may not be eligible for this modality due to anatomic factors. Apico-Aortic Conduit (AAC) insertion (aortic valve bypass surgery) constitutes a possible option in those patients. Apico-Aortic Conduit is not a new technique, as it has been used for decades in both pediatric and adult populations. However, there is a resurging interest in this technique due to the expanding scope of elderly patients being considered for the treatment of aortic stenosis. Herein, we describe our surgical technique and provide a systematic review of recent publications on AAC insertion, reporting that there is continued use and several modifications of this technique, such as performing it through a small thoracotomy without the use of the cardiopulmonary bypass. PMID:23960619

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser(1177)/Thr(497) of endothelial nitric oxide synthase in diabetic mice.

PubMed

Matsumoto, Sachiko; Shimabukuro, Michio; Fukuda, Daiju; Soeki, Takeshi; Yamakawa, Ken; Masuzaki, Hiroaki; Sata, Masataka

2014-01-31

Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established. We measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Thr495 was measured using Western blotting, and the ratio of phosphorylation at Ser1177 to phosphorylation at Thr495 was used as a putative indicator of vascular eNOS activity. (1) Vascular endothelium-dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser1177/Thr495 phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil. These results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan's higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox.

Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events.

PubMed

Baudhuin, Linnea M; Kotzer, Katrina E; Lagerstedt, Susan A

2015-03-01

Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic events (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome. Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed. A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic event (n = 34) as compared with all other probands (n = 145) without a reported aortic event (79 vs. 39%; P < 0.0001), as well as Ghent criteria-positive probands (n = 54) without an aortic event (79 vs. 48%; P = 0.0039). Most probands with an early aortic event had a truncating or splicing variant (100% (n = 12) and 95% (n = 21) of patients younger than 30 and 40 years old, respectively). Aortic events occurred at a younger median age in patients with truncating/splicing variants (29 years) as compared with those with missense variants (51 years). A trend toward a higher frequency of truncating/splicing variants in patients with aortic dissection (n = 21) versus prophylactic surgery (n = 13) (85.7 vs. 69.3%; not significant) was observed. These aortic event- and age-associated findings may have important implications for the management of Marfan syndrome patients with FBN1 truncating and splicing variants.Genet Med 17 3, 177-187.

Supravalvular aortic stenosis in adult with anomalies of aortic arch vessels and aortic regurgitation

PubMed Central

Valente, Acrisio Sales; Alencar, Polyanna; Santos, Alana Neiva; Lobo, Roberto Augusto de Mesquita; de Mesquita, Fernando Antônio; Guimarães, Aloyra Guedis

2013-01-01

The supravalvular aortic stenosis is a rare congenital heart defect being very uncommon in adults. We present a case of supravalvular aortic stenosis in adult associated with anomalies of the aortic arch vessels and aortic regurgitation, which was submitted to aortic valve replacement and arterioplasty of the ascending aorta with a good postoperative course. PMID:24598962

Aortic Elongation and Stanford B Dissection: The Tübingen Aortic Pathoanatomy (TAIPAN) Project.

PubMed

Lescan, M; Veseli, K; Oikonomou, A; Walker, T; Lausberg, H; Blumenstock, G; Bamberg, F; Schlensak, C; Krüger, T

2017-08-01

Aortic elongation has not yet been considered as a potential risk factor for Stanford type B dissection (TBD). The role of both aortic elongation and dilatation in patients with TBD was evaluated. The aortic morphology of a healthy control group (n = 236) and patients with TBD (n = 96) was retrospectively examined using three dimensional computed tomography imaging. Curved multiplanar reformats were used to examine aortic diameters at defined landmarks and aortic segment lengths. Diameters at all landmarks were significantly larger in the TBD group. The greatest diameter difference (56%) was measured in dissected descending aortas (p < .001). The segment with the most considerable difference between the study groups with regard to elongation was the non-dissected aortic arch of patients with TBD (36%; p < .001). Elongation in the aortic arch was accompanied by a diameter increase of 21% (p < .001). In receiver-operating curve analysis, the area under the curve was .85 for the diameter and .86 for the length of the aortic arch. In addition to dilatation, aortic arch elongation is associated with the development of TBD. The diameter and length of the non-dissected aortic arch may be predictive for TBD and may possibly be used for risk assessment in the future. This study provides the basis for further prospective evaluation of these parameters. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells.

PubMed

Li, Huige; Xia, Ning; Brausch, Isolde; Yao, Ying; Förstermann, Ulrich

2004-09-01

Nitric oxide (NO) produced by endothelial nitric-oxide synthase (eNOS) represents an antithrombotic and anti-atherosclerotic principle in the vasculature. Hence, an enhanced expression of eNOS in response to pharmacological interventions could provide protection against cardiovascular diseases. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVECs), an artichoke leaf extract (ALE) increased the activity of the human eNOS promoter (determined by luciferase reporter gene assay). An organic subfraction from ALE was more potent in this respect than the crude extract, whereas an aqueous subfraction of ALE was without effect. ALE and the organic subfraction thereof also increased eNOS mRNA expression (measured by an RNase protection assay) and eNOS protein expression (determined by Western blot) both in EA.hy 926 cells and in native HUVECs. NO production (measured by NO-ozone chemiluminescence) was increased by both extracts. In organ chamber experiments, ex vivo incubation (18 h) of rat aortic rings with the organic subfraction of ALE enhanced the NO-mediated vasodilator response to acetylcholine, indicating that the up-regulated eNOS remained functional. Caffeoylquinic acids and flavonoids are two major groups of constituents of ALE. Interestingly, the flavonoids luteolin and cynaroside increased eNOS promoter activity and eNOS mRNA expression, whereas the caffeoylquinic acids cynarin and chlorogenic acid were without effect. Thus, in addition to the lipid-lowering and antioxidant properties of artichoke, an increase in eNOS gene transcription may also contribute to its beneficial cardiovascular profile. Artichoke flavonoids are likely to represent the active ingredients mediating eNOS up-regulation.

Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene.

PubMed

Kheirandish-Gozal, Leila; Khalyfa, Abdelnaby; Gozal, David; Bhattacharjee, Rakesh; Wang, Yang

2013-04-01

Obstructive sleep apnea (OSA) is a highly prevalent disorder that has been associated with an increased risk for cardiovascular morbidity, even in children. However, not all children with OSA manifest alterations in endothelial postocclusive hyperemia, an endothelial nitric oxide synthase (eNOS)-dependent response. Since expression of the eNOS gene is regulated by epigenetic mechanisms and OSA may cause epigenetic modifications such as DNA hypermethylation, we hypothesized that epigenetic modifications in the eNOS gene may underlie the differential vascular phenotypes in pediatric OSA. Age-, sex-, ethnicity-, and BMI-matched prepubertal children with polysomnographically confirmed OSA and either normal (OSAn) or abnormal (OSAab) postocclusive hyperemic responses, assessed as the time to attain peak reperfusion flow (Tmax) by laser Doppler flowmetry, were recruited. Blood genomic DNA was assessed for epigenetic modifications in the eNOS gene using pyrosequencing. Children with no evidence of OSA or endothelial dysfunction served as a control group. The study comprised 36 children with OSA (11 with OSAab and 25 with OSAn) and 35 children in the control group. Overall, the mean age was 7.5 ± 2.4 years, 65% were boys, and 30% were obese; mean apnea-hypopnea index was 18 ± 8.6/h of sleep for the children with OSA. Tmax was 66.7 ± 8.8 s in the OSAab group and 30.1 ± 8.3 s in the OSAn group (P < .001). Pyrosequencing of the proximal promoter region of the eNOS gene revealed no significant differences in six of the seven CpG sites. However, a CpG site located at position -171 (relative to transcription start site), approximating important transcriptional elements, displayed significantly higher methylation levels in the OSAab group as compared with the OSAn or control groups (81.5% ± 3.5%, 74.8% ± 1.4%, and 74.5% ± 1.7%, respectively; P < .001). eNOS mRNA expression levels were assessed in a separate group of children and were significantly reduced in the

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

PubMed Central

Hocher, Berthold; Haumann, Hannah; Rahnenführer, Jan; Reichetzeder, Christoph; Kalk, Philipp; Pfab, Thiemo; Tsuprykov, Oleg; Winter, Stefan; Hofmann, Ute; Li, Jian; Püschel, Gerhard P.; Lang, Florian; Schuppan, Detlef; Schwab, Matthias; Schaeffeler, Elke

2016-01-01

ABSTRACT Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood. PMID:27175980

Paradoxical low-flow aortic stenosis is defined by increased ventricular hydraulic load and reduced longitudinal strain.

PubMed

Holmes, Anthony A; Taub, Cynthia C; Garcia, Mario J; Shan, Jian; Slovut, David P

2017-02-01

Patients with paradoxical low-flow severe aortic stenosis (PLF-AS) reportedly have higher left ventricular hydraulic load and more systolic strain dysfunction than patients with normal-flow aortic stenosis. This study investigates the relationship of systolic loading and strain to PLF-AS to further define its pathophysiology. One hundred and twenty patients (age 79 ± 12 years, 37% men) with an indexed aortic valve area (AVAi) of 0.6 cm/m or less and an ejection fraction of 50% or higher were divided into two groups based on indexed stroke volume (SVi): PLF-AS, SVi ≤ 35 ml/m, N = 46; normal-flow aortic stenosis, SVi > 35 ml/m, N = 74). Valvular and arterial load were assessed using multiple measurements, and strain was assessed using speckle-tracking echocardiography. Patients with PLF-AS were found to have more valvular load (lower AVAi, P = 0.028; lower energy loss coefficient, P = 0.001), more arterial load [decreased arterial compliance and increased systemic vascular resistance (SVR), both P < 0.001] and more total hydraulic load [increased valvuloarterial impedance (Zva), P < 0.001]. Transvalvular gradients and arterial pressures were similar. Longitudinal strain was lower in PLF-AS (P < 0.001), but circumferential and rotation strains were similar. On adjusted regression, AVAi, SVR and longitudinal strain were associated with PLF-AS [odds ratio (OR) = 1.34, P = 0.043; OR = 1.31, P = 0.004; OR = 1.34, P = 0.011, respectively]. When SVR and AVAi were replaced with Zva, longitudinal strain and Zva (OR = 1.38, P = 0.015; OR = 1.33, P < 0.001 for both, respectively) were associated with PLF-AS. Increased hydraulic load, from more severe valvular stenosis and increased vascular resistance, and longitudinal strain impairment are associated with PLF-AS and their interplay is likely fundamental to its pathophysiology.

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

PubMed Central

Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc; Chetboul, Valérie; Su, Jin Bo

2012-01-01

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. PMID:22193759

eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.

PubMed

Marin-Medina, A; Brambila-Tapia, A J L; Picos-Cárdenas, V J; Gallegos-Arreola, M P; Figuera, L E

2016-10-24

Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.

Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation

PubMed Central

Spina, Roberto; Anthony, Chris; Muller, David WM

2015-01-01

Transcatheter aortic valve replacement with either the balloon-expandable Edwards SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the established therapeutic modality for severe aortic valve stenosis in patients who are not deemed suitable for surgical intervention due to excessively high operative risk. Native aortic valve regurgitation, defined as primary aortic incompetence not associated with aortic stenosis or failed valve replacement, on the other hand, is still considered a relative contraindication for transcatheter aortic valve therapies, because of the absence of annular or leaflet calcification required for secure anchoring of the transcatheter heart valve. In addition, severe aortic regurgitation often coexists with aortic root or ascending aorta dilatation, the treatment of which mandates operative intervention. For these reasons, transcatheter aortic valve replacement has been only sporadically used to treat pure aortic incompetence, typically on a compassionate basis and in surgically inoperable patients. More recently, however, transcatheter aortic valve replacement for native aortic valve regurgitation has been trialled with newer-generation heart valves, with encouraging results, and new ancillary devices have emerged that are designed to stabilize the annulus–root complex. In this paper we review the clinical context, technical characteristics and outcomes associated with transcatheter treatment of native aortic valve regurgitation. PMID:29588674

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people.

PubMed

Zago, Anderson Saranz; Park, Joon-Young; Fenty-Stewart, Nicola; Silveira, Leonardo Reis; Kokubun, Eduardo; Brown, Michael D

2010-11-01

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 ± 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 ± 1 μM) and G4 (14.2 ± 0.6 μM) and between G2 (20.1 ± 1.7 μM) and G4 (14.2 ± 0.6 μM). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 ± 1.2 μM) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Aortic root dilatation in athletic population.

PubMed

Pelliccia, Antonio; Di Paolo, Fernando M; Quattrini, Filippo M

2012-01-01

Remodeling of the aortic root may be expected to occur in athletes as a consequence of hemodynamic overload associated with exercise training; however, there are few data reporting its presence or extent. This review reports the current knowledge regarding the prevalence, upper limits, and clinical significance of aortic remodeling induced by athletic training. Several determinants impact aortic dimension in healthy, nonathletic individuals, including height, body size, age, sex, and blood pressure. Of these factors, anthropometric variables have the greatest impact. In athletes, the effect of exercise training appears to have only a modest additional influence on aortic dimension, although previous studies have produced some conflicting results. Specifically, data derived from the largest available athletic cohort suggest that the most hemodynamically intense endurance disciplines (eg, cycling and swimming) are associated with a significant but mild increase in aortic dimensions. Power disciplines, instead, (eg, weight lifting, throwing events) have only trivial, if any, impact. In contrast, selected data from a different athlete population suggest a more significant dimensional aortic remodeling in strength-trained individuals. In our experience, the 99th percentile value of aortic root diameter corresponds to 40 mm in males and 34 mm in females, which can reasonably be considered the upper limits of physiologic aortic root remodeling. However, a small proportion of apparently healthy male athletes (approximately 1%) show aortic enlargement above the upper limits, in the absence of systemic disease (ie, Marfan syndrome). Athletes presenting with aortic enlargement may demonstrate a further dimensional increase in midlife leading to clinically relevant aortic dilatation. Occasionally, dilation may be severe enough to warrant consideration for surgical treatment. Therefore, serial clinical and echocardiographic evaluations are recommended in athletes when aortic

Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation.

PubMed

Koos, Ralf; Mahnken, Andreas Horst; Dohmen, Guido; Brehmer, Kathrin; Günther, Rolf W; Autschbach, Rüdiger; Marx, Nikolaus; Hoffmann, Rainer

2011-07-15

This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). 57 patients (22 men, 81 ± 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 ± 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve® aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIEN™ prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade ≥ 3 (5055 ± 1753, n = 3) than in patients with AR grade < 3 (1723 ± 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Far-infrared radiation acutely increases nitric oxide production by increasing Ca{sup 2+} mobilization and Ca{sup 2+}/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

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

Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong

Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser{sup 1179} phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser{sup 1179} phosphorylation. •FIR increases intracellular Ca{sup 2+} levels. •Thermo-sensitive TRPV Ca{sup 2+} channels are unlikely to be involved in the FIR-mediated eNOS-Ser{sup 1179} phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity andmore » NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser{sup 1179}) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca{sup 2+} levels. Treatment with KN-93, a selective inhibitor of Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation

Distal re-entry closure with neobranching technique after thoracic endovascular aortic repair of Type B aortic dissection.

PubMed

Yamamoto, Masaki; Fukutomi, Takashi; Noguchi, Tatsuya; Orihashi, Kazumasa

2018-04-01

Retrograde false-lumen flow after thoracic endovascular aortic repair of Type B aortic dissection occurs occasionally and may have a negative impact on aortic remodelling and even prevent the decompression of the false lumen. A 67-year-old man with a Type B aortic dissection underwent thoracic endovascular aortic repair for severe compression of the true lumen and visceral malperfusion 7 weeks after the onset. Intraoperative angiography revealed proximal entry tear closure, but the false-lumen flow increased because of retrograde flow through the re-entry tear. Additional intervention including re-entry tear closure was performed with a neobranching technique with covered stent placement in the visceral artery from the aortic true lumen through the distal re-entry tear. We report a case of Type B aortic dissection and discuss the surgical techniques used.

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

PubMed

Bi, Yonghua; Chen, Hongmei; Li, Yahua; Yu, Zepeng; Han, Xinwei; Ren, Jianzhuang

2018-01-01

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity.

PubMed

Varshney, Rohan; Ali, Quaisar; Wu, Chengxiang; Sun, Zhongjie

2016-11-01

The objective of this study is to investigate whether stem cell delivery of secreted Klotho (SKL), an aging-suppressor protein, attenuates monocrotaline-induced pulmonary vascular dysfunction and remodeling. Overexpression of SKL in mesenchymal stem cells (MSCs) was achieved by transfecting MSCs with lentiviral vectors expressing SKL-green fluorescent protein (GFP). Four groups of rats were treated with monocrotaline, whereas an additional group was given saline (control). Three days later, 4 monocrotaline-treated groups received intravenous delivery of nontransfected MSCs, MSC-GFP, MSC-SKL-GFP, and PBS, respectively. Ex vivo vascular relaxing responses to acetylcholine were diminished in small pulmonary arteries (PAs) in monocrotaline-treated rats, indicating pulmonary vascular endothelial dysfunction. Interestingly, delivery of MSCs overexpressing SKL (MSC-SKL-GFP) abolished monocrotaline-induced pulmonary vascular endothelial dysfunction and PA remodeling. Monocrotaline significantly increased right ventricular systolic blood pressure, which was attenuated significantly by MSC-SKL-GFP, indicating improved PA hypertension. MSC-SKL-GFP also attenuated right ventricular hypertrophy. Nontransfected MSCs slightly, but not significantly, improved PA hypertension and pulmonary vascular endothelial dysfunction. MSC-SKL-GFP attenuated monocrotaline-induced inflammation, as evidenced by decreased macrophage infiltration around PAs. MSC-SKL-GFP increased SKL levels, which rescued the downregulation of SIRT1 (Sirtuin 1) expression and endothelial NO synthase (eNOS) phosphorylation in the lungs of monocrotaline-treated rats. In cultured endothelial cells, SKL abolished monocrotaline-induced downregulation of eNOS activity and NO levels and enhanced cell viability. Therefore, stem cell delivery of SKL is an effective therapeutic strategy for pulmonary vascular endothelial dysfunction and PA remodeling. SKL attenuates monocrotaline-induced PA remodeling and PA smooth muscle

Dispersive aortic cannulas reduce aortic wall shear stress affecting atherosclerotic plaque embolization.

PubMed

Assmann, Alexander; Gül, Fethi; Benim, Ali Cemal; Joos, Franz; Akhyari, Payam; Lichtenberg, Artur

2015-03-01

Neurologic complications during on-pump cardiovascular surgery are often induced by mobilization of atherosclerotic plaques, which is directly related to enhanced wall shear stress. In the present study, we numerically evaluated the impact of dispersive aortic cannulas on aortic blood flow characteristics, with special regard to the resulting wall shear stress profiles. An idealized numerical model of the human aorta and its branches was created and used to model straight as well as bent dispersive aortic cannulas with meshlike tips inserted in the distal ascending aorta. Standard cannulas with straight beveled or bent tips served as controls. Using a recently optimized computing method, simulations of pulsatile and nonpulsatile extracorporeal circulation were performed. Dispersive aortic cannulas reduced the maximum and average aortic wall shear stress values to approximately 50% of those with control cannulas, while the difference in local values was even larger. Moreover, under pulsatile circulation, dispersive cannulas shortened the time period during which wall shear stress values were increased. The turbulent kinetic energy was also diminished by utilizing dispersive cannulas, reducing the risk of hemolysis. In summary, dispersive aortic cannulas decrease aortic wall shear stress and turbulence during extracorporeal circulation and may therefore reduce the risk of endothelial and blood cell damage as well as that of neurologic complications caused by atherosclerotic plaque mobilization. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice

PubMed Central

2014-01-01

Background Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), has a higher affinity for and slower dissociation from AT1 receptors and shows stronger inverse agonism compared to other ARBs. Possible benefits of azilsartan in diabetic vascular dysfunction have not been established. Methods We measured vascular reactivity of aortic rings in male KKAy diabetic mice treated with vehicle, 0.005% azilsartan, or 0.005% candesartan cilexetil for 3 weeks. Expression of markers of inflammation and oxidative stress was measured using semiquantitative RT-PCR in the vascular wall, perivascular fat, and skeletal muscle. Phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and Thr495 was measured using Western blotting, and the ratio of phosphorylation at Ser1177 to phosphorylation at Thr495 was used as a putative indicator of vascular eNOS activity. Results (1) Vascular endothelium–dependent relaxation with acetylcholine in KKAy mice was improved by azilsartan treatment compared to candesartan cilexetil; (2) the ratio of Ser1177/Thr495 phosphorylation of eNOS was impaired in KKAy and was effectively restored by azilsartan; (3) anomalies in the expression levels of monocyte chemotactic protein 1 (MCP1), F4/80, NAD(P)H oxidase (Nox) 2, and Nox4 of the aortic wall and in the expression of TNFα in the perivascular fat were strongly attenuated by azilsartan compared to candesartan cilexetil. Conclusions These results provide evidence that azilsartan prevents endothelial dysfunction in diabetic mice, more potently than does candesartan cilexetil. Azilsartan’s higher affinity for and slower dissociation from AT1 receptors may underlie its efficacy in diabetic vascular dysfunction via a dual effect on uncoupled eNOS and on Nox. PMID:24485356

Histopathology of aortic complications in bicuspid aortic valve versus Marfan syndrome: relevance for therapy?

PubMed

Grewal, Nimrat; Franken, Romy; Mulder, Barbara J M; Goumans, Marie-José; Lindeman, Johannes H N; Jongbloed, Monique R M; DeRuiter, Marco C; Klautz, Robert J M; Bogers, Ad J J C; Poelmann, Robert E; Groot, Adriana C Gittenberger-de

2016-05-01

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients.

Post-translational modifications of eNOS augment nitric oxide availability and facilitates hypoxia adaptation in Ladakhi women.

PubMed

Pooja; Ghosh, Dishari; Bhargava, Kalpana; Sethy, Niroj Kumar

2018-06-09

The lower inhaled oxygen per volume at high altitude poses an intimidating challenge for humans to survive and reproduce. Indigenous populations of the Himalayas reportedly exhibit higher microcirculatory blood flow accompanied by higher orders of magnitude of nitric oxide (NO) products in lung, plasma and red blood cells as a vascular adaptation strategy for hypobaric hypoxia. The precise mechanism of such observed higher NO metabolites for hypoxia adaptation remains elusive. Studying high altitude native Ladakhi women, we observed significant higher eNOS mRNA and protein in blood/plasma as compared to lowland women. We also observed higher level of plasma l-citrulline and NOx (nitrates and nitrites) with concomitant lower levels of arginase mRNA and protein further suggesting higher eNOS activity and NO bioavailability. Interestingly, middle aged postmenopausal Ladakhi women exhibited significantly higher level of eNOS activity, NOx and cGMP as compared to age matched lowland women. Preferential phosphorylation of eNOS on stimulatory Ser1177 and Ser615 as well as dephosphorylation of inhibitory Thr495 site contributed to higher NO availability in Ladakhi women irrespective of age. We also observed higher levels of eNOS activating humoral factors like bradykinin and estrogen in both young and middle-aged Ladakhi women. These results suggest that an altered phosphorylation status, together with an enhanced expression of eNOS and potential humoral endothelial activators, are involved in enhanced activation of the eNOS-NO-cGMP pathway in Ladakhi women irrespective of age, reinforcing the hypothesis that NO metabolites play a major role in Himalayan pattern of hypoxia adaptation. Copyright © 2018 Elsevier Inc. All rights reserved.

Maximal Aortic Valve Cusp Separation and Severity of Aortic Stenosis

PubMed Central

Dilu, VP; George, Raju

2017-01-01

Introduction An integrated approach that incorporates two dimensional, M mode and Doppler echocardiographic evaluation has become the standard means for accurate quantification of severity of valvular aortic stenosis. Maximal separation of the aortic valve cusps during systole has been shown to correlate well with the severity of aortic stenosis measured by other echocardiographic parameters. Aim To study the correlation between Maximal Aortic valve Cusp Separation (MACS) and severity of aortic valve stenosis and to find cut-off values of MACS for detecting severe and mild aortic stenosis. Materials and Methods In the present prospective observational study, we have compared the accuracy of MACS distance and the aortic valve area calculated by continuity equation in 59 patients with varying degrees of aortic valve stenosis. Aortic leaflet separation in M mode was identified as the distance between the inner edges of the tips of these structures at mid systole in the parasternal long axis view. Cuspal separation was also measured in 2D echocardiography from the parasternal long axis view and the average of the two values was taken as the MACS. Patients were grouped into mild, moderate and severe aortic stenosis based on the aortic valve area calculated by continuity equation. The resultant data regarding maximal leaflet separation on cross-sectional echocardiogram was then subjected to linear regression analysis in regard to correlation with the peak transvalvular aortic gradient as well as the calculated aortic valve area. A cut-off value for each group was derived using ROC curve. Results There was a strong correlation between MACS and aortic valve area measured by continuity equation and the peak and mean transvalvular aortic gradients. Mean MACS was 6.89 mm in severe aortic stenosis, 9.97 mm in moderate aortic stenosis and 12.36 mm in mild aortic stenosis. MACS below 8.25 mm reliably predicted severe aortic stenosis, with high sensitivity, specificity and

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

PubMed

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

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

Hemin, a heme oxygenase-1 inducer, improves aortic endothelial dysfunction in insulin resistant rats.

PubMed

Chen, Yong-song; Zhu, Xu-xin; Zhao, Xiao-yun; Xing, Han-ying; Li, Yu-guang

2008-02-05

were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreactive tensometry was performed with thoracic aortic rings (TARs). Compared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine (ACh). Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-IX. The endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.

Bicuspid Aortic Valve

DTIC Science & Technology

2006-08-01

severe aortic stenosis . Figure 1F. Oblique axial cine bright blood imaging through the valve plane of the aorta, demonstrates the aortic valve to...the ascending aorta. This moderate to large jet is consistent with moderate to severe aortic stenosis . No diastolic jet to suggest aortic ...conditions. Functional impairment of the aortic valve—namely aortic stenosis and aortic regurgitation—is the most common complication (in up to 68-85% of

Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: implications for transcatheter aortic valve therapies.

PubMed

Philip, Femi; Faza, Nadine Nadar; Schoenhagen, Paul; Desai, Milind Y; Tuzcu, E Murat; Svensson, Lars G; Kapadia, Samir R

2015-08-01

Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV). We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents. Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents. © 2015 Wiley Periodicals, Inc.

Indication for percutaneous aortic valve implantation

PubMed Central

Akin, Ibrahim; Kische, Stephan; Rehders, Tim C.; Nienaber, Christoph A.; Rauchhaus, Mathias; Schneider, Henrik; Liebold, Andreas

2010-01-01

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively. PMID:22371763

Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

PubMed

Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

2017-11-15

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Aortic propagation velocity does not correlate with classical aortic stiffness parameters in healthy individuals.

PubMed

Arı, Hatem; Kahraman, Fatih; Türker, Yasin; Güler, Serdar; Baş, Hasan Aydın; Erdoğan, Doğan

2017-10-30

Aortic stiffness is an important cardiovascular risk marker, which can be determined using different noninvasive techniques. Aortic propagation velocity (APV) has recently been established as a novel echocardiographic parameter of aortic stiffness. This study aimed to investigate the association between APV and the classical echocardiography-derived aortic stiffness parameters, aortic distensibility (AD) and aortic strain (AS), in a group of otherwise healthy individuals. In total, 97 consecutive healthy subjects were recruited in this observational study. APV was measured using color M-mode echocardiography from the suprasternal window in the descending aorta. AS and AD were calculated using clinical blood pressure and the M-mode echocardiography-derived aortic diameters. Correlation analyses were performed between cardiovascular risk factors related to increased aortic stiffness (age, obesity, and blood pressure) and measured stiffness parameters (APV, AS, and AD). Correlation analyses were also performed among the measured stiffness parameters. Good correlation of age, blood pressure, and BMI with AS and AD was observed. One-on-one correlation of age, blood pressure, and BMI with APV was not observed. No correlation was observed between APV and AS (r=-0.05, p=0.6) or between APV and AD (r=-0.17, p=0.8). Although APV has been proposed as a novel and practical echocardiographic parameter of aortic stiffness, especially in patients with coronary artery disease, correlations between classical stiffness parameters (AS and AD) and APV were absent in healthy individuals at low-intermediate risk. The clinical and research applicability of APV should be further evaluated.

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

PubMed

Minich, L L; Tani, L Y; Hawkins, J A; Bartkowiak, R R; Royall, M L; Pantalos, G M

2001-04-01

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

Vocal cord paralysis after aortic surgery.

PubMed

DiLisio, Ralph P; Mazzeffi, Michael A; Bodian, Carol A; Fischer, Gregory W

2013-06-01

The purpose of this study was to investigate variables associated with vocal cord paralysis during complex aortic procedures. A retrospective review. A tertiary care center. Four hundred ninety-eight patients who underwent aortic surgery between 2002 and 2007. Two groups were studied. Group A patients had procedures only involving their aortic root and/or ascending aorta. Group B patients had procedures only involving their aortic arch and/or descending aorta. The incidence of vocal cord paralysis was higher (7.26% v 0.8%) in group B patients (p < 0.0001). Increasing the duration of cardiopulmonary bypass time was associated with an increased risk of vocal cord paralysis and death in both groups A and B (p = 0.0002 and 0.002, respectively). Additionally, within group B, descending aneurysms emerged as an independent risk factor associated with vocal cord paralysis (p = 0.03). Length of stay was statistically significantly longer among group A patients who suffered vocal cord paralysis (p = 0.017) and trended toward significance in group B patients who suffered vocal cord paralysis (p = 0.059). The association between tracheostomy and vocal cord paralysis among group A patients reached statistical significance (p = 0.007) and trended toward significance in group B patients (p = 0.057). Increasing duration of cardiopulmonary bypass time was associated with a higher risk of vocal cord paralysis in patients undergoing aortic surgery. Additionally, within group B patients, descending aortic aneurysm was an independent risk factor associated with vocal cord paralysis. Most importantly, vocal cord paralysis appeared to have an association between an increased length of stay and tracheostomy among a select group of patients undergoing aortic surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.

PubMed

Liu, Songling; Premont, Richard T; Rockey, Don C

2014-06-27

Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of intra-aortic counterpulsation on aortic wall energetics and damping: in vivo experiments.

PubMed

Fischer, Edmundo I Cabrera; Bia, Daniel; Camus, Juan M; Zócalo, Yanina; de Forteza, Eduardo; Armentano, Ricardo L

2008-01-01

Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model.

Caloric restriction improves endothelial dysfunction during vascular aging: Effects on nitric oxide synthase isoforms and oxidative stress in rat aorta.

PubMed

Zanetti, Michela; Gortan Cappellari, Gianluca; Burekovic, Ismet; Barazzoni, Rocco; Stebel, Marco; Guarnieri, Gianfranco

2010-11-01

Aging is characterized by activation of inducible over endothelial nitric oxide synthase (iNOS and eNOS), impaired antioxidant activity and increased oxidative stress, which reduces nitric oxide bioavailability and causes endothelial dysfunction. Caloric restriction (CR) blunts oxidative stress. We investigated whether CR impacts endothelial dysfunction in aging and the underlying mechanisms. Aortas from young (YC, 6 months of age) and old (OC, 24 months of age) rats ad-libitum fed and from old rats caloric-restricted for 3-weeks (OR, 26%) were investigated. Endothelium-dependent vasorelaxation was impaired in OC, associated with reduced eNOS and increased iNOS expression (P<0.05). Aortic nitrite was similar in OC and YC, but the contribution of calcium-independent NOS to total NOS activity was increased whereas that of calcium-dependent NOS was reduced (p≤0.0003). Plasma thiobarbituric acid-reactive substances (TBARS) were elevated in OC as well as aortic nitrotyrosine (P<0.05). Expression of manganese superoxide dismutase (MnSOD) and total SOD activity were impaired in OC (P<0.05 vs. YC), whereas copper-zinc (CuZn) SOD expression was similar in OC and YC. CR restored endothelial dysfunction in old rats, reduced iNOS expression, total nitrite and calcium-independent NOS activity in aorta (P<0.05) without changes in eNOS expression and calcium-dependent NOS activity. Sirtuin-1 expression did not differ among groups. Plasma TBARS and aortic nitrotyrosine were reduced (P<0.05) in OR compared with OC. In OR CuZnSOD protein and SOD activity increased (P<0.05) without changes in MnSOD expression. Short-term CR improves age-related endothelial dysfunction. Reversal of altered iNOS/eNOS ratio, reduced oxidative stress and increased SOD enzyme activity rather than enhanced NO production appear to be involved in this effect. Copyright © 2010 Elsevier Inc. All rights reserved.

Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification

PubMed Central

Castro, Juan M.; García-Espinosa, Victoria; Curcio, Santiago; Arana, Maite; Chiesa, Pedro; Giachetto, Gustavo; Zócalo, Yanina; Bia, Daniel

2016-01-01

The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5–15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID:26881081

Sex, pregnancy and aortic disease in Marfan syndrome.

PubMed

Renard, Marjolijn; Muiño-Mosquera, Laura; Manalo, Elise C; Tufa, Sara; Carlson, Eric J; Keene, Douglas R; De Backer, Julie; Sakai, Lynn Y

2017-01-01

Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown. In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17β-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts. Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17β-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells. Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.

Aortic insufficiency

MedlinePlus

... Heart valve - aortic regurgitation; Valvular disease - aortic regurgitation; AI - aortic insufficiency ... BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway.

PubMed

Hardigan, Trevor; Spitler, Kathryn; Matsumoto, Takayuki; Carrillo-Sepulveda, Maria Alicia

2015-11-01

Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

Mitral regurgitation after previous aortic valve surgery for bicuspid aortic valve insufficiency.

PubMed

Girdauskas, Evaldas; Disha, Kushtrim; Espinoza, Andres; Misfeld, Martin; Reichenspurner, Hermann; Borger, Michael A; Kuntze, Thomas

2017-06-01

Regurgitant bicuspid aortic valves (BAV) are reported to be associated with myxomatous degeneration of the anterior mitral leaflet. We examined the risk of late new-onset mitral regurgitation (MR) in patients who underwent aortic valve/aortic root surgery for BAV regurgitation and concomitant root dilatation. A total of 97 consecutive patients (47±11 years, 94% men) were identified from our institutional BAV database (N.=640) based on the following criteria: 1) BAV regurgitation; 2) aortic root diameter >40 mm; 3) no relevant mitral valve disease (i.e., MR<2+) and no simultaneous mitral intervention at the time of BAV surgery. All patients underwent isolated aortic valve replacement (AVR subgroup, N.=59) or aortic root replacement with a composite graft (i.e., for root aneurysm >50 mm) (ARR subgroup, N.=38) from 1995 through 2008. Echocardiographic follow-up (1009 patient-years) was obtained for all 96 (100%) hospital survivors. The primary endpoint was freedom from new-onset MR>2+ and redo mitral valve surgery. Nine patients (9.4%) showed new-onset MR>2+ after mean echocardiographic follow-up of 10.4±4.0 years postoperatively. Myxomatous degeneration and prolapse of the anterior mitral leaflet was found in all 9 patients, and the posterior leaflet was involved in 3 of them. Two patients (2%) in AVR subgroup underwent re-do mitral surgery. No MR>2+ occurred in ARR subgroup. Freedom from MR>2+ or mitral surgery at 15 years was significantly lower in AVR subgroup vs. ARR subgroup (i.e., 38% vs. 100%, P=0.01). The risk of new-onset MR is significantly increased in patients with BAV regurgitation and aortic root dilatation who undergo isolated AVR rather than root replacement. The mechanism by which aortic root replacement may prevent the occurrence of late MR in BAV root phenotype patients is to be determined.

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo

PubMed Central

Huk, Danielle J.; Hammond, Harriet L.; Kegechika, Hiroyuki; Lincoln, Joy

2013-01-01

Objective Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY-transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo, and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Methods and Results Using a combination of approaches, we defined CAVD pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RAR and RXR receptors. Conclusions Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of CAVD in the human population. PMID:23202364

Regional aortic distensibility and its relationship with age and aortic stenosis: a computed tomography study.

PubMed

Wong, Dennis T L; Narayan, Om; Leong, Darryl P; Bertaso, Angela G; Maia, Murilo G; Ko, Brian S H; Baillie, Timothy; Seneviratne, Sujith K; Worthley, Matthew I; Meredith, Ian T; Cameron, James D

2015-06-01

Aortic distensibility (AD) decreases with age and increased aortic stiffness is independently associated with adverse cardiovascular outcomes. The association of severe aortic stenosis (AS) with AD in different aortic regions has not been evaluated. Elderly subjects with severe AS and a cohort of patients without AS of similar age were studied. Proximal aortic cross-sectional-area changes during the cardiac cycle were determined using retrospective-ECG-gating on 128-detector row computed-tomography. Using oscillometric-brachial-blood-pressure measurements, the AD at the ascending-aorta (AA), proximal-descending-aorta (PDA) and distal-descending-aorta (DDA) was determined. Linear mixed effects modelling was used to determine the association of age and aortic stenosis on regional AD. 102 patients were evaluated: 36 AS patients (70-85 years), 24 AS patients (>85 years) and 42 patients without AS (9 patients <50 years, 20 patients between 51-70 years and 13 patients 70-85 years). When comparing patients 70-85 years, AA distensibility was significantly lower in those with AS compared to those without AS (0.9 ± 0.9 vs. 1.4 ± 1.1, P = 0.03) while there was no difference in the PDA (1.0 ± 1.1 vs. 1.0 ± 1.2, P = 0.26) and DDA (1.1 ± 1.2 vs. 1.2 ± 0.8, P = 0.97). In patients without AS, AD decreased with age in all aortic regions (P < 0.001). The AA in patients <50 years were the most distensible compared to other aortic regions. There is regional variation in aortic distensibility with aging. Patients with aortic stenosis demonstrated regional differences in aortic distensibility with lower distensibility demonstrated in the proximal ascending aorta compared to an age-matched cohort.

Smooth muscle-dependent changes in aortic wall dynamics during intra-aortic counterpulsation in an animal model of acute heart failure.

PubMed

Cabrera Fischer, Edmundo I; Bia, Daniel; Zócalo, Yanina; Armentano, Ricardo L

2009-06-01

Intra-aortic balloon pumping (IABP) may modify arterial biomechanics; however, its effects on arterial wall properties during acute cardio-depression have not yet been fully explored. This dynamical study was designed to characterize the effects of IABP on aortic wall mechanics in an in vivo animal model of acute heart failure. Aortic pressure, diameter and blood flow were measured in six anesthetized sheep with acute cardio-depression by halothane (4%), before and during IABP (1:2). Aortic characteristic impedance and aortic wall stiffness indexes were calculated. acute experimental cardio-depression resulted in a reduction in mean aortic pressure (p<0.05) and an increase in the characteristic impedance (p<0.005), incremental elastic modulus (p<0.05), stiffness index (p<0.05) and Peterson elastic modulus (p<0.05). IABP caused an increase in the cardiac output (p<0.005) and a reduction in the systemic vascular resistances (p<0.05). In addition, the aortic impedance, incremental elastic modulus, stiffness index and Peterson modulus were significantly reduced during IABP (p<0.05). Our findings show that IABP caused changes in aortic wall impedance and intrinsic wall properties, improving the arterial functional capability and the left ventricular afterload by a reduction in both. Systemic vascular resistances and aortic stiffness were also improved by means of smooth muscle-dependent mechanisms.

Trends in Aortic Valve Replacement Procedures Between 2009 and 2015: Has Transcatheter Aortic Valve Replacement Made a Difference?

PubMed

Culler, Steven D; Cohen, David J; Brown, Phillip P; Kugelmass, Aaron D; Reynolds, Matthew R; Ambrose, Karen; Schlosser, Michael L; Simon, April W; Katz, Marc R

2018-04-01

This study reports trends in volume and adverse events associated with isolated aortic valve procedures performed in Medicare beneficiaries between 2009 and 2015. This retrospective study used the annual fiscal year Medicare Provider Analysis and Review file to identify all Medicare beneficiaries undergoing an isolated aortic valve procedure. Outcome measures included three mortality rates and nine in-hospital adverse events. The final study population consisted of 233,660 hospitalizations. During the study period, Medicare beneficiaries undergoing an aortic valve procedure increased from 22,076 to 49,362, for an average annual growth rate of 14.45%. Transcatheter aortic valve replacement (TAVR) procedures per 100,000 Medicare beneficiaries grew from 10.7 in 2012 to 41.1 in 2015. Overall, in-hospital mortality rates, cumulative 30-day mortality rates, and 90-day postdischarge mortality rates declined annually during the study period. However, the 90-day mortality rate for TAVR was nearly double the rate for the tissue surgical aortic valve replacement group. Nearly 68% of Medicare beneficiaries experienced at least one in-hospital adverse event during their index hospitalization. Medicare beneficiaries undergoing TAVR had the lowest observed adverse events rates among the aortic valve procedures in 2015. The total number of Medicare beneficiaries undergoing isolated aortic valve procedures increased from 47.5 to 88.9 per 100,000 Medicare beneficiaries during the study period. Aortic valve procedures increased significantly during this study period primarily due to the increase in TAVR, with clinical outcomes improving as well. Although long-term outcomes of TAVR are still under investigation, these results are promising. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

3D echocardiographic analysis of aortic annulus for transcatheter aortic valve replacement using novel aortic valve quantification software: Comparison with computed tomography.

PubMed

Mediratta, Anuj; Addetia, Karima; Medvedofsky, Diego; Schneider, Robert J; Kruse, Eric; Shah, Atman P; Nathan, Sandeep; Paul, Jonathan D; Blair, John E; Ota, Takeyoshi; Balkhy, Husam H; Patel, Amit R; Mor-Avi, Victor; Lang, Roberto M

2017-05-01

With the increasing use of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS), computed tomography (CT) remains the standard for annulus sizing. However, 3D transesophageal echocardiography (TEE) has been an alternative in patients with contraindications to CT. We sought to (1) test the feasibility, accuracy, and reproducibility of prototype 3DTEE analysis software (Philips) for aortic annular measurements and (2) compare the new approach to the existing echocardiographic techniques. We prospectively studied 52 patients who underwent gated contrast CT, procedural 3DTEE, and TAVR. 3DTEE images were analyzed using novel semi-automated software designed for 3D measurements of the aortic root, which uses multiplanar reconstruction, similar to CT analysis. Aortic annulus measurements included area, perimeter, and diameter calculations from these measurements. The results were compared to CT-derived values. Additionally, 3D echocardiographic measurements (3D planimetry and mitral valve analysis software adapted for the aortic valve) were also compared to the CT reference values. 3DTEE image quality was sufficient in 90% of patients for aortic annulus measurements using the new software, which were in good agreement with CT (r-values: .89-.91) and small (<4%) inter-modality nonsignificant biases. Repeated measurements showed <10% measurements variability. The new 3D analysis was the more accurate and reproducible of the existing echocardiographic techniques. Novel semi-automated 3DTEE analysis software can accurately measure aortic annulus in patients with severe AS undergoing TAVR, in better agreement with CT than the existing methodology. Accordingly, intra-procedural TEE could potentially replace CT in patients where CT carries significant risk. © 2017, Wiley Periodicals, Inc.

Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment.

PubMed

Wong, Nathan D; Sciammarella, Maria; Arad, Yadon; Miranda-Peats, Romalisa; Polk, Donna; Hachamovich, Rory; Friedman, John; Hayes, Sean; Daniell, Anthony; Berman, Daniel S

2003-10-15

Aortic calcium, aortic valve calcium (AVC), and coronary artery calcium (CAC) have been associated with cardiovascular event risk. We examined the prevalence of thoracic aortic calcium (TAC) and AVC in relation to the presence and extent of CAC, cardiovascular risk factors, and estimated risk of coronary heart disease (CHD). In 2,740 persons without known CHD aged 20 to 79 years, CAC was assessed by electron beam- or multidetector-computed tomography. We determined the prevalence of TAC and AVC in relation to CAC, CHD risk factors, and predicted 10-year risk of CHD. A close correspondence of TAC and AVC was observed with CAC. TAC and AVC increased with age; by the eighth decade of life, the prevalence of TAC was similar to that of CAC (>80%), and 36% of men and 24% of women had AVC. Age, male gender, and low-density lipoprotein cholesterol were directly related to the likelihood of CAC, TAC, and AVC; higher diastolic blood pressure and cigarette smoking additionally predicted CAC. Body mass index and higher systolic and lower diastolic blood pressures were also related to TAC, and higher body mass index and lower diastolic blood pressure were related to AVC. Calculated risk of CHD increased with the presence of AVC and TAC across levels of CAC. TAC and AVC provided incremental value over CAC in association with the 10-year calculated risk of CHD. If longitudinal studies show an incremental value of aortic and aortic valve calcium over that of CAC for prediction of cardiovascular events, future guidelines for risk assessment incorporating CAC assessment may additionally incorporate the measurement of aortic and/or aortic valve calcium.

Abdominal aortic aneurysm neck remodeling after open aneurysm repair.

PubMed

Falkensammer, Juergen; Oldenburg, W Andrew; Biebl, Matthias; Hugl, Beate; Hakaim, Albert G; Crook, Julia E; Berland, Todd L; Paz-Fumagalli, Ricardo

2007-05-01

Proximal endovascular aortic graft fixation and maintenance of hemostatic seal depends on the long-term stability of the aortic neck. Previous investigations of aortic neck dilation mostly focused on the infrarenal aortic diameter. Fenestrated and branched stent grafts facilitate suprarenal graft fixation and may thereby improve the long-term integrity of the aortic attachment site. For these devices, the natural history of the suprarenal aortic segment is also of interest. We investigated the natural history of the supra- and infrarenal aortic segment after open abdominal aortic aneurysm (AAA) repair. For this retrospective analysis, we reviewed the preoperative and the initial postoperative as well as the most recent CT series that were obtained from 52 patients undergoing conventional repair of an infrarenal abdominal aortic aneurysm between January 1998 and December 2002. Measurements were performed using electronic calipers on a "split screen", allowing direct comparison of subsequent CT series at corresponding levels along the vessel. Main outcome measures were changes in postoperative measures of the supra- and infrarenal aortic diameters. The first postoperative exam was at a mean (+/-SD) of 7.0 +/- 3.5 months, and the final exams were at 44.4 +/- 21 months. Over this time period, the estimated rate of change in suprarenal diameter was 0.18 mm/ y with 95% confidence interval (CI) from 0.08 to 0.27. The estimated rate of change for the infrarenal diameter was 0.16 (95% CI: 0.05 to 0.27). A clinically relevant diameter increase of >or=3 mm was observed in seven patients (13%). There was evidence of larger diameter increases associated with larger AAA diameters (P = .003 and <.001 for suprarenal and infrarenal diameters), an inverted funnel shape (P = .002 and <.001), and marginal evidence of association with a history of inguinal hernia (P = .043 and .066). Although there is statistically significant evidence of increases in the supra- and infrarenal aortic

Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis.

PubMed

Bai, Feng; Pang, Xue-Fen; Zhang, Li-Hui; Wang, Ning-Ping; McKallip, Robert J; Garner, Ronald E; Zhao, Zhi-Qing

2016-05-15

This study tested the hypothesis that angiotensin II (Ang II) AT1 receptor is involved in development of hypertension and cardiac fibrosis via modifying ACE2 activity, eNOS expression and CD44-hyaluronan interaction. Male Sprague-Dawley rats were subjected to Ang II infusion (500ng/kg/min) using osmotic minipumps up to 4weeks and the AT1 receptor blocker, telmisartan was administered by gastric gavage (10mg/kg/day) during Ang II infusion. Our results indicated that Ang II enhances AT1 receptor, downregulates AT2 receptor, ACE2 activity and eNOS expression, and increases CD44 expression and hyaluronidase activity, an enzyme for hyaluronan degradation. Further analyses revealed that Ang II increases blood pressure and augments vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with telmisartan significantly increased ACE2 activity and eNOS expression in the intracardiac vessels and intermyocardium. These changes occurred in coincidence with decreased blood pressure. Furthermore, the locally-expressed AT1 receptor was downregulated, as evidenced by an increased ratio of the AT2 over AT1 receptor (1.4±0.4% vs. 0.4±0.1% in Ang II group, P<0.05). Along with these modulations, telmisartan inhibited membrane CD44 expression and hyaluronidase activity, decreased populations of macrophages and myofibroblasts, and reduced expression of TGFβ1 and Smads. Collagen I synthesis and tissue fibrosis were attenuated as demonstrated by the less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in development of hypertension and cardiac fibrosis. Selective activating ACE2/eNOS and inhibiting CD44/HA interaction might be considered as the therapeutic targets for attenuating Ang II induced deleterious cardiovascular effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

PubMed

Xuan, Yue; Wang, Zhongjie; Liu, Raymond; Haraldsson, Henrik; Hope, Michael D; Saloner, David A; Guccione, Julius M; Ge, Liang; Tseng, Elaine

2018-03-08

Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4-Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects.

PubMed

van Ooij, Pim; Markl, Michael; Collins, Jeremy D; Carr, James C; Rigsby, Cynthia; Bonow, Robert O; Malaisrie, S Chris; McCarthy, Patrick M; Fedak, Paul W M; Barker, Alex J

2017-09-13

Wall shear stress (WSS) is a stimulus for vessel wall remodeling. Differences in ascending aorta (AAo) hemodynamics have been reported between bicuspid aortic valve (BAV) and tricuspid aortic valve patients with aortic dilatation, but the confounding impact of aortic valve stenosis (AS) is unknown. Five hundred seventy-one subjects underwent 4-dimensional flow magnetic resonance imaging in the thoracic aorta (210 right-left BAV cusp fusions, 60 right-noncoronary BAV cusp fusions, 245 tricuspid aortic valve patients with aortic dilatation, and 56 healthy controls). There were 166 of 515 (32%) patients with AS. WSS atlases were created to quantify group-specific WSS patterns in the AAo as a function of AS severity. In BAV patients without AS, the different cusp fusion phenotypes resulted in distinct differences in eccentric WSS elevation: right-left BAV patients exhibited increased WSS by 9% to 34% ( P <0.001) at the aortic root and along the entire outer curvature of the AAo whereas right-noncoronary BAV patients showed 30% WSS increase ( P <0.001) at the distal portion of the AAo. WSS in tricuspid aortic valve patients with aortic dilatation patients with no AS was significantly reduced by 21% to 33% ( P <0.01) in 4 of 6 AAo regions. In all patient groups, mild, moderate, and severe AS resulted in a marked increase in regional WSS ( P <0.001). Moderate-to-severe AS further increased WSS magnitude and variability in the AAo. Differences between valve phenotypes were no longer apparent. AS significantly alters aortic hemodynamics and WSS independent of aortic valve phenotype and over-rides previously described flow patterns associated with BAV and tricuspid aortic valve with aortic dilatation. Severity of AS must be considered when investigating valve-mediated aortopathy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With a Trileaflet Aortic Valve and a Dilated Aorta.

PubMed

Masri, Ahmad; Kalahasti, Vidyasagar; Svensson, Lars G; Roselli, Eric E; Johnston, Douglas; Hammer, Donald; Schoenhagen, Paul; Griffin, Brian P; Desai, Milind Y

2016-11-29

In patients with a dilated proximal ascending aorta and trileaflet aortic valve, we aimed to assess (1) factors independently associated with increased long-term mortality and (2) the incremental prognostic utility of indexing aortic root to patient height. We studied consecutive patients with a dilated aortic root (≥4 cm) that underwent echocardiography and gated contrast-enhanced thoracic aortic computed tomography or magnetic resonance angiography between 2003 and 2007. A ratio of aortic root area over height was calculated (cm 2 /m) on tomography, and a cutoff of 10 cm 2 /m was chosen as abnormal, on the basis of previous reports. All-cause death was recorded. The cohort comprised 771 patients (63 years [interquartile range, 53-71], 87% men, 85% hypertension, 51% hyperlipidemia, 56% smokers). Inherited aortopathies, moderate to severe aortic regurgitation, and severe aortic stenosis were seen in 7%, 18%, and 2%, whereas 91% and 54% were on β-blockers and angiotensin-converting enzyme inhibitors, respectively. Aortic root area/height ratio was ≥10 cm 2 /m in 24%. The Society of Thoracic Surgeons score and right ventricular systolic pressure were 3.3±3 and 31±7 mm Hg, respectively. At 7.8 years (interquartile range, 6.6-8.9), 280 (36%) patients underwent aortic surgery (76% within 1 year) and 130 (17%) died (1% in-hospital postoperative mortality). A lower proportion of patients in the surgical (versus nonsurgical) group died (13% versus 19%, P<0.01). On multivariable Cox proportional hazard analysis, aortic root area/height ratio (hazard ratio, 4.04; 95% confidence interval [CI], 2.69-6.231) was associated with death, whereas aortic surgery (hazard ratio, 0.47; 95% CI, 0.27-0.81) was associated with improved survival (both P<0.01). For longer-term mortality, the addition of aortic root area/height ratio ≥10 cm 2 /m to a clinical model (Society of Thoracic Surgeons score, inherited aortopathies, hypertension, hyperlipidemia, medications, aortic

Double aortic arch

MedlinePlus

Aortic arch anomaly; Double arch; Congenital heart defect - double aortic arch; Birth defect heart - double aortic arch ... aorta is a single arch that leaves the heart and moves leftward. In double aortic arch, some ...

Associations of the eNOS G894T gene polymorphism with target organ damage in children with newly diagnosed primary hypertension.

PubMed

Śladowska-Kozłowska, Joanna; Litwin, Mieczysław; Niemirska, Anna; Wierzbicka, Aldona; Roszczynko, Marta; Szperl, Małgorzata

2015-12-01

The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism is associated with the risk of primary hypertension (PH) and vascular complications in adults with PH. We explored the associations of the G894T polymorphism with 24-h ambulatory blood pressure, left ventricular mass (LVM), carotid intima media thickness (cIMT), urinary albumin excretion, oxidative stress and inflammatory parameters in 126 children with newly diagnosed PH and in 83 healthy children. Among the 126 children with PH 92 (73%) had ambulatory hypertension and 34 (27%) had severe ambulatory hypertension. Left ventricular hypertrophy (LVH) was detected in 39 (31%) patients, cIMT of >2 standard deviation scores in 21 (16.6%) patients, albuminuria of >30 mg/24 h in 18 (14.3%) patients and metabolic syndrome (MS) in 22 (17.5%) patients. The frequency of the T allele was 52.4% in the PH group and 54.2% in the control group (not significant), and in both groups the frequency of the T allele was consistent with the Hardy-Weinberg equilibrium. Compared with G allele carriers, hypertensive T allele carriers had increased cIMT (p < 0.05) and more severe albuminuria (not significant, p = 0.1); there was no difference between the groups in hypertension severity and LVM. T and G allele distribution did not differ between patients with and without metabolic syndrome. No significant correlations between the assessed parameters and the eNOS G894T gene polymorphism were found in the controls, although T allele carriers tended to have an increased cIMT (p = 0.09). The eNOS T allele is not more prevalent among hypertensive children than among healthy ones, but it is associated with early vascular damage in children with PH, independent of metabolic abnormalities. No associations between the eNOS G894T polymorphism and metabolic abnormalities were found.

Implementation of transcatheter aortic valve replacement in California: Influence on aortic valve surgery.

PubMed

Maximus, Steven; Milliken, Jeffrey C; Danielsen, Beate; Shemin, Richard; Khan, Junaid; Carey, Joseph S

2018-04-01

Transcatheter aortic valve replacement (TAVR) procedures were introduced in 2011. Initially, procedures were limited to patients who were not surgical candidates, but subsequently high-risk surgical candidates were considered for TAVR. The influence on aortic valve surgery in California is unknown. The California Office of Statewide Health Planning and Development hospitalized patient discharge database was queried for the years 2009 through 2014. isolated surgical aortic valve and aortic valve/coronary artery bypass graft (SAVR) and TAVR procedures were identified by International Classification of Diseases-9th revision clinical modification procedure codes. Seven TAVR programs were introduced in 2011, 12 in 2012, 3 in 2013, and 6 in 2014. SAVR procedure volumes were compared from the 2 years before institution with SAVR volumes during the year(s) after institution of the TAVR program in these 28 hospitals. Overall, surgical volumes increased during the first, second, and third years after implementation of TAVR procedures. Among 7 hospitals with 4-year programs, surgical volumes increased to a maximum of 15.5% during the third year, then began to decrease. The hospital performing the largest number of TAVR procedures showed a marked decrease in SAVR volume by the fourth year, suggesting a shift of SAVR candidates to TAVR. Among all hospitals with 4-year programs, TAVR exceeded SAVR procedures by the fourth year. In California overall, SAVR increased during 2011 through 2013, due primarily to increasing volume of isolated SAVR procedures. Statewide, isolated SAVR increased from a yearly average of 3111 procedures during 2009-2010 to 3592 (+15.5%) in 2013, then decreased slightly in 2014. SAVR plus coronary artery bypass graft procedures decreased during the same time period. After implementation of TAVR, hospital SAVR volumes increased moderately, then began to decrease by the fourth year, when TAVR volume exceeded SAVR. Surgical candidates may be identified

Progression of aortic stenosis in the boxer.

PubMed

French, A; Luis Fuentes, V; Dukes-McEwan, J; Darke, P G; Martin, M; Corcoran, B

2000-10-01

Thirty-five boxers that had been referred to the Royal (Dick) School of Veterinary Studies between 1989 and 1994 with left heart base murmurs and aortic velocities greater than 1.5 m/second on Doppler echocardiography were recalled for clinical examination and Doppler echocardiography between 1995 and 1996. Five dogs (14 per cent) showed an increase in murmur grade on repeat visit. Six dogs (17 per cent) showed an increase in aortic velocity of greater than 20 per cent. Eight dogs (23 per cent) had developed aortic valvular or subvalvular two-dimensional echocardiographic changes that had not been present at the initial visit. Seven dogs (20 per cent) had developed aortic regurgitation, and three dogs (8 per cent) mitral regurgitation.

Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

PubMed Central

Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

2016-01-01

This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension.

PubMed

Hashimoto, Junichiro; Ito, Sadayoshi

2015-07-01

Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function. © 2015 American Heart Association

Variable effects of maternal and paternal-fetal contribution to the risk for preeclampsia combining GSTP1, eNOS, and LPL gene polymorphisms.

PubMed

Pappa, Kalliopi I; Roubelakis, Maria; Vlachos, George; Marinopoulos, Spyros; Zissou, Antonia; Anagnou, Nicholas P; Antsaklis, Aris

2011-04-01

To evaluate the maternal, paternal, and fetal genotype contribution to preeclampsia. STUDY DESIGN, MATERIALS, AND METHODS: We combined the analysis of polymorphisms of the GSTP1, eNOS, and LPL genes - affecting biotransformation enzymes and endothelial function - in a cohort of 167 preeclamptic and normal control trios (mother, father, and child) comprising a total of 501 samples in the Greek population, never analyzed before by this approach. For the frequency of the GSTP1 Ile(105)/Val(105), the eNOS Glu298Asp and the LPL-93 polymorphisms, statistically significant differences were found between the two groups. However, the transmission rates of the parental alleles to neonates studied by the transmission disequilibrium test, disclosed no increased rate of transmission to preeclampsia children for the variant alleles of Val(105) GSTP1, 298Asp eNOS, and -93G LPL. These novel data, suggest that interaction of all three types of genotypes (mother, father and neonate), reveals no effects on the development of preeclampsia, but provide the impetus for further studies to decipher the individual contribution of each genetic parameter of preeclampsia.

Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for Aortic Stenosis.

PubMed

Lindman, Brian R; Otto, Catherine M; Douglas, Pamela S; Hahn, Rebecca T; Elmariah, Sammy; Weissman, Neil J; Stewart, William J; Ayele, Girma M; Zhang, Feifan; Zajarias, Alan; Maniar, Hersh S; Jilaihawi, Hasan; Blackstone, Eugene; Chinnakondepalli, Khaja M; Tuzcu, E Murat; Leon, Martin B; Pibarot, Philippe

2017-07-01

After aortic valve replacement, left ventricular afterload is often characterized by the residual valve obstruction. Our objective was to determine whether higher systemic arterial afterload-as reflected in blood pressure, pulsatile and resistive load-is associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). Total, pulsatile, and resistive arterial load were measured in 2141 patients with severe aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause mortality. Lower SBP at 30 days after TAVR was associated with higher mortality (20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P <0.001). This association remained significant after adjustment, was consistent across subgroups, and confirmed in sensitivity analyses. In adjusted models that included SBP, higher total and pulsatile arterial load were associated with increased mortality ( P <0.001 for all), but resistive load was not. Patients with low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio, 3.62; 95% confidence interval, 2.36-5.55). Even after relief of valve obstruction in patients with aortic stenosis, there is an independent association between post-TAVR blood pressure, systemic arterial load, and mortality. Blood pressure goals in patients with a history of aortic stenosis may need to be redefined. Increased pulsatile arterial load, rather than blood pressure, may be a target for adjunctive medical therapy to improve outcomes after TAVR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. © 2017 American Heart Association, Inc.

Aortic valve dysfunction and aortic dilation in adults with coarctation of the aorta.

PubMed

Clair, Mathieu; Fernandes, Susan M; Khairy, Paul; Graham, Dionne A; Krieger, Eric V; Opotowsky, Alexander R; Singh, Michael N; Colan, Steven D; Meijboom, Erik J; Landzberg, Michael J

2014-01-01

To determine the prevalence of aortic valve dysfunction, aortic dilation, and aortic valve and ascending aortic intervention in adults with coarctation of the aorta (CoA). Aortic valve dysfunction and aortic dilation are rare among children and adolescents with CoA. With longer follow-up, adults may be more likely to have progressive disease. We retrospectively reviewed all adults with CoA, repaired or unrepaired, seen at our center between 2004 and 2010. Two hundred sixteen adults (56.0% male) with CoA were identified. Median age at last evaluation was 28.3 (range 18.0 to 75.3) years. Bicuspid aortic valve (BAV) was present in 65.7%. At last follow-up, 3.2% had moderate or severe aortic stenosis, and 3.7% had moderate or severe aortic regurgitation. Dilation of the aortic root or ascending aorta was present in 28.0% and 41.6% of patients, respectively. Moderate or severe aortic root or ascending aortic dilation (z-score > 4) was present in 8.2% and 13.7%, respectively. Patients with BAV were more likely to have moderate or severe ascending aortic dilation compared with those without BAV (19.5% vs. 0%; P < 0.001). Age was associated with ascending aortic dilation (P = 0.04). At most recent follow-up, 5.6% had undergone aortic valve intervention, and 3.2% had aortic root or ascending aortic replacement. In adults with CoA, significant aortic valve dysfunction and interventions during early adulthood were uncommon. However, aortic dilation was prevalent, especially of the ascending aorta, in patients with BAV. © 2013 Wiley Periodicals, Inc.

Predictive risk models for proximal aortic surgery

PubMed Central

Díaz, Rocío; Pascual, Isaac; Álvarez, Rubén; Alperi, Alberto; Rozado, Jose; Morales, Carlos; Silva, Jacobo; Morís, César

2017-01-01

Predictive risk models help improve decision making, information to our patients and quality control comparing results between surgeons and between institutions. The use of these models promotes competitiveness and led to increasingly better results. All these virtues are of utmost importance when the surgical operation entails high-risk. Although proximal aortic surgery is less frequent than other cardiac surgery operations, this procedure itself is more challenging and technically demanding than other common cardiac surgery techniques. The aim of this study is to review the current status of predictive risk models for patients who undergo proximal aortic surgery, which means aortic root replacement, supracoronary ascending aortic replacement or aortic arch surgery. PMID:28616348

Effects of different levels of exercise volume on endothelium-dependent vasodilation: roles of nitric oxide synthase and heme oxygenase.

PubMed

Sun, Meng-Wei; Zhong, Mei-Fang; Gu, Jun; Qian, Feng-Lei; Gu, Jian-Zhong; Chen, Hong

2008-04-01

The objective of this study was to examine the effects of moderate and high levels of exercise volume on endothelium-dependent vasodilation and associated changes in vascular endothelial/inducible nitric oxide synthase (eNOS and iNOS) and heme oxygenase (HO). Male Sprague-Dawley rats were assigned to sedentary control, acute (2 weeks), or chronic (6 weeks) treadmill running at moderate intensity (50% maximal aerobic velocity) with different durations of exercise episodes: 2 h/d (endurance training, moderate volume) and 3 h/d (intense training, high volume). Endothelium-dependent vascular function was examined in isolated thoracic aorta. Co-localization and contents of aortic eNOS/iNOS and HO-1/HO-2 were determined with immunofluorescence and Western blotting. Compared with sedentary controls, rats subjected to acute and chronic endurance training showed enhanced endothelium-dependent relaxation (p<0.01). Whereas acetylcholine-induced dilation was inhibited completely by NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) in sedentary controls, the dilation in the training groups was only partly blocked by L-NAME (inhibition was 98+/-3%, 79+/-6%, and 77+/-5% in sedentary control, acute, and chronic training groups, respectively, p<0.01). The remnant dilation in the training groups was further inhibited by HO inhibitor protoporphyrin IX zinc, with concomitant elevation in aortic eNOS as well as HO-1 and HO-2. In contrast to endurance exercise, high-volume intense training resulted in mild hypertension with significant impairment in endothelium-dependent vasodilation and profuse increases in aortic iNOS and eNOS (p<0.01). In conclusion, endothelium-dependent vasodilation is improved by endurance exercise but impaired by chronic intense training. Elevations of vascular eNOS and HO-1/HO-2 may contribute to enhanced vasodilation, which can be offset by intense training and elevation in vascular iNOS.

Correction of aortic insufficiency with an external adjustable prosthetic aortic ring.

PubMed

Gogbashian, Andrew; Ghanta, Ravi K; Umakanthan, Ramanan; Rangaraj, Aravind T; Laurence, Rita G; Fox, John A; Cohn, Lawrence H; Chen, Frederick Y

2007-09-01

Less invasive, valve-sparing options are needed for patients with aortic insufficiency (AI). We sought to evaluate the feasibility of reducing AI with an external adjustable aortic ring in an ovine model. To create AI, five sheep underwent patch plasty enlargement of the aortic annulus and root by placement of a 10 x 15 mm pericardial patch between the right and noncoronary cusps. An adjustable external ring composed of a nylon band was fabricated and placed around the aortic root. Aortic flow, aortic pressure, and left ventricular pressures were measured with the ring loose (off) and tightened (on). Mean regurgitant orifice area decreased by 86%, from 0.07 +/- 0.03 cm2 (ring loose, off) to 0.01 +/- 0.00 cm2 (ring tightened, on) [p < 0.01]. The regurgitant fraction decreased from 18 +/- 4% to 2 +/- 1% [p < 0.01]. The ring did not significantly affect stroke volume and aortic pressure. An ovine model of aortic root dilatation resulting in acute AI has been developed. In this model, application of an external, adjustable constricting aortic ring eliminated AI. An aortic ring may be a useful adjunct in reducing AI secondary to annular dilatation.

Some Aspects of Essentially Nonoscillatory (ENO) Formulations for the Euler Equations, Part 3

NASA Technical Reports Server (NTRS)

Chakravarthy, Sukumar R.

1990-01-01

An essentially nonoscillatory (ENO) formulation is described for hyperbolic systems of conservation laws. ENO approaches are based on smart interpolation to avoid spurious numerical oscillations. ENO schemes are a superset of Total Variation Diminishing (TVD) schemes. In the recent past, TVD formulations were used to construct shock capturing finite difference methods. At extremum points of the solution, TVD schemes automatically reduce to being first-order accurate discretizations locally, while away from extrema they can be constructed to be of higher order accuracy. The new framework helps construct essentially non-oscillatory finite difference methods without recourse to local reductions of accuracy to first order. Thus arbitrarily high orders of accuracy can be obtained. The basic general ideas of the new approach can be specialized in several ways and one specific implementation is described based on: (1) the integral form of the conservation laws; (2) reconstruction based on the primitive functions; (3) extension to multiple dimensions in a tensor product fashion; and (4) Runge-Kutta time integration. The resulting method is fourth-order accurate in time and space and is applicable to uniform Cartesian grids. The construction of such schemes for scalar equations and systems in one and two space dimensions is described along with several examples which illustrate interesting aspects of the new approach.

Injuries to the Aorta, Aortic Annulus, and Left Ventricle During Transcatheter Aortic Valve Replacement: Management and Outcomes.

PubMed

Langer, Nathaniel B; Hamid, Nadira B; Nazif, Tamim M; Khalique, Omar K; Vahl, Torsten P; White, Jonathon; Terre, Juan; Hastings, Ramin; Leung, Diana; Hahn, Rebecca T; Leon, Martin; Kodali, Susheel; George, Isaac

2017-01-01

The experience with transcatheter aortic valve replacement is increasing worldwide; however, the incidence of potentially catastrophic cardiac or aortic complications has not decreased. In most cases, significant injuries to the aorta, aortic valve annulus, and left ventricle require open surgical repair. However, the transcatheter aortic valve replacement patient presents a unique challenge as many patients are at high or prohibitive surgical risk and, therefore, an open surgical procedure may not be feasible or appropriate. Consequently, prevention of these potentially catastrophic injuries is vital, and practitioners need to understand when open surgical repair is required and when alternative management strategies can be used. The goal of this article is to provide an overview of current management and prevention strategies for major complications involving the aorta, aortic valve annulus, and left ventricle. © 2016 American Heart Association, Inc.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

PubMed

Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

2010-07-01

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

A geometric reappraisal of proximal landing zones for thoracic endovascular aortic repair according to aortic arch types.

PubMed

Marrocco-Trischitta, Massimiliano M; de Beaufort, Hector W; Secchi, Francesco; van Bakel, Theodorus M; Ranucci, Marco; van Herwaarden, Joost A; Moll, Frans L; Trimarchi, Santi

2017-06-01

This study assessed whether the additional use of the aortic arch classification in type I, II, and III may complement Ishimaru's aortic arch map and provide valuable information on the geometry and suitability of proximal landing zones for thoracic endovascular aortic repair. Anonymized thoracic computed tomography scans of healthy aortas were reviewed and stratified according to the aortic arch classification, and 20 of each type of arch were selected. Further processing allowed calculation of angulation and tortuosity of each proximal landing zone. Data were described indicating both proximal landing zone and type of arch (eg, 0/I). Angulation was severe (>60°) in 2/III and in 3/III. Comparisons among the types of arch showed an increase in proximal landing zones angulation (P < .001) and tortuosity (P = .009) depending on the type of arch. Comparisons within type of arch showed no change in angulation and tortuosity across proximal landing zones within type I arch (P = .349 and P = .409), and increases in angulation and tortuosity toward more distal proximal landing zones within type II (P = .003 and P = .043) and type III (P < .001 in both). The aortic arch classification is associated with a consistent geometric pattern of the aortic arch map, which identifies specific proximal landing zones with suboptimal angulation for stent graft deployment. Arches II and III also appear to have progressively less favorable anatomy for thoracic endovascular aortic repair compared with arch I. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

PubMed

Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

2016-12-01

Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at

MDCT evaluation of acute aortic syndrome (AAS)

PubMed Central

Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Muto, Maurizio; Molino, Antonio; Scaglione, Mariano

2016-01-01

Non-traumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life-threatening aortic pathologies with significant implications on diagnosis, therapy and management. There is a common pathway for the various manifestations of AAS that eventually leads to a breakdown of the aortic intima and media. Improvements in biology and health policy and diffusion of technology into the community resulted in an associated decrease in mortality and morbidity related to aortic therapeutic interventions. Hybrid procedures, branched and fenestrated endografts, and percutaneous aortic valves have emerged as potent and viable alternatives to traditional surgeries. In this context, current state-of-the art multidetector CT (MDCT) is actually the gold standard in the emergency setting because of its intrinsic diagnostic value. Management of acute aortic disease has changed with the increasing realization that endovascular therapies may offer distinct advantages in these situations. This article provides a summary of AAS, focusing especially on the MDCT technique, typical and atypical findings and common pitfalls of AAS, as well as recent concepts regarding the subtypes of AAS, consisting of aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer and unstable aortic aneurysm or contained aortic rupture. MDCT findings will be related to pathophysiology, timing and management options to achieve a definite and timely diagnostic and therapeutic definition. In the present article, we review the aetiology, pathophysiology, clinical presentation, outcomes and therapeutic approaches to acute aortic syndromes. PMID:27033344

Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects.

PubMed

Khatami, Mehri; Ratki, Farzaneh Morteza; Tajfar, Saba; Akrami, Fatemeh

2017-09-01

Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case-control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively). The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD. Copyright © 2017. Published by Elsevier Taiwan.

Chronic Aerobic Exercise Associated to Dietary Modification Improve Endothelial Function and eNOS Expression in High Fat Fed Hamsters

PubMed Central

Boa, Beatriz C. S.; Souza, Maria das Graças C.; Leite, Richard D.; da Silva, Simone V.; Barja-Fidalgo, Thereza Christina; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

2014-01-01

Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10−8 M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10−6 M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10−4 M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial

Investigation of gene expression and serum levels of PIN1 and eNOS with high blood pressure in patients with Alzheimer disease.

PubMed

Azimi, Mina; Nikanfar, Masoud; Khakikhatibi, Fatemeh; Rahbarghazi, Reza; Nourazarian, Seyed Manuchehr; Biray Avci, Cigir; Nourazarian, Alireza

2017-09-01

According to evidence, Alzheimer's disease is known as one of the most serious neurodegenerative diseases, for which hypertension has been observed to be a key risk factor. Therefore, this study aims to examine the relationship between the PIN1 and eNOS genes expression, as well as serum levels and hypertension in Alzheimer's disease sufferers. Blood samples were obtained from subjects who were divided into four groups: the control group, normotensive Alzheimer's patients, the Alzheimer's sufferers group with hypertension, and the healthy group with only hypertension, considering the inhibition of confounding factors. Thereafter, eNOS and PIN1 genes expression along with serum levels were studied. Based on the obtained results, a statistically significant correlation didn't exist between serum level of PIN1 and the systolic and diastolic blood pressure, between serum level of eNOS and diastolic blood pressure in the norm tension Alzheimer's disease patients, between serum levels of PIN1, eNOS and systolic blood pressure, and between serum eNOS and systolic and diastolic blood pressure in the patients with hypertension (p<0.05). According to the results obtained from this study, measuring the serum levels of eNOS and Pin1 may contribute to the prognosis, prevention, and monitoring of hypertension and also to the reduction of death rates from cardiovascular diseases in Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of acute dietary nitrate supplementation on aortic blood pressure and aortic augmentation index in young and older adults.

PubMed

Hughes, William E; Ueda, Kenichi; Treichler, David P; Casey, Darren P

2016-09-30

Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults. Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults. Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With Bicuspid Aortic Valve and a Dilated Ascending Aorta.

PubMed

Masri, Ahmad; Kalahasti, Vidyasagar; Svensson, Lars G; Alashi, Alaa; Schoenhagen, Paul; Roselli, Eric E; Johnston, Douglas R; Rodriguez, L Leonardo; Griffin, Brian P; Desai, Milind Y

2017-06-01

In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height. We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm 2 /m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6-12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20-3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26-0.80) was associated with improved survival (both P <0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio. In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death. © 2017 American Heart Association, Inc.

Aorta-atria-septum combined incision for aortic valve re-replacement

PubMed Central

Xu, Yiwei; Ye, Xiaofeng; Li, Zhaolong

2018-01-01

This case report illustrates a patient who underwent supra-annular mechanical aortic valve replacement then suffered from prosthesis dysfunction, increasing pressure gradient with aortic valve. She was successfully underwent aortic valve re-replacement, sub-annular pannus removing and aortic annulus enlargement procedures through combined cardiac incision passing through aortic root, right atrium (RA), and upper atrial septum. This incision provides optimal visual operative field and simplifies dissection. PMID:29850170

Aortic cusp extension valvuloplasty with or without tricuspidization in children and adolescents: long-term results and freedom from aortic valve replacement.

PubMed

Polimenakos, Anastasios C; Sathanandam, Shyam; Elzein, Chawki; Barth, Mary J; Higgins, Robert S D; Ilbawi, Michel N

2010-04-01

Aortic cusp extension valvuloplasty is increasingly used in the management of children and adolescents with aortic stenosis or regurgitation. The durability of this approach and the freedom from valve replacement are not well defined. A study was undertaken to investigate outcomes. From July 1987 to November 2008, 142 patients aged less than 19 years underwent aortic cusp extension valvuloplasty in the form of pericardial cusp extension and tricuspidization (when needed). Three patients with truncus arteriosus and severe truncal valve insufficiency were excluded. From the available follow-up data of 139 patients, 50 had bicuspid aortic valves, 40 had congenital aortic valve stenosis, 41 had combined congenital aortic valve stenosis/insufficiency, and 8 had other diagnoses. Median follow-up was 14.4 years (0.1-21.4). Long-term mortality and freedom from aortic valve replacement were studied. There were no early, intermediate, or late deaths. Z-values of left ventricular end-diastolic dimension, aortic annulus, aortic sinus diameter, and sinotubular junction diameter before aortic valve replacement were 4.2 +/- 3.11, 2.3 +/- 1.25, 4.4 +/- 1.23, and 1.84 +/- 1.28, respectively. During the follow-up period, 64 patients underwent aortic valve reinterventions. The Ross procedure was performed in 32 of 139 patients (23%) undergoing aortic cusp extension valvuloplasty. Other aortic valve replacements were undertaken after 16 aortic cusp extension valvuloplasties (11.5%). Freedom from a second aortic cusp extension valvuloplasty or aortic valve replacement at 18 years was 82.1% +/- 4.2% and 60.0% +/- 7.2%, respectively. Aortic cusp extension valvuloplasty is a safe and effective surgical option with excellent survival and good long-term outcomes in children and adolescents. The procedure provides acceptable durability and satisfactory freedom from aortic valve replacement. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights

Chronic resveratrol enhances endothelium-dependent relaxation but does not alter eNOS levels in aorta of spontaneously hypertensive rats.

PubMed

Rush, James W E; Quadrilatero, Joe; Levy, Andrew S; Ford, Rebecca J

2007-06-01

Spontaneously hypertensive rats (SHRs) were administered the red wine polyphenol resveratrol in drinking water at 0, 0.448, or 4.48 mg/l (control, low, or high, respectively) for 28 days. The low dosage was chosen to mimic moderate red wine consumption. After the treatment period, thoracic aorta rings were excised for in vitro assessment of vasomotor function. Chronic resveratrol significantly improved endothelium-dependent relaxation to acetylcholine (Ach), increasing maximal values to 80.8% +/- 5.2% and 80.8% +/- 5.0% in low and high groups, respectively, compared with 60.7% +/- 1.4% in controls (P<0.01). This treatment effect was eliminated in the presence of the endothelial nitric oxide synthase (eNOS) blocker N(omega)-nitro-L-arginine methyl ester. Resveratrol did not affect relaxation to sodium nitroprusside or systolic blood pressure in SHRs. In contrast to the SHR results, chronic resveratrol in Sprague Dawley rats did not affect vasomotor function in aorta rings in response to Ach. Hydrogen peroxide was reduced in the SHR thoracic aorta by a high dosage of resveratrol (P<0.05), but it was not significantly altered in other tissues tested. Thoracic aorta immunoblots revealed no significant treatment effects in SHRs on eNOS, superoxide dismutases 1 and 2, gp91phox, or Hsp90. Thus, these data provide novel evidence of improved endothelium-dependent vasorelaxation in hypertensive, but not normotensive, animals as a result of chronic resveratrol consumption mimicking dosages resulting from moderate red wine consumption. This response was not dependent on increases in eNOS expression but was dependent on improved NO bioavailability.

[Application and analysis of abdominal aortic branch malperfusion pattern in thoracic endovascular aortic repair for Stanford B aortic dissection].

PubMed

Han, X F; Guo, X; Li, T Z; Liu, G R; Huang, L J

2017-12-18

To evaluate the efficiency of thoracic endovascular aortic repair (TEVAR) in dealing with abdominal aortic branch malperfusion based on the analysis of aortic computed tomography angiography (CTA) images in pre- and post-TEVAR. Retrospective analysis from September 2015 to March 2016 in single institution to 32 patients, diagnosed as Stanford B aortic dissection with abdominal aortic branch malperfusion, CTA images in pre- and post-TEVAR were collected. Based on the aortic branch malperfusion pattern redefined by Nagamine, we identified and characterized branch malperfusion pattern for four abdominal aortic branches (celiac trunk, superior mesenteric artery, bilateral renal artery) in statistical analysis. In the four abdominal aortic branches (total 128 branches), 86 branches (67.2%) expressed with Class I patterns, in which subtype I-b presented with 0.8%, subtype I-c with 5.5%; 14 branches (10.9%) expressed with Class II patterns, in which subtype II-b-1 with 3.9%, subtype II-b-2 with 3.1%; 16 branches (12.5%) expressed with Class III patterns, all with subtype III-a, no subtype III-b and III-c presented. The remaining 12 branches were normal. The 100% successful rate of TEVAR obtained in 32 patients performed. The mean following-up was 4 months. Aortic CTA showed that among the 14 "high-risk" abdominal aortic branch malperfusion, 13 (92.9%) with obvious branch malperfusion in post-TEVAR were observed to improve, and the remaining one branch malperfusion (7.1%) was observed to change from subtype I-b to I-c. Few ratios in abdominal aortic branches suffered with obvious malperfusion complicated by Stanford B aortic dissection. For branches with "high-risk" malperfusion pattern, optimal changes were observed in abdominal aortic branch without revascularization in post-TEVAR, as well other branches with non-"high-risk" pattern perfusion were mostly stable in post-TEVAR. It could be of profound benefit to extend branch malperfusion patterns redefined by Nagamine in

A novel approach: trans-ascending aorta balloon aortic valvuloplasty via sternotomy for treating severe valvular aortic stenosis in a low-weight infant.

PubMed

Gao, Lei; Wu, Qin; Xu, Xinhua; Zhao, Tianli; Jin, Wancun; Yang, Yifeng

2014-02-01

Severe congenital aortic stenosis in infants is a life-threatening congenital heart anomaly that is typically treated using percutaneous balloon aortic valvuloplasty. The usual route is the femoral artery under radiographic guidance. However, this procedure may be limited by the small size of the femoral artery in low-weight infants. An infant weighing only 7 kg with severe aortic stenosis (peak gradient was 103 mmHg) was successfully treated with a novel approach, that is trans-ascending aorta balloon aortic valvuloplasty guided by transesophageal echocardiography. The patient tolerated the procedure well, and no major complications developed. After the intervention, transesophageal echocardiography indicated a significant reduction of the aortic valvular peak gradient from 103 mmHg to 22 mmHg, no aortic regurgitation was found. Eighteen months after the intervention, echocardiography revealed that the aortic valvular peak gradient had increased to 38 mmHg and that still no aortic regurgitation had occurred. In our limited experience, trans-ascending aorta balloon aortic valvuloplasty for severe aortic stenosis under transesophageal echocardiography guidance effectively reduces the aortic peak gradient. As this is a new procedure, long-term follow up and management will need to be established. It may be an alternative technique to treat congenital aortic stenosis in low-weight patients.

Echocardiographic evaluation of aortic atheromas in patients with aortic stenosis.

PubMed

Vizzardi, Enrico; D'Aloia, Antonio; Sciatti, Edoardo; Bonadei, Ivano; Gelsomino, Sandro; Lorusso, Roberto; Metra, Marco

2015-01-01

The association of aortic atheromas in patients with isolated aortic stenosis has recently been acknowledged, probably because the pathogenic mechanisms are similar. Therefore, this study evaluated the extent and severity of thoracic aortic atheromas in patients with different grades of aortic stenosis using transesophageal echocardiography. We retrospectively evaluated transesophageal echocardiographic examinations of 686 consecutive patients with a diagnosis of aortic stenosis. The prevalence and morphologic characteristics of atheromas in 3 segments of the thoracic aorta were assessed. Plaque thickness was measured at each segment, and the thickest plaque was used to establish severity. Atheromas were graded as mild, moderate, or severe according to plaque thickness (<2, 2-4, or >4 mm, respectively). Aortic stenosis was graded as mild, moderate, or severe on the basis of the gradient and anatomic aortic valve area (>1.5, 1.0-1.5, or <1.0 cm(2)). A total of 382 patients were men, and 304 were women (mean age ± SD, 74 ± 15 years); 86% of the patients had aortic atheromas. The severe stenosis group had a significantly higher rate of atheromas (95% versus 40%; P < .001) than the mild stenosis group, with more complex atheromas (52% versus 22%; P< .001). There was no significant difference in the atheroma grades between the severe and moderate stenosis groups, but moderate cases had more moderate and severe atheromas than mild cases (45% and 15% versus 19% and 3%; P < .01). This study showed a correlation in the extent of aortic atheromas across several degrees of aortic stenosis. Patients with moderate and severe stenosis had more extensive atherosclerotic atheromas than those with mild stenosis. © 2015 by the American Institute of Ultrasound in Medicine.

Treatment strategy for ruptured abdominal aortic aneurysms.

PubMed

Davidovic, L

2014-07-01

Rupture is the most serious and lethal complication of the abdominal aortic aneurysm. Despite all improvements during the past 50 years, ruptured abdominal aortic aneurysms are still associated with very high mortality. Namely, including patients who die before reaching the hospital, the mortality rate due to abdominal aortic aneurysm rupture is 90%. On the other hand, during the last twenty years, the number of abdominal aortic aneurysms significantly increased. One of the reasons is the fact that in majority of countries the general population is older nowadays. Due to this, the number of degenerative AAA is increasing. This is also the case for patients with abdominal aortic aneurysm rupture. Age must not be the reason of a treatment refusal. Optimal therapeutic option ought to be found. The following article is based on literature analysis including current guidelines but also on my Clinics significant experience. Furthermore, this article show cases options for vascular medicine in undeveloped countries that can not apply endovascular procedures at a sufficient level and to a sufficient extent. At this moment the following is evident. Thirty-day-mortality after repair of ruptured abdominal aortic aneurysms is significantly lower in high-volume hospitals. Due to different reasons all ruptured abdominal aortic aneurysms are not suitable for EVAR. Open repair of ruptured abdominal aortic aneurysm should be performed by experienced open vascular surgeons. This could also be said for the treatment of endovascular complications that require open surgical conversion. There is no ideal procedure for the treatment of AAA. Each has its own advantages and disadvantages, its own limits and complications, as well as indications and contraindications. Future reductions in mortality of ruptured abdominal aortic aneurysms will depend on implementation of population-based screening; on strategies to prevent postoperative organ injury and also on new medical technology

Molecular and cellular mechanisms of aortic stenosis.

PubMed

Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Association of Low-Density Lipoprotein Cholesterol–Related Genetic Variants With Aortic Valve Calcium and Incident Aortic Stenosis

PubMed Central

Smith, J. Gustav; Luk, Kevin; Schulz, Christina-Alexandra; Engert, James C.; Do, Ron; Hindy, George; Rukh, Gull; Dufresne, Line; Almgren, Peter; Owens, David S.; Harris, Tamara B.; Peloso, Gina M.; Kerr, Kathleen F.; Wong, Quenna; Smith, Albert V.; Budoff, Matthew J.; Rotter, Jerome I.; Cupples, L. Adrienne; Rich, Stephen; Kathiresan, Sekar; Orho-Melander, Marju; Gudnason, Vilmundur; O’Donnell, Christopher J.; Post, Wendy S.; Thanassoulis, George

2014-01-01

aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P = .03) and aortic stenosis (P = .009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02). CONCLUSIONS AND RELEVANCE Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation. PMID:25344734

Long-term high-fat consumption leads to downregulation of Akt phosphorylation of eNOS at Ser1177 and upregulation of Sirtuin-1 expression in rat cavernous tissue.

PubMed

Tomada, I; Negrão, R; Almeida, H; Neves, D

2014-04-01

Long-term consumption of high-fat diets negatively interferes with metabolic status and promotes endothelial dysfunction and inflammation. In the cavernous tissue, these outcomes become conspicuous in the elderly and strongly affect penile erection, a vascular process highly dependent on local nitric oxide bioavailability. Although epidemiological data links erectile dysfunction to nutritional patterns, the underlying molecular mechanisms remain unclear. Therefore, we investigated the effects of long-term high-fat diet on endothelial nitric oxide synthase (eNOS)-Sirtuin-1 axis and Akt/eNOS phosphorylation in the cavernous tissue of Sprague-Dawley rats, and compared with energy-restricted animals. We demonstrated that high-fat diet intake led to a noteworthy decrease in eNOS phosphorylation at Ser1177 residue through the Akt pathway, which seems to be compensated by upregulation of phosphorylation at Ser615, but without an increment in nitric oxide production. These results are accompanied by an increase of systemic inflammatory markers and upregulation of the inducible NOS and of the deacetylase Sirtuin-1 in the cavernous tissue to levels apparently detrimental to cells and to metabolic homeostasis. Conversely, in long-term energy-restricted animals, the rate of phosphorylation of eNOS at Ser1177 diminished, but the activation of the enzyme increased through phosphorylation of eNOS at Ser615, resulting in an enhancement in nitric oxide bioavailability. Taken together, our results demonstrate that long-term nutritional conditions override the influence of age on the eNOS expression and activation in rat cavernous tissue.

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis

PubMed Central

Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana

2017-01-01

Objective Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). Methods AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. Results More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: NCT00092677 PMID:28698175

INCREASED OXIDATIVE STRESS AND DOWN REGULATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS) IN THE KIDNEY ATTEN- UATE THE RESPONSIVENESS OF (XlB ADRENERGIC RECEPTORS IN THE KIDNEY OF RATS WITH LEFT VENTRICULAR HYPERTROPHY.

PubMed

Ahmad, Ashfaq; Sattar, Munavvar; Khan, Safia Akhtar; Abdullah, Nor A; Johns, Edward J; Afzal, Samina

2017-03-01

Present study explored endothelial nitric oxide synthase/nitric oxide (eNOS/NO) pathway in the kidney and role of αIB adrenergic receptor in the regulation of renal vasculature in the rats with left ventricular hypertrophy (LVH). LVH was induced by administering isoprenaline 5 mg/kg (s.c. 72 h. apart) and caffeine (62 mg/L in drinking water) for 14 days. Quantification of molecular expression of eNOS in kidney was performed by quantitative Real Time Polymerase Chain Reaction (qPCR). Renal vasoconstrictor responses were measured by administering noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in pre-drug phase, low dose and high dose phases of chloroethylelonidine (CEC), a selective of (αIB adrenergic receptor antagonist. In the kidney of LVH male Wistar Kyoto (WKY) rats eNOS was significantly down regulated (p < 0.05) by 74% relative to Control WKY (taken as 100%). The high dose 5 CEC attenuated the vasoconstrictor responses to NA by 41%, PE by 43% and ME by 33% in the LVH-WKY when compared to the same dose phase in Control WKY group. In LVH, increased oxidative stress in kidney and increased ACE activity in the plasma resulted in down regulation of eNOS/NO in the kidney. The renal vasoconstrictor responses to adrenergic agonist are blunted in LVH and (αIB adrenergic receptor is functional subtype in renal vasculature in LVH.

Aortic valve replacement for aortic stenosis caused by alkaptonuria.

PubMed

Hiroyoshi, Junko; Saito, Aya; Panthee, Nirmal; Imai, Yasushi; Kawashima, Dai; Motomura, Noboru; Ono, Minoru

2013-03-01

We report a case of aortic stenosis associated with ochronosis in a 70-year-old man who underwent biologic aortic valve replacement. Intraoperative findings included ochronosis of a severely calcified pigmented aortic valve along with pigmentation of the intima of the aorta. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ascending aortic curvature as an independent risk factor for type A dissection, and ascending aortic aneurysm formation: a mathematical model.

PubMed

Poullis, Michael P; Warwick, Richard; Oo, Aung; Poole, Robert J

2008-06-01

To develop a mathematical model to demonstrate that ascending aortic curvature is an independent risk factor for type A dissections, in addition to hypertension, bicuspid aortic valve, aneurysm of ascending aorta, and intrinsic aortic tissue abnormalities, like Marfan's syndrome. A steady state one-dimensional flow analysis was performed, utilising Newton's third law of motion. Five different clinical scenarios were evaluated: (1) effect of aortic curvature; (2) effect of beta-blockers, (3) effect of patient size, (4) forces on a Marfan's aorta, and (5) site of entry flap in aortic dissection. Aortic curvature increases the forces exerted on the ascending aorta by a factor of over 10-fold. Aortic curvature can cause patients with a systolic blood pressure of 8 0mmHg to have greater forces exerted on their aorta despite smaller diameters and lower cardiac outputs, than patients with systolic blood pressures of 120 mmHg. In normal diameter aortas, beta-blockers have minimal effect compared with aortic curvature. Aortic curvature may help to explain why normal diameter aortas can dissect, and also that the point of the entry tear may be potentially predictable. Aortic curvature has major effects on the forces exerted on the aorta in patients with Marfan's syndrome. Aortic curvature is relatively more important that aortic diameter, blood pressure, cardiac output, beta-blocker use, and patient size with regard to the force acting on the aortic wall. This may explain why some patients with normal diameter ascending aortas with or without Marfan's syndrome develop type A dissections and aneurysms. Aortic curvature may also help to explain the site of entry tear in acute type A dissection. Further clinical study is needed to validate this study's finding.

Increased Neuron Specific Enolase Expression by Urothelial Cells Exposed to or Malignantly Transformed by Exposure to Cd+2 or As+3

PubMed Central

Soh, Maureen; Dunlevy, Jane R.; Garrett, Scott H.; Allen, Christina; Sens, Donald A.; Zhou, Xu Dong; Sens, Mary Ann; Somji, Seema

2012-01-01

Neuron specific enolase (ENO2, γ-enolase) is a biomarker used to help identify neuroendocrine differentiation in tumors. This laboratory has shown that ENO2 might be a biomarker for exposure to cadmium and arsenite. In this study these observations are extended to the urothelial cell, where environmental exposures are strongly linked to urothelial cancer. The UROtsa urothelial cell line and its Cd+2- and As+3-transformed counterparts were used as the model. Acute exposure of the UROtsa cells to both As+3- and Cd+2-caused significant increases in ENO2 expression. Treatment with the histone deacetlyase inhibitor was also shown to significantly increase the expression of ENO2 mRNA. The expression of ENO2 was significantly elevated in the Cd+2- and As+3-transformed UROtsa cells and tumor transplants. In contrast, ENO1, was unaffected by exposure to As+3 or Cd+2. Immunofluorescence showed ENO2 associated with both the nucleus and cytoplasm and cytoplasmic ENO2 co-localized with ENO1. The findings extend the evidence suggesting a link between As+3 and Cd+2 exposure and neuroendocrine differentiation in tumors. The results suggest that ENO2 might be a biomarker of human exposure to Cd+2 and As+3 that operates through histone modification. PMID:22613180

Valve-sparing aortic root replacement in bicuspid aortic valves: a reasonable option?

PubMed

Aicher, Diana; Langer, Frank; Kissinger, Anke; Lausberg, Henning; Fries, Roland; Schäfers, Hans-Joachim

2004-11-01

Aortic dilatation occurs in many patients with bicuspid aortic valves. We have added root replacement using the remodeling technique originally designed for tricuspid aortic valves to bicuspid aortic valve repair for treatment of the dilated root. We compared the results of remodeling in bicuspid aortic valves with those in tricuspid aortic valves. From October 1995 through January 2004, 60 patients underwent root remodeling for bicuspid aortic valves (group A), and 130 patients underwent root remodeling for tricuspid aortic valves (group B). Correction of cusp prolapse was more often performed in group A (group A, 50/60; group B, 47/130; P < .0001). Transthoracic echocardiography was performed at 1 week, 6 and 12 months, and every year thereafter. Cumulative follow-up was 527 patient-years (mean, 2.9 +/- 2 years). No patient died in group A. Hospital mortality in group B was 5% (5/100; 95% confidence interval,1.6%-11.3%) after elective operations and 10% (3/30; 95% confidence interval, 2.1%-26.5%) after emergency operations. Mean systolic gradients were identical at 1 year (group A, 4.8 +/- 2.1 mm Hg; group B, 4.0 +/- 2 mm Hg) and 5 years (group A, 4.5 +/- 2.3 mm Hg; group B, 3.9 +/- 2.2 mm Hg). Freedom from aortic regurgitation of grade 2 or higher at 5 years was 96% in group A and 83% in group B ( P = .07), and freedom from reoperation at 5 years was 98% in group A and 98% in group B ( P = .73). Valve-sparing aortic replacement with root remodeling can be applied to aortic dilatation and a regurgitant bicuspid aortic valve. Hemodynamic function and valve stability of a repaired bicuspid aortic valve are comparable with those seen in cases of tricuspid anatomy.

Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.

PubMed

Toussaint, Jimmy; Raval, Chirag Bharavi; Nguyen, Tieuvi; Fadaifard, Hadi; Joshi, Shripad; Wolberg, George; Quarfordt, Steven; Jan, Kung-Ming; Rumschitzki, David S

2017-11-01

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop. Copyright © 2017 the American Physiological Society.

Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery.

PubMed

Singh, S D; Xu, X Y; Pepper, J R; Izgi, C; Treasure, T; Mohiaddin, R H

2016-07-05

Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient-specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero-displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcatheter aortic-valve replacement with a self-expanding prosthesis.

PubMed

Adams, David H; Popma, Jeffrey J; Reardon, Michael J; Yakubov, Steven J; Coselli, Joseph S; Deeb, G Michael; Gleason, Thomas G; Buchbinder, Maurice; Hermiller, James; Kleiman, Neal S; Chetcuti, Stan; Heiser, John; Merhi, William; Zorn, George; Tadros, Peter; Robinson, Newell; Petrossian, George; Hughes, G Chad; Harrison, J Kevin; Conte, John; Maini, Brijeshwar; Mumtaz, Mubashir; Chenoweth, Sharla; Oh, Jae K

2014-05-08

We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).

Ascending aorta dilatation in patients with bicuspid aortic valve stenosis: a prospective CMR study.

PubMed

Rossi, Alexia; van der Linde, Denise; Yap, Sing Chien; Lapinskas, Thomas; Kirschbaum, Sharon; Springeling, Tirza; Witsenburg, Maarten; Cuypers, Judith; Moelker, Adriaan; Krestin, Gabriel P; van Dijk, Arie; Johnson, Mark; van Geuns, Robert-Jan; Roos-Hesselink, Jolien W

2013-03-01

The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV). Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up. Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R (2) = 0.16, P = 0.040). BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS.

Tracheal Compression Caused by a Mediastinal Hematoma After Interrupted Aortic Arch Surgery.

PubMed

Hua, Qingwang; Lin, Zhiyong; Hu, Xingti; Zhao, Qifeng

2017-08-03

Congenital abnormalities of the aortic arch include interrupted aortic arch (IAA), coarctation of the aorta (CoA), and double aortic arch (DAA). Aortic arch repair is difficult and postoperative complications are common. However, postoperative tracheobronchial stenosis with respiratory insufficiency is an uncommon complication and is usually caused by increased aortic anastomotic tension. We report here a case of tracheal compression by a mediastinal hematoma following IAA surgery. The patient underwent a repeat operation to remove the hematoma and was successfully weaned off the ventilator.In cases of tracheobronchial stenosis after aortic arch surgery, airway compression by increased aortic anastomotic tension is usually the first diagnosis considered by clinicians. Other causes, such as mediastinal hematomas, are often ignored. However, the severity of symptoms with mediastinal hematomas makes this an important entity.

Intra-aortic balloon pumping in acute mitral regurgitation reduces aortic impedance and regurgitant fraction.

PubMed

Dekker, André L A J; Reesink, Koen D; van der Veen, Frederik H; van Ommen, G Vincent A; Geskes, Gijs G; Soemers, A Cecilia M; Maessen, Jos G

2003-04-01

Acute mitral regurgitation (MR) is present in 10% of patients presenting with cardiogenic shock. To stabilize these patients, intra-aortic balloon pumping (IABP) is recommended, but the mechanism of IABP support in these patients is unknown. This animal study was designed to describe the hemodynamic effect of intra-aortic balloon pumping during cardiogenic shock induced by acute MR. In eight calves, left ventricular pressure-volume loops, aortic and left atrial pressure, and aortic, carotid artery, and coronary blood flow were recorded. Acute MR (range 36%-79%) was created by placing a metal cage in the mitral valve. Hemodynamic data was obtained at control, during acute MR, and during acute MR with 1:1 IABP support. Acute MR caused a decrease in cardiac output (-32%, P = 0.018), blood pressure, and carotid artery flow, whereas left ventricular output (+127%, P = 0.018), end-diastolic volume, and left atrial pressure all significantly increased. Stroke work, ejection fraction, and coronary blood flow were not significantly changed, and no signs of ischemia were seen on the ECG. The IABP raised average cardiac output by 31% (P = 0.012) and significantly raised blood pressure and flow to the brain while decreasing systemic vascular resistance. Left ventricular function and mean coronary blood flow did not change, but diastolic coronary flow became more important as shown by the increase in diastolic fraction from 64% to 95%. (P = 0.028). Average MR dropped by 7.5% (P = 0.025). In conclusion, application of the IABP during acute MR lowers aortic impedance, resulting in less MR and more output toward the aorta without changing left ventricular function.

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus.

PubMed

Cunha, Joao Paulo da; Lizarte, Fermino Sanches; Novais, Paulo Cezar; Gattas, Daniela; Carvalho, Camila Albuquerque Mello de; Tirapelli, Daniela Pretti da Cunha; Molina, Carlos Augusto Fernandes; Tirapelli, Luis Fernando; Tucci, Silvio

2017-01-01

To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

Aortic angiography

MedlinePlus

Angiography - aorta; Aortography; Abdominal aorta angiogram; Aortic arteriogram; Aneurysm - aortic arteriogram ... this needle. The catheter is moved into the aorta. The doctor can see live images of the ...

Neonatal aortic stenosis.

PubMed

Drury, Nigel E; Veldtman, Gruschen R; Benson, Lee N

2005-09-01

Neonatal aortic stenosis is a complex and heterogeneous condition, defined as left ventricular outflow tract obstruction at valvular level, presenting and often requiring treatment in the first month of life. Initial presentation may be catastrophic, necessitating hemodynamic, respiratory and metabolic resuscitation. Subsequent management is focused on maintaining systemic blood flow, either via a univentricular Norwood palliation or a biventricular route, in which the effective aortic valve area is increased by balloon dilation or surgical valvotomy. In infants with aortic annular hypoplasia but adequately sized left ventricle, the Ross-Konno procedure is also an attractive option. Outcomes after biventricular management have improved in recent years as a consequence of better patient selection, perioperative management and advances in catheter technology. Exciting new developments are likely to significantly modify the natural history of this disorder, including fetal intervention for the salvage of the hypoplastic left ventricle; 3D echocardiography providing better definition of valve morphology and aiding patient selection for a surgical or catheter-based intervention; and new transcutaneous approaches, such as duel beam echo, to perforate the valve.

Valve repair in aortic regurgitation without root dilatation--aortic valve repair.

PubMed

Lausberg, H F; Aicher, D; Kissinger, A; Langer, F; Fries, R; Schäfers, H-J

2006-02-01

Aortic valve repair was established in the context of aortic root remodeling. Variable results have been reported for isolated valve repair. We analyzed our experience with isolated valve repair and compared the results with those of aortic root remodeling. Between October 1995 and August 2003, isolated repair of the aortic valve was performed in 83 patients (REP), remodeling of the aortic valve in 175 patients (REMO). The demographics of the two groups were comparable (REP: mean age 54.4 +/- 20.7 yrs, male-female ratio 2.1 : 1; REMO: mean age 60.8 +/- 13.6 yrs, male-female ratio 2.4 : 1; p = ns). In both groups the number of bicuspid valves was comparable (REP: 41 %, REMO: 32 %; p = ns). All patients were followed by echocardiography for a cumulative follow-up of 8204 patient months (mean 32 +/- 23 months). Overall in-hospital mortality was 2.4 % in REP and 4.6 % in REMO ( p = 0.62). Systolic gradients were comparable in both groups (REP: 5.8 +/- 2.2, REMO: 6.5 +/- 3.1 mm Hg, p = 0.09). The mean degree of aortic regurgitation 12 months postoperatively was 0.8 +/- 0.7 after REP and 0.7 +/- 0.7 after REMO ( p = 0.29). Freedom from significant regurgitation (> or = II degrees ) after 5 years was 86 % in REP and 89 % in REMO ( p = 0.17). Freedom from re-operation after 5 years was 94.4 % in REP and 98.2 % in REMO ( p = 0.33). Aortic regurgitation without concomitant root dilatation can be treated effectively by aortic valve repair. The functional results are equivalent to those obtained with valve-preserving root replacement. Aortic valve repair appears to be an alternative to valve replacement in aortic regurgitation.

Long-Term Risk for Aortic Complications After Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Versus Marfan Syndrome.

PubMed

Itagaki, Shinobu; Chikwe, Joanna P; Chiang, Yuting P; Egorova, Natalia N; Adams, David H

2015-06-09

Bicuspid aortic valves are associated with valve dysfunction, ascending aortic aneurysm and dissection. Management of the ascending aorta at the time of aortic valve replacement (AVR) in these patients is controversial and has been extrapolated from experience with Marfan syndrome, despite the absence of comparative long-term outcome data. This study sought to assess whether the natural history of thoracic aortopathy after AVR in patients with bicuspid aortic valve disease is substantially different from that seen in patients with Marfan syndrome. In this retrospective comparison, outcomes of 13,205 adults (2,079 with bicuspid aortic valves, 73 with Marfan syndrome, and 11,053 control patients with acquired aortic valve disease) who underwent primary AVR without replacement of the ascending aorta in New York State between 1995 and 2010 were compared. The median follow-up time was 6.6 years. The long-term incidence of thoracic aortic dissection was significantly higher in patients with Marfan syndrome (5.5 ± 2.7%) compared with those with bicuspid valves (0.55 ± 0.21%) and control group patients (0.41 ± 0.08%, p < 0.001). Thoracic aortic aneurysms were significantly more likely to be diagnosed in late follow-up in patients with Marfan syndrome (10.8 ± 4.4%) compared with those with bicuspid valves (4.8 ± 0.8%) and control group patients (1.4 ± 0.2%) (p < 0.001). Patients with Marfan syndrome were significantly more likely to undergo thoracic aortic surgery in late follow-up (10.4 ± 4.3%) compared with those with bicuspid valves (2.5 ± 0.6%) and control group patients (0.50 ± 0.09%) (p < 0.001). The much higher long-term rates of aortic complications after AVR observed in patients with Marfan syndrome compared with those with bicuspid aortic valves confirm that operative management of patients with bicuspid aortic valves should not be extrapolated from Marfan syndrome and support discrete treatment algorithms for these different clinical entities

Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation.

PubMed

Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong; Lim, Hyun Kyo; Ryoo, Sungwoo

2016-11-01

Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. N(G)-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions.

Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis.

PubMed

Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana

2017-10-01

Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. ClinicalTrials.gov identifier: NCT00092677. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Further insights into normal aortic valve function: role of a compliant aortic root on leaflet opening and valve orifice area.

PubMed

Sripathi, Vangipuram Canchi; Kumar, Ramarathnam Krishna; Balakrishnan, Komarakshi R

2004-03-01

This study aims to find the fundamental differences in the mechanism of opening and closing of a normal aortic valve and a valve with a stiff root, using a dynamic finite element model. A dynamic, finite element model with time varying pressure was used in this study. Shell elements with linear elastic properties for the leaflet and root were used. Two different cases were analyzed: (1) normal leaflets inside a compliant root, and (2) normal leaflets inside a stiff root. A compliant aortic root contributes substantially to the smooth and symmetrical leaflet opening with minimal gradients. In contrast, the leaflet opening inside a stiff root is delayed, asymmetric, and wrinkled. However, this wrinkling is not associated with increased leaflet stresses. In compliant roots, the effective valve orifice area can substantially increase because of increased root pressure and transvalvular gradients. In stiff roots this effect is strikingly absent. A compliant aortic root contributes substantially to smooth and symmetrical leaflet opening with minimal gradients. The compliance also contributes much to the ability of the normal aortic valve to increase its effective valve orifice in response to physiologic demands of exercise. This effect is strikingly absent in stiff roots.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

PubMed

Beckmann, A; Hamm, C; Figulla, H R; Cremer, J; Kuck, K H; Lange, R; Zahn, R; Sack, S; Schuler, G C; Walther, T; Beyersdorf, F; Böhm, M; Heusch, G; Funkat, A K; Meinertz, T; Neumann, T; Papoutsis, K; Schneider, S; Welz, A; Mohr, F W

2012-07-01

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing

Trans-catheter aortic valve implantation after previous aortic homograft surgery.

PubMed

Drews, Thorsten; Pasic, Miralem; Buz, Semih; Unbehaun, Axel

2011-12-01

In patients with previous heart surgery, the operative risk is elevated during conventional aortic valve re-operations. Trans-catheter aortic valve implantation is a new method for the treatment of high-risk patients. Nevertheless, this new procedure carries potential risks in patients with previous homograft implantation in aortic position. Between April 2008 and February 2011, 345 consecutive patients (mean EuroSCORE (European System for Cardiac Operative Risk Evaluation): 38 ± 20%; mean Society of Thoracic Surgeons (STS) Mortality Score: 19 ± 16%; mean age: 80 ± 8 years; 111 men and 234 women) underwent trans-apical aortic valve implantation. In three patients, previous aortic homograft implantation had been performed. Homograft degeneration causing combined valve stenosis and incompetence made re-operation necessary. In all three patients, the aortic valve could be implanted using the trans-apical approach, and the procedure was successful. In two patients, there was slight paravalvular leakage of the aortic prosthesis and the other patient had slight central leakage. Neither ostium obstruction nor mitral valve damage was observed. Trans-catheter valve implantation can be performed successfully after previous homograft implantation. Particular care should be taken to achieve optimal valve positioning, not to obstruct the ostium of the coronary vessels due to the changed anatomic situation and not to cause annulus rupture. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure

NASA Technical Reports Server (NTRS)

Crandall, Craig G.; Engelke, Keith A.; Convertino, Victor A.; Raven, Peter B.

1994-01-01

To determine the effects of simulated microgravity on aortic baroreflex control of heart rate, we exposed seven male subjects to 15 days of bed rest in the 6 deg head-down position. The sensitivity of the aortic-cardiac baroreflex was determined during a steady-state phenylephrine-induced increase in mean arterial pressure combined with lower body negative pressure to counteract central venous pressure increases and neck pressure to offset the increased carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in mean arterial pressure between baseline conditions and aortic baroreceptor-isolated conditions (i.e., phenylephrine + lower body negative pressure + neck pressure stage). Fifteen days of head-down tilt increased the gain of the aortic-cardiac baroreflex. Reductions in blood volume and/or maximal aerobic capacity may represent the underlying mechanism(s) responsible for increased aortic baroreflex responsiveness after exposure to a ground-based analogue of microgravity.

Aortopathy in patients with bicuspid aortic valve stenosis: role of aortic root functional parameters.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Espinoza, Andres; Dubslaff, Georg; Fey, Beatrix; Theis, Bernhard; Petersen, Iver; Borger, Michael A; Kuntze, Thomas

2016-02-01

We prospectively examined functional characteristics of the aortic root and transvalvular haemodynamic flow in order to define factors associated with the severity of aortopathy in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. A total of 103 consecutive patients with BAV stenosis (mean age 61 ± 9 years, 66% male) underwent aortic valve replacement ± concomitant aortic surgery from January 2012 through March 2014. All patients underwent preoperative cardiac magnetic resonance imaging (MRI) in order to evaluate the systolic transvalvular flow and the following functional parameters: (i) angulation between the left ventricular outflow axis and the aortic root, (ii) geometrical orientation of residual aortic valve orifice and (iii) BAV cusp fusion pattern. MRI data were used to guide sampling of the ascending aorta during surgery [i.e. jet-sample from the area where the flow-jet impacts on the aortic wall and control sample from the opposite aortic wall (obtained from the aortotomy site)]. Aortopathy was quantified by means of a histological sum-score (0 to 21+) in each sample. A significant correlation was found between histological sum-score in the jet-sample and the angle between the LV outflow axis and the aortic root (r = 0.6, P = 0.007). Moreover, there was a linear correlation between proximal aortic diameter and the angle between systolic flow-jet and ascending aortic wall (r = 0.5, P = 0.006). Logistic regression identified the angle between the LV outflow axis and the aortic root (OR 1.1, P = 0.04) and the angle between the flow-jet and the aortic wall (OR 1.2, P = 0.001) as independent predictors of an indexed proximal aortic diameter ≥22 mm/m(2). Functional parameters of the aortic root may be used to predict the severity of aortopathy in patients with BAV stenosis, and may be useful in predicting future risk of aortic disease in such patients. © The Author 2015. Published by Oxford University Press on behalf of the European

Aortic cusp extension for surgical correction of rheumatic aortic valve insufficiency in children.

PubMed

Kalangos, Afksendiyos; Myers, Patrick O

2013-10-01

Surgical management of aortic insufficiency in the young is problematic because of the lack of an ideal valve substitute. Potential advantages of aortic valve repair include low incidences of thromboembolism and endocarditis, avoiding conduit replacements, the maintenance of growth potential, and improved quality of life. Aortic valve repair is still far from fulfilling the three key factors that have allowed the phenomenal development of mitral valve repair (standardization, reproducibility, and stable long-term results); however, techniques of aortic valve repair have been refined, and subsets of patients amenable to repair have been identified. We have focused on the oldest technique of aortic valve repair, cusp extension, focusing on children with rheumatic aortic insufficiency. Among 77 children operated from 2003 to 2007, there was one early death from ventricular failure and one late death from sudden cardiac arrhythmia. During a mean follow-up of 12.8 ± 5.9 years, there were 16 (20.5%) reoperations on the aortic valve, at a median of 3.4 years (range, 2 months to 18.3 years) from repair. Freedom from aortic valve reoperation was 96.2% ± 2.2% at 1 year, 94.9% ± 2.5% at 2 years, 88.5% ± 3.6% at 5 years, 81.7% ± 4.4% at 10 years, 79.7% ± 4.8% at 15 years, and 76.2% ± 5.7% at 20 years. Although aortic cusp extension is technically more demanding, it remains particularly more suitable in the context of evolving rheumatic aortic insufficiency in children with a small aortic annulus as a bridge surgical approach to late aortic valve replacement with a larger valvular prosthesis.

Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters.

PubMed

Zago, Vanessa Helena de Souza; Santos, José Eduardo Tanus dos; Danelon, Mirian Regina Gardin; Silva, Roger Marcelo Mesquita da; Panzoldo, Natália Baratella; Parra, Eliane Soler; Alexandre, Fernanda; Virgínio, Vítor Wilson de Moura; Quintão, Eder Carlos Rocha; Faria, Eliana Cotta de

2013-01-01

Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.

Early outcomes of transcatheter aortic valve replacement in patients with severe aortic stenosis: single center experience

PubMed Central

Bozkurt, Engin; Keleş, Telat; Durmaz, Tahir; Akçay, Murat; Ayhan, Hüseyin; Bayram, Nihal Akar; Aslan, Abdullah Nabi; Baştuğ, Serdal; Bilen, Emine

2014-01-01

Introduction Transcatheter aortic valve implantation is a promising alternative to high risk surgical aortic valve replacement. The procedure is mainly indicated in patients with severe symptomatic aortic stenosis who cannot undergo surgery or who are at very high surgical risk. Aim Description early results of our single-center experience with balloon expandable aortic valve implantation. Material and methods Between July 2011 and August 2012, we screened in total 75 consecutive patients with severe aortic stenosis and high risk for surgery. Twenty-one of them were found ineligible for transcatheter aortic valve implantation (TAVI) because of various reasons, and finally we treated a total of 54 patients with symptomatic severe aortic stenosis (AS) who could not be treated by open heart surgery (inoperable) because of high-risk criteria. The average age of the patients was 77.4 ±7.1; 27.8% were male and 72.2% were female. The number of patients in NYHA class II was 7 while the number of patients in class III and class IV was 47. Results The average mortality score of patients according to the STS scoring system was 8.5%. Pre-implantation mean and maximal aortic valve gradients were measured as 53.2 ±14.1 mm Hg and 85.5 ±18.9 mm Hg, respectively. Post-implantation mean and maximal aortic valve gradients were 9.0 ±3.0 and 18.2 ±5.6, respectively (p < 0.0001). The left ventricular ejection fraction was calculated as 54.7 ±14.4% before the operation and 58.0 ±11.1% after the operation (p < 0.0001). The duration of discharge after the operation was 5.29 days, and a statistically significant correlation between the duration of discharge after the operation and STS was found (r = 0385, p = 0.004). Conclusions We consider that with decreasing cost and increasing treatment experience, TAVI will be used more frequently in broader indications. Our experience with TAVI using the Edwards-Sapien XT (Edwards Lifesciences, Irvine, CA) devices suggests that this is an

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection

PubMed Central

Cikach, Frank S.; Koch, Christopher D.; Mead, Timothy J.; Galatioto, Josephine; Willard, Belinda B.; Emerton, Kelly B.; Eagleton, Matthew J.; Blackstone, Eugene H.; Ramirez, Francesco; Roselli, Eric E.; Apte, Suneel S.

2018-01-01

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID:29515038

Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

PubMed

Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

2018-03-08

Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

Snare-assisted anterograde balloon mitral and aortic valvotomy using Inoue balloon catheter.

PubMed

Krishnan, Mangalath N; Syamkumar, M D; Sajeev, C G; Venugopal, K; Johnson, Francis; Vinaykumar, D; Velayudhan, C C; Jayakumar, T G

2007-01-02

We performed concurrent antegrade mitral and aortic valvotomy using Inoue dilatation catheter in 3 cases of combined rheumatic mitral and aortic stenosis. Following mitral valvotomy by standard procedure, aortic valve was crossed with the help of a floatation catheter. Stiff long length guide wire was fixed in descending aorta using a snare. Inoue catheter was threaded over the wire across the aortic valve and aortic valvotomy completed. Mitral valve area increased from mean 1 cm2 to 2 cm2; aortic gradient dropped from mean of 97 mm to 36 mm. Concurrent anterograde balloon mitral and aortic valvotomy may be effective and safe.

Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

PubMed Central

Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

2015-01-01

AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. METHODS: Wild type, inducible nitric oxide synthase (iNOS)-/- and endothelial nitric oxide synthase (eNOS)-/- mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). RESULTS: SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS-/- PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS-/- PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS-/- or iNOS-/- mice. Thalidomide acutely increased plasma NOx in wild type and eNOS-/- mice but not iNOS-/- mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS

Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

PubMed

Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

2015-04-14

Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. Wild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS

Designing and Validation of One-Step T-ARMS-PCR for Genotyping the eNOS rs1799983 SNP

PubMed Central

Heidar, Mohammad Mehdi; Khatami, Mehri

2017-01-01

Background: The transversion of G to T (G894T) in human endothelial nitric oxide synthase (eNOS) gene has profound effects such as male infertility, recurrent miscarriage, multiple sclerosis and cardiovascular diseases. Objectives: Development of a new Multiplex Tetra-Primer Amplification Refractory Mutation System - Polymerase Chain Reaction (T-ARMS-PCR) for detection of rs1799983 (G894T) in the human eNOS was sought. Materials and Methods: A T-ARMS-PCR for rs1799983 polymorphism in a single-step PCR was carried out, and the results were confirmed by PCR-RFLP technique in 82 infertile men with varicocele. Results: The results showed that GG (varicocele infertile men), GT and TT genotypes appear to be 53.65%, 34.14%, and 12.19%, respectively. Full accordance between PCR-RFLP and T-ARMS-PCR methods for genotyping of rs1799983 polymorphism was found. Conclusions: This is the first work that describes a rapid, relatively cheap, high throughput detection of G894T polymorphism in eNOS that can be used in large scale clinical studies. PMID:29845071

Designing and Validation of One-Step T-ARMS-PCR for Genotyping the eNOS rs1799983 SNP.

PubMed

Heidar, Mohammad Mehdi; Khatami, Mehri

2017-01-01

Background: The transversion of G to T (G894T) in human endothelial nitric oxide synthase ( eNOS ) gene has profound effects such as male infertility, recurrent miscarriage, multiple sclerosis and cardiovascular diseases. Objectives: Development of a new Multiplex Tetra-Primer Amplification Refractory Mutation System - Polymerase Chain Reaction (T-ARMS-PCR) for detection of rs1799983 (G894T) in the human eNOS was sought. Materials and Methods: A T-ARMS-PCR for rs1799983 polymorphism in a single-step PCR was carried out, and the results were confirmed by PCR-RFLP technique in 82 infertile men with varicocele. Results: The results showed that GG (varicocele infertile men), GT and TT genotypes appear to be 53.65%, 34.14%, and 12.19%, respectively. Full accordance between PCR-RFLP and T-ARMS-PCR methods for genotyping of rs1799983 polymorphism was found. Conclusions: This is the first work that describes a rapid, relatively cheap, high throughput detection of G894T polymorphism in eNOS that can be used in large scale clinical studies.

Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

PubMed Central

Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

2014-01-01

VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

Aortic valve repair with autologous pericardial patch.

PubMed

Lausberg, Henning F; Aicher, Diana; Langer, Frank; Schäfers, Hans-Joachim

2006-08-01

Isolated aortic valve repair (AVR) has been gaining increasing interest in recent times. Results of isolated aortic valve repair have been reported to be variable. Various techniques have been utilized. We analyzed our experience with isolated valve repair using autologous pericardial patch plasty and compared the results to an age-matched collective with aortic valve repair without the use of additional material. Between January 1997 and June 2005, pericardial patch plasty of the aortic valve was performed in 42 patients (PATCH). During the same period, 42 patients after AVR without the use of additional material were age matched (NO-PATCH). Mean age in both groups was 52 years with a majority of male patients (PATCH ratio, 3.7:1; NO-PATCH ratio, 5:1). Valve anatomy was similar in both groups. All patients were followed by echocardiography for a cumulative follow-up of 2341 patient months (mean 28+/-23 months). No patient died in the hospital in neither group. The average systolic gradient was 5.9+/-2.2 mmHg in PATCH and 4.8+/-2.1 mmHg in NO-PATCH; p=0.17). Freedom from aortic regurgitation > or = II degrees was 87.8% in PATCH and 95.0% in NO-PATCH after 5 years (p=0.21). Freedom from reoperation was 97.6% in PATCH and 97.4% in NO-PATCH (p=0.96). Aortic regurgitation can be treated effectively by aortic valve repair using pericardial patch plasty. The functional results are satisfactory. With the application of this technique also more complex pathologies of the aortic valve can be addressed adequately thus extending the concept of valve preservation in patients with aortic regurgitation.

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.

PubMed

Silveira, Edna Aparecida; Siman, Fabiana Dayse Magalhães; de Oliveira Faria, Thaís; Vescovi, Marcos Vinícius Altoé; Furieri, Lorena Barros; Lizardo, Juliana Hott Fúcio; Stefanon, Ivanita; Padilha, Alessandra Simão; Vassallo, Dalton Valentim

2014-02-01

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Aortic stiffness and the balance between cardiac oxygen supply and demand: the Rotterdam Study.

PubMed

Guelen, Ilja; Mattace-Raso, Francesco Us; van Popele, Nicole M; Westerhof, Berend E; Hofman, Albert; Witteman, Jacqueline Cm; Bos, Willem Jan W

2008-06-01

Aortic stiffness is an independent predictor of cardiovascular morbidity and mortality. We investigated whether aortic stiffness, estimated as aortic pulse wave velocity, is associated with decreased perfusion pressure estimated as the cardiac oxygen supply potential. Aortic stiffness and aortic pressure waves, reconstructed from finger blood pressure waves, were obtained in 2490 older adults within the framework of the Rotterdam Study, a large population-based study. Cardiac oxygen supply and demand were estimated using pulse wave analysis techniques, and related to aortic stiffness by linear regression analyses after adjustment for age, sex, mean arterial pressure and heart rate. Cardiac oxygen demand, estimated as the Systolic Pressure Time Index and the Rate Pressure Product, increased with increasing aortic stiffness [0.27 mmHg s (95% confidence interval: 0.21; 0.34)] and [42.2 mmHg/min (95% confidence interval: 34.1; 50.3)], respectively. Cardiac oxygen supply potential estimated as the Diastolic Pressure Time Index decreased [-0.70 mmHg s (95% confidence interval: -0.86; -0.54)] with aortic stiffening. Accordingly, the supply/demand ratio Diastolic Pressure Time Index/Systolic Pressure Time Index -1.11 (95% confidence interval: -0.14; -0.009) decreased with increasing aortic stiffness. Aortic stiffness is associated with estimates of increased cardiac oxygen demand and a decreased cardiac oxygen supply potential. These results may offer additional explanation for the relation between aortic stiffness and cardiovascular morbidity and mortality.

VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

EPA Science Inventory

VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS.

Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and NHEERL, US EPA, Chapel Hill, North Ca...

VANADL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

EPA Science Inventory

VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS. Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and ORD, US EPA, Chapel Hill, North Carolina
V...

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

PubMed

Wong, Dennis T L; Bertaso, Angela G; Liew, Gary Y H; Thomson, Viji S; Cunnington, Michael S; Richardson, James D; Gooley, Robert; Lockwood, Siobhan; Meredith, Ian T; Worthley, Matthew I; Worthley, Stephen G

2013-04-01

Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Association between flow skewness and aortic dilatation in patients with aortic stenosis.

PubMed

Ha, Hojin; Koo, Hyun Jung; Lee, June Goo; Kim, Guk Bae; Kweon, Jihoon; Lee, Sang Joon; Kang, Joon Won; Lim, Tae Hwan; Kim, Dae Hee; Song, Jong Min; Kang, Duk Hyun; Song, Jae Kwan; Kim, Young Hak; Kim, Namkug; Yang, Dong Hyun

2017-12-01

We investigated association between hemodynamic characteristics and aortic dilatation in patients with severe aortic stenosis (AS). Eighty patients with severe AS (mean age, 67.2 ± 12.5 years) who underwent multi-detector computed tomography and phase-contrast magnetic resonance imaging at the ascending aorta were retrospectively analyzed. Patients with an ascending aorta diameter >4 cm had a significantly higher forward flow rate at systole (28.5 ± 6.0 vs. 36.2 ± 8.6 L min, P < 0.001), and retrograde flow rate at systole (11.3 ± 4.2 vs. 18.8 ± 5.8 L min, P < 0.001), fractional reverse ratio (a ratio of retrograde flow rate to forward flow rate; 34.1 ± 11.9% vs. 43.5 ± 18.0%, P = 0.014), flow skewness R skewness (a ratio of sum of forward and retrograde systole flow to net systole flow rate; 2.4 ± 0.7 vs. 3.2 ± 1.0, P < 0.001). The presence of bicuspid aortic valve (BAV; odds ratio [OR] 72.01, 95% confidence interval [CI] 10.57-490.46, P < 0.001), Left ventricular mass index (LVMI; OR 1.02 /g/m 2 ; CI 1.00-1.04, P = 0.043) and R skewness (OR 5.6 per 1, 95% CI 1.8-17.1, P = 0.001) were associated with aortic dilatation. BAV, LVMI, and increased R skewness in the ascending aorta are associated with aortic dilatation in patients with AS.

Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.

PubMed

Guo, Dong-chuan; Regalado, Ellen; Casteel, Darren E; Santos-Cortez, Regie L; Gong, Limin; Kim, Jeong Joo; Dyack, Sarah; Horne, S Gabrielle; Chang, Guijuan; Jondeau, Guillaume; Boileau, Catherine; Coselli, Joseph S; Li, Zhenyu; Leal, Suzanne M; Shendure, Jay; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Kim, Choel; Milewicz, Dianna M

2013-08-08

Gene mutations that lead to decreased contraction of vascular smooth-muscle cells (SMCs) can cause inherited thoracic aortic aneurysms and dissections. Exome sequencing of distant relatives affected by thoracic aortic disease and subsequent Sanger sequencing of additional probands with familial thoracic aortic disease identified the same rare variant, PRKG1 c.530G>A (p.Arg177Gln), in four families. This mutation segregated with aortic disease in these families with a combined two-point LOD score of 7.88. The majority of affected individuals presented with acute aortic dissections (63%) at relatively young ages (mean 31 years, range 17-51 years). PRKG1 encodes type I cGMP-dependent protein kinase (PKG-1), which is activated upon binding of cGMP and controls SMC relaxation. Although the p.Arg177Gln alteration disrupts binding to the high-affinity cGMP binding site within the regulatory domain, the altered PKG-1 is constitutively active even in the absence of cGMP. The increased PKG-1 activity leads to decreased phosphorylation of the myosin regulatory light chain in fibroblasts and is predicted to cause decreased contraction of vascular SMCs. Thus, identification of a gain-of-function mutation in PRKG1 as a cause of thoracic aortic disease provides further evidence that proper SMC contractile function is critical for maintaining the integrity of the thoracic aorta throughout a lifetime. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm.

PubMed

Roberts, William Clifford; Vowels, Travis James; Ko, Jong Mi; Filardo, Giovanni; Hebeler, Robert Frederick; Henry, Albert Carl; Matter, Gregory John; Hamman, Baron Lloyd

2011-03-01

There is debate concerning whether an aneurysmal ascending aorta should be replaced when associated with a dysfunctioning aortic valve that is to be replaced. To examine this issue, we divided the patients by type of aortic valve dysfunction-either aortic stenosis (AS) or pure aortic regurgitation (AR)-something not previously undertaken. Of 122 patients with ascending aortic aneurysm (unassociated with aortitis or acute dissection), the aortic valve was congenitally malformed (unicuspid or bicuspid) in 58 (98%) of the 59 AS patients, and in 38 (60%) of the 63 pure AR patients. Ascending aortic medial elastic fiber loss (EFL) (graded 0 to 4+) was zero or 1+ in 53 (90%) of the AS patients, in 20 (53%) of the 38 AR patients with bicuspid valves, and in all 12 AR patients with tricuspid valves unassociated with the Marfan syndrome. An unadjusted analysis showed that, among the 96 patients with congenitally malformed valves, the 38 AR patients had a significantly higher likelihood of 2+ to 4+ EFL than the 58 AS patients (crude odds ratio: 8.78; 95% confidence interval: 2.95, 28.13). These data strongly suggest that the type of aortic valve dysfunction-AS versus pure AR-is very helpful in predicting loss of aortic medial elastic fibers in patients with ascending aortic aneurysms and aortic valve disease.

Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

PubMed

Bretón-Romero, Rosa; Feng, Bihua; Holbrook, Monika; Farb, Melissa G; Fetterman, Jessica L; Linder, Erika A; Berk, Brittany D; Masaki, Nobuyuki; Weisbrod, Robert M; Inagaki, Elica; Gokce, Noyan; Fuster, Jose J; Walsh, Kenneth; Hamburg, Naomi M

2016-03-01

Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus. © 2016 American Heart

Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study

PubMed Central

Inghammar, Malin; Svanström, Henrik

2018-01-01

Abstract Objective To investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. Design Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection. Setting Sweden, July 2006 to December 2013. Participants 360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088). Main outcome measures Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment. Results Within the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection. Conclusions In a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm. PMID:29519881

Advances in aortic disease management: a year in review.

PubMed

Garg, Vinay; Ouzounian, Maral; Peterson, Mark D

2016-03-01

The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically.

Single center experience of aortic bypass graft for aortic arch obstruction in children.

PubMed

Shinkawa, Takeshi; Chipman, Carl; Holloway, Jessica; Tang, Xinyu; Gossett, Jeffrey M; Imamura, Michiaki

2017-01-01

The purpose of this study is to access the outcomes of aortic bypass graft placement in children. This is a retrospective review of all children having aortic bypass graft placement for aortic arch obstruction for the first time between 1982 and 2013 at a single institution. The actuarial survival and the freedom from aortic arch reoperation were calculated and compared between the groups. Seventy consecutive children underwent aortic bypass graft placements. The median age and body weight at the operation were 14 days and 3.6 kg. There were 7 early deaths, 6 late deaths, and 7 heart transplants during the median follow-up of 10.8 years (0.0-31.5 years). The actuarial transplant free survival was 64.7 % at 20 years and the freedom from aortic arch reoperation was 50.5 % at 10 years. Between the children younger than 1 year old and older than 1 year old, there were significant differences in actuarial transplant free survival (56.4 vs. 100 % at 15 years, p = 0.0042) and in the freedom from aortic arch reoperation (18.7 vs. 100 % at 10 years, p < 0.001). The children who received aortic bypass graft larger than 16 mm in size had no aortic arch reoperation at 15 years. The aortic bypass graft placement for aortic arch obstruction can be done with low mortality and morbidity for children who can receive bypass graft larger than 16 mm in size. However, it should be avoided for the neonates and infants except selected situations.

Evaluation of Protective Immune Responses Induced by Recombinant TrxLp and ENO2 Proteins against Toxoplasma gondii Infection in BALB/c Mice

PubMed Central

Wang, Meng; Yang, Xiao-Yu; Zhang, De-Lin

2016-01-01

Toxoplasma gondii is an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage of T. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified from Escherichia coli with pET-30a(+) expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+ T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8 ± 2.77 d), rTgENO2 (7.4 ± 1.81 d), and rTgTrxLp + rTgENO2 (8.38 ± 4.57 d) proteins showed significantly longer survival time than those that received Freund's adjuvant (6.78 ± 2.08 d) and PBS (6.38 ± 4.65 d) (χ 2 = 9.687, df = 4, P = 0.046). The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronic T. gondii infection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis. PMID:27803923

Left Ventricular Assist Device Implantation with Concomitant Aortic Valve and Ascending Aortic Replacement.

PubMed

Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

2018-01-01

Left ventricular assist device (LVAD) is nowadays a routine therapy for patients with advanced heart failure. We present the case of a 74-year-old male patient who was admitted to our center with terminal heart failure in dilated cardiomyopathy and ascending aortic aneurysm with aortic valve regurgitation. The LVAD implantation with simultaneous aortic valve and supracoronary ascending aortic replacement was successfully performed.

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

PubMed Central

English, Sean J.; Piert, Morand R.; Diaz, Jose A.; Gordon, David; Ghosh, Abhijit; D'Alecy, Louis G.; Whitesall, Steven E.; Sharma, Ashish K.; DeRoo, Elise P.; Watt, Tessa; Su, Gang; Henke, Peter K.; Eliason, Jonathan L.; Ailawadi, Gorav; Upchurch, Gilbert R.

2015-01-01

Objective To determine whether 18F-fluorodeoxyglucose (18F-FDG) micro–positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. Background An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. 18F-FDG PET can detect vascular inflammation in animal models and patients. Methods After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, β-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for 18F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1β, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. Results When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal 18F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1β (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02)expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. Conclusions With this AAA rupture model, increased prerupture 18F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. 18F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture. PMID:24651130

OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis.

PubMed

Sumi, Makoto; Sata, Masataka; Hashimoto, Ayako; Imaizumi, Takashi; Yanaga, Katsuhiko; Ohki, Takao; Mori, Toyoki; Nagai, Ryozo

2007-05-01

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.

Management of concomitant large aortic aneurysm and severe stenosis of aortic arc.

PubMed

Ren, Shiyan; Sun, Guang; Yang, Yuguang; Liu, Peng

2014-01-01

Primary large saccular aortic aneurysm with high grade stenosis of aortic arc is rare, and no standard therapy is available. We have encountered one case and successfully treated using a hybrid interventional approach. A 59-year-old woman with a 7-day history of headache, dizziness and chest pain, and a 5-year history of hypertension admitted and was diagnosed with transverse aortic aneurysm with sever aortic stenosis, the huge saccular aneurysm was located behind the transverse aortic arc. During surgery, a bypass with graft from ascending aorta to left external iliac artery was made initially in order to ensure the blood supply to the left leg, afterward, a 40 mm × 160 mm covered stent was implanted to cover the orifice of aneurysm and was used as a supporting anchorage in the descending aorta, a second covered stent (20 mm × 100 mm) was implanted to expand the stenosis of aortic arc. Follow-up at 1.5-year after surgery, the patient has been doing well without any surgical complication. A collateral pathway between internal mammary artery and inferior epigastric artery via the superior epigastric artery was found on3-dimensional reconstruction before surgery. Interruption of the compensatory arterial collateral pathway in the patient with severe stenosis of aortic arc should be prevented if possible in order to ensure the satisfactory perfusion of the lower limbs of the body.In conclusion, a patient with transverse aortic aneurysm accompanied with severe aortic stenosis can be treated by hybrid surgery.

[T(-786) --> C-polymorphism of the endothelial nitric oxide synthase promoter gene (eNOS) and exercise performance in sport].

PubMed

Drozdovs'ka, S B; Lysenko, O M; Dosenko, V Ie; Il'ïn, V M; Moĭbenko, O O

2013-01-01

Given the significant impact of the T(-786) --> C-polymorphism of the eNOS gene in the process of adaptation to physical stress, we aimed to investigate the effect of this polymorphism on physical performance in sportsmen and establish the possibility of its use as a marker of predisposition to the sport. DNA of 516 people, of which 195 qualified athletes and 321 people who had no experience of regular exercise was investigated. The frequency of genotypes and alleles of the T(-786) --> C-polymorphism of the eNOS gene in groups of athletes of different sports, the distribution of genotypes and alleles among athletes and those who are not involved in sports were studied. T allele frequency in a group of athletes on 6.4% (r(chi)2 = 0.03) than in control group. The association of the T allele of the T(-786) --> C-polymorphism of the eNOS gene with a predisposition for speed and power was established. In the group of athletes in speed and power sports, the T-allele frequency was higher than that in the control group by 12% (r(chi)2 = 0.002) and than in group endurance sports by 10% (r(chi)2 = 0.004). We found that the T(-786) --> C-polymorphism of the eNOS gene influence the power and efficiency ofthe functioning of the cardiorespiratory system of athletes during exercise.

Left Ventricular Assist Device Implantation with Concomitant Aortic Valve and Ascending Aortic Replacement

PubMed Central

Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

2018-01-01

Left ventricular assist device (LVAD) is nowadays a routine therapy for patients with advanced heart failure. We present the case of a 74-year-old male patient who was admitted to our center with terminal heart failure in dilated cardiomyopathy and ascending aortic aneurysm with aortic valve regurgitation. The LVAD implantation with simultaneous aortic valve and supracoronary ascending aortic replacement was successfully performed. PMID:29552039

Aortic arch atherosclerosis in patients with severe aortic stenosis can be argued by greater day-by-day blood pressure variability.

PubMed

Iwata, Shinichi; Sugioka, Kenichi; Fujita, Suwako; Ito, Asahiro; Matsumura, Yoshiki; Hanatani, Akihisa; Takagi, Masahiko; Di Tullio, Marco R; Homma, Shunichi; Yoshiyama, Minoru

2015-07-01

Although it is well known that the prevalence of aortic arch plaques, one of the risk factors for ischemic stroke, is high in patients with severe aortic stenosis, the underlying mechanisms are not well understood. Increased day-by-day blood pressure (BP) variability is also known to be associated with stroke; however, little is known on the association between day-by-bay BP variability and aortic arch atherosclerosis in patients with aortic stenosis. Our objective was to clarify the association between day-by-day BP variables (average values and variability) and aortic arch atherosclerosis in patients with severe aortic stenosis. The study population consisted of 104 consecutive patients (mean age 75 ± 8 years) with severe aortic stenosis who were scheduled for aortic valve replacement. BP was measured in the morning in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large (≥4 mm), ulcerated, or mobile plaques were defined as complex plaques using transesophageal echocardiography. Cigarette smoking and all systolic BP variables were associated with the presence of complex plaques (p < 0.05), whereas diastolic BP variables were not. Multiple regression analysis indicated that day-by-day mean systolic BP and day-by-day systolic BP variability remained independently associated with the presence of complex plaques (p < 0.05) after adjustment for age, male sex, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus. These findings suggest that higher day-by-day mean systolic BP and day-by-day systolic BP variability are associated with complex plaques in the aortic arch and consequently stroke risk in patients with aortic stenosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Continuous-flow cardiac assistance: effects on aortic valve function in a mock loop.

PubMed

Tuzun, Egemen; Rutten, Marcel; Dat, Marco; van de Vosse, Frans; Kadipasaoglu, Cihan; de Mol, Bas

2011-12-01

As the use of left ventricular assist devices (LVADs) to treat end-stage heart failure has become more widespread, leaflet fusion--with resul-tant aortic regurgitation--has been observed more frequently. To quantitatively assess the effects of nonpulsatile flow on aortic valve function, we tested a continuous-flow LVAD in a mock circulatory system (MCS) with an interposed valve. To mimic the hemodynamic characteristics of LVAD patients, we utilized an MCS in which a Jarvik 2000 LVAD was positioned at the base of a servomotor-operated piston pump (left ventricular chamber). We operated the LVAD at 8000 to 12,000 rpm, changing the speed in 1000-rpm increments. At each speed, we first varied the outflow resistance at a constant stroke volume, then varied the stroke volume at a constant outflow resistance. We measured the left ventricular pressure, aortic pressure, pump flow, and total flow, and used these values to compute the change, if any, in the aortic duty cycle (aortic valve open time) and transvalvular aortic pressure loads. Validation of the MCS was demonstrated by the simulation of physiologic pressure and flow waveforms. At increasing LVAD speeds, the mean aortic pressure load steadily increased, while the aortic duty cycle steadily decreased. Changes were consistent for each MCS experimental setting, despite variations in stroke volume and outflow resistance. Increased LVAD flow results in an impaired aortic valve-open time due to a pressure overload above the aortic valve. Such an overload may initiate structural changes, causing aortic leaflet fusion and/or regurgitation. Copyright © 2011 Elsevier Inc. All rights reserved.

Incidence and crash mechanisms of aortic injury during the past decade.

PubMed

Schulman, Carl I; Carvajal, Daniel; Lopez, Peter P; Soffer, Dror; Habib, Fahim; Augenstein, Jeffrey

2007-03-01

Aortic injuries were traditionally thought to be the result of severe frontal crashes. Newer data has suggested other crash types such as nearside crashes may also be important in aortic injury. We hypothesized the implementation of recent safety measures would decrease the incidence of aortic injury associated with fatal motor vehicle crashes. The autopsy reports of all traffic fatalities for motor vehicle occupants in a large urban county for the years 1993 to 2004 were examined. The demographics, impact types, safety measures used, and the presence of any aortic injury were recorded. Trends were evaluated for significance by weighted linear regression. The incidence of aortic injury associated with fatal motor vehicle crashes has remained unchanged during the past 12 years (r = 0.057, p = 0.45). There is a trend toward decreased aortic injuries associated with frontal crashes (r = 0.26, p = 0.089) but no change in aortic injuries associated with nearside or farside crashes (r = 0.053, p = 0.47), when the crash resulted in a fatality. This is despite an increase in seat belt use and increased presence of airbags during the same time period. Despite improved safety measures designed to minimize the occurrence of aortic injuries, the incidence of blunt aortic injury in fatal motor vehicle crashes has not decreased during the past decade. Although not statistically significant, there is a trend toward decreased frontal impacts in fatal motor vehicle crashes associated with aortic injuries. The nearside crash mechanism continues to play a prominent role, and efforts at improving vehicle safety should be focused on crash mechanisms as they relate to aortic injury.

Pravastatin reduces Marfan aortic dilation.

PubMed

McLoughlin, Darren; McGuinness, Jonathan; Byrne, John; Terzo, Eloisa; Huuskonen, Vilhelmiina; McAllister, Hester; Black, Alexander; Kearney, Sinead; Kay, Elaine; Hill, Arnold D K; Dietz, Harry C; Redmond, J Mark

2011-09-13

The sequelae of aortic root dilation are the lethal consequences of Marfan syndrome. The root dilation is attributable to an imbalance between deposition of matrix elements and metalloproteinases in the aortic medial layer as a result of excessive transforming growth factor-beta signaling. This study examined the efficacy and mechanism of statins in attenuating aortic root dilation in Marfan syndrome and compared effects to the other main proposed preventative agent, losartan. Marfan mice heterozygous for a mutant allele encoding a cysteine substitution in fibrillin-1 (C1039G) were treated daily from 6 weeks old with pravastatin 0.5 g/L or losartan 0.6 g/L. The end points of aortic root diameter (n=25), aortic thickness, and architecture (n=10), elastin volume (n=5), dp/dtmax (maximal rate of change of pressure) (cardiac catheter; n=20), and ultrastructural analysis with stereology (electron microscopy; n=5) were examined. The aortic root diameters of untreated Marfan mice were significantly increased in comparison to normal mice (0.161 ± 0.001 cm vs 0.252 ± 0.004 cm; P<0.01). Pravastatin (0.22 ± 0.003 cm; P<0.01) and losartan (0.221 ± 0.004 cm; P<0.01) produced a significant reduction in aortic root dilation. Both drugs also preserved elastin volume within the medial layer (pravastatin 0.23 ± 0.02 and losartan 0.29 ± 0.03 vs untreated Marfan 0.19 ± 0.02; P=0.01; normal mice 0.27 ± 0.02). Ultrastructural analysis showed a reduction of rough endoplasmic reticulum in smooth muscle cells with pravastatin (0.022 ± 0.004) and losartan (0.013 ± 0.001) compared to untreated Marfan mice (0.035 ± 0.004; P<0.01). Statins are similar to losartan in attenuating aortic root dilation in a mouse model of Marfan syndrome. They appear to act through reducing the excessive protein manufacture by vascular smooth muscle cells, which occurs in the Marfan aorta. As a drug that is relatively well-tolerated for long-term use, it may be useful clinically.

Aortic wrapping for a dilated ascending aorta in bicuspid aortic stenosis.

PubMed

Choi, Min Suk; Jeong, Dong Seop; Lee, Hae Young; Sung, Kiick; Kim, Wook Sung; Lee, Young Tak; Park, Pyo Won

2015-01-01

Ascending aorta wrapping is rarely recommended for the management of dilated aorta, because of late complications. The aim of the present study was to analyze the early and late outcomes of the aortic wrapping technique at the time of aortic valve replacement (AVR) for bicuspid aortic stenosis (BAS). Among patients who underwent primary AVR for BAS between 2002 and 2011, 79 who underwent ascending aortic wrapping (wrapping group) were compared with 144 patients who underwent AVR alone. The preoperative ascending aortic diameters were larger in the wrapping group (40.9±4.2 mm vs. 48.6±4.0 mm, P<0.001). Operative technique was to wrap the ascending aorta transversely with a semi-elliptically resected Dacron graft. The follow-up for the wrapping group was 76.5±35.5 (median 71.1) months. There were no early deaths. Early and late morbidity did not differ between groups. The 24 late deaths, including 10 cardiac-related deaths, occurred in the entire group; 3 sudden deaths occurred only in the AVR group. The 10-year overall survival in the wrapping group was higher than the AVR group (88.1±6.8% vs. 80.0±4.6%, P=0.048). No late aortic complications were detected. The aortic diameter was reduced from 49.5±4.1 mm to 45.3±5.0 mm after wrapping (P<0.001). The aortic wrapping technique may be an option for treating a moderately dilated ascending aorta in selected patients undergoing AVR for BAS. Longer follow-up, however, is necessary to verify later complications.

Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm

PubMed Central

Sun, Jingyuan; Deng, Hongping; Zhou, Zhen

2018-01-01

Abdominal aortic aneurysm (AAA) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for AAA. However, so far, it is unclear whether such drugs have any beneficial effect on AAA prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that AAA is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of AAA formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in AAA treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful AAA medications and offer a solution to this treatment challenge. It is now believed that AAA and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on AAA formation, especially after taking into account the importance of endothelium in the development of AAA. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for AAA, could be

Transcatheter aortic valve replacement

MedlinePlus

... fully will restrict blood flow. This is called aortic stenosis. If there is also a leak, it is ... TAVR is used for people with severe aortic stenosis who aren't ... valve . In adults, aortic stenosis usually occurs due to calcium ...

Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation

PubMed Central

Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong

2016-01-01

Purpose Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Materials and Methods Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. Results SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. NG-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. Conclusion These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions. PMID:27593859

Aortic Wave Dynamics and Its Influence on Left Ventricular Workload

NASA Astrophysics Data System (ADS)

Pahlevan, Niema; Gharib, Morteza

2010-11-01

Clinical and epidemiologic studies have shown that hypertension plays a key role in development of left ventricular (LV) hypertrophy and ultimately heart failure mostly due to increased LV workload. Therefore, it is crucial to diagnose and treat abnormal high LV workload at early stages. The pumping mechanism of the heart is pulsatile, thus it sends pressure and flow wave into the compliant aorta. The wave dynamics in the aorta is dominated by interplay of heart rate (HR), aortic rigidity, and location of reflection sites. We hypothesized that for a fixed cardiac output (CO) and peripheral resistance (PR), interplay of HR and aortic compliance can create conditions that minimize LV power requirement. We used a computational approach to test our hypothesis. Finite element method with direct coupling method of fluid-structure interaction (FSI) was used. Blood was assumed to be incompressible Newtonian fluid and aortic wall was considered elastic isotropic. Simulations were performed for various heart rates and aortic rigidities while inflow wave, CO, and PR were kept constant. For any aortic compliance, LV power requirement becomes minimal at a specific heart rate. The minimum shifts to higher heart rates as aortic rigidity increases.

Preservation of the bicuspid aortic valve.

PubMed

Schäfers, Hans-Joachim; Aicher, Diana; Langer, Frank; Lausberg, Henning F

2007-02-01

Bicuspid anatomy of the aortic valve is a common reason for aortic regurgitation and is associated with aortic dilatation in more than 50% of patients. We have observed different patterns of aortic dilatation and used different approaches preserving the valve. Between October 1995 and February 2006, a regurgitant bicuspid valve was repaired in 173 patients. The aorta was normal in 57 patients who underwent isolated repair. Aortic dilatation mainly above commissural level (n = 38) was treated by separate valve repair plus supracommissural aortic replacement. In 78 patients, aortic dilatation involved the root and was treated by root remodeling. Hospital mortality and perioperative morbidity were low in all three groups. Myocardial ischemia was significantly shorter in repair plus aortic replacement than remodeling (p < 0.001). Freedom from aortic regurgitation II or greater at 5 years varied between 91% and 96%. Freedom from reoperation at 5 years was 97% after remodeling, but only 53% after repair plus aortic replacement (p = 0.33). Symmetric prolapse was the most frequent cause for reoperation. The long-term stability of bicuspid aortic valve repair is excellent in the absence of aortic pathology. In the presence of aortic dilatation, root remodeling leads to equally stable valve durability. In patients with less pronounced root dilatation, separate valve repair plus aortic replacement may be a less complex alternative. Symmetric prolapse should be avoided if the ascending aorta is replaced.

Aortic expansion rate in patients with dilated post-stenotic ascending aorta submitted only to aortic valve replacement long-term follow-up.

PubMed

Gaudino, Mario; Anselmi, Amedeo; Morelli, Mauro; Pragliola, Claudio; Tsiopoulos, Vasileios; Glieca, Franco; Possati, Gianfederico

2011-08-02

This study was conceived to describe the evolution of aortic dimensions in patients with moderate post-stenotic ascending aorta dilation (50 to 59 mm) submitted to aortic valve replacement (AVR) alone. The appropriate treatment of post-stenotic ascending aorta dilation has been poorly investigated. Ninety-three patients affected by severe isolated calcific aortic valve stenosis in the tricuspid aortic valve accompanied by moderate dilation of the ascending aorta (50 to 59 mm) were submitted to AVR only. All patients were followed for a mean of 14.7 ± 4.8 years by means of periodic clinical evaluations and echocardiography and tomography scans of the thorax. Operative mortality was 1.0% (1 patient). During the follow-up, 16 patients died and 2 had to be reoperated for valve dysfunction. No patients experienced acute aortic events (rupture, dissection, pseudoaneurysm), and no patient had to be reoperated on the aorta. There was not a substantial increase in aortic dimensions: mean aortic diameter was 57 ± 11 mm at the end of the follow-up versus 56 ± 02 mm pre-operatively (p = NS). The mean ascending aorta expansion rate was 0.3 ± 0.2 mm/year. In the absence of connective tissue disorders, AVR alone is sufficient to prevent further aortic expansion in patients with moderate post-stenotic dilation of the ascending aorta. Aortic replacement can probably be reserved for patients with a long life expectancy. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Opening and closing characteristics of the aortic valve after valve-sparing procedures using a new aortic root conduit.

PubMed

De Paulis, R; De Matteis, G M; Nardi, P; Scaffa, R; Buratta, M M; Chiariello, L

2001-08-01

The durability of aortic valve-sparing procedures is negatively affected by increased leaflet stress in the absence of normally shaped sinuses of Valsalva. We compared valve motion after remodeling procedures using a standard conduit and a specifically designed aortic root conduit. Echocardiographic studies of the aortic valve dynamics were performed in 14 patients after remodeling of the aortic root (7 standard conduits, group A; 7 new conduits, group B) and in 7 controls (group C). Opening and closing leaflet velocities and percent of slow closing leaflet displacement were measured. Root distensibility and the pressure strain of the elastic modulus were measured at all root levels. Root distensibility and the pressure strain of the elastic modulus were different in group A and B only at the sinuses (p < 0.001). Opening and closing leaflet velocities were not different among groups. Slow closing leaflet displacement was markedly more evident in group B patients (24.2%+/-1.9% versus 2.5%+/-1.9% in group A, p < 0.001) and similar to controls (22.1%+/-7.9%). The new conduit guarantees dynamic features of the aortic valve leaflets superior to those obtained with standard conduits and more similar to normal subjects.

NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation.

PubMed

Sánchez-Gómez, Francisco J; Calvo, Enrique; Bretón-Romero, Rosa; Fierro-Fernández, Marta; Anilkumar, Narayana; Shah, Ajay M; Schröder, Katrin; Brandes, Ralf P; Vázquez, Jesús; Lamas, Santiago

2015-12-01

Laminar shear stress (LSS) triggers signals that ultimately result in atheroprotection and vasodilatation. Early responses are related to the activation of specific signaling cascades. We investigated the participation of redox-mediated modifications and in particular the role of hydrogen peroxide (H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular endothelial cells to short periods of LSS (12 dyn/cm(2)) resulted in the generation of superoxide radical anion as detected by the formation of 2-hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was corroborated by the increase in the fluorescence of the specific peroxide sensor HyPer. By using biotinylated dimedone we detected increased total protein sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4 (NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to identify the phosphatase SHP2 as a protein susceptible to sulfenylation under LSS. Given the dependence of FAK activity on SHP2 function, we explored the role of FAK under LSS conditions. FAK activation and subsequent endothelial NO synthase (eNOS) phosphorylation were promoted by LSS and both processes were dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4-null mice. These results support the idea that LSS elicits redox-sensitive signal transduction responses involving NOX4-dependent generation of hydrogen peroxide, SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation. Copyright © 2015 Elsevier Inc. All rights reserved.

Transfemoral aortic valve implantation in severe aortic stenosis patients with prior mitral valve prosthesis

PubMed Central

Sarı, Cenk; Baştuğ, Serdal; Kasapkara, Hacı Ahmet; Durmaz, Tahir; Keleş, Telat; Akçay, Murat; Aslan, Abdullah Nabi; Bayram, Nihal Akar; Bozkurt, Engin

2015-01-01

Introduction Transcatheter aortic valve implantation for severe symptomatic aortic stenosis in patients with a previous mitral valve prosthesis is technically challenging, and pre-procedural comprehensive assessment of these patients before transcatheter aortic valve implantation is vital for an uncomplicated and successful procedure. Aim We want to share our experience with transcatheter aortic valve implantation in patients with a preexisting functional mitral valve prosthesis and describe a series of important technical and pre-procedural details. Material and methods At our center, 135 patients with symptomatic severe aortic stenosis were treated with transcatheter aortic valve implantation. Six of them with a preexisting mitral valve prosthesis received an Edwards SAPIEN XT valve through the transfemoral route. Results Transcatheter aortic valve implantation was performed successfully in all 6 patients without any deformation of the cobalt-chromium/steel stents of the aortic valve bioprosthesis. Also no distortion or malfunction in the mitral valve prosthesis was observed after the procedure. There were no complications during the hospitalization period. Post-procedural echocardiography revealed no or mild aortic paravalvular regurgitation and normal valve function in all the patients. In addition, serial echocardiographic examination demonstrated that both the stability and function of the aortic and mitral prosthetic valves were normal without any deterioration in the gradients and the degree of the regurgitation at long-term follow-ups. Conclusions Our experience confirms that transcatheter aortic valve implantation is technically feasible in patients with previous mitral valve replacement but comprehensive evaluation of patients by multimodal imaging techniques such as transesophageal echocardiography and multislice computed tomography is mandatory for a successful and safe procedure. PMID:26677380

Dual Role of Endothelial Nitric Oxide Synthase in Oxidized LDL-Induced, p66Shc-Mediated Oxidative Stress in Cultured Human Endothelial Cells

PubMed Central

Shi, Yi; Lüscher, Thomas F.; Camici, Giovanni G.

2014-01-01

Background The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation. Methods and Results Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2 -). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc phosphorylation, suggesting that basal NO production inhibits O2 - production. oxLDL-induced, p66Shc-mediated O2- was prevented by eNOS inhibition, suggesting that when cells are stimulated with oxLDL eNOS is a source of reactive oxygen species. Endogenous or exogenous NO donors, prevented p66Shc activation and reduced O2- production. Treatment with tetrahydrobiopterin, an eNOS cofactor, restored eNOS uncoupling, prevented p66Shc activation, and reduced O2- generation. However, late treatment with tetrahydropterin did not yield the same result suggesting that eNOS uncoupling is the primary source of reactive oxygen species. Conclusions The present study reports that in primary cultured HAEC treated with oxLDL, p66Shc-mediated oxidative stress is derived from eNOS uncoupling. This finding contributes novel information on the mechanisms of p66Shc activation and its dual interaction with eNOS underscoring the importance eNOS uncoupling as a putative antioxidant therapeutical target in endothelial dysfunction as observed in cardiovascular disease. PMID:25247687

Dual role of endothelial nitric oxide synthase in oxidized LDL-induced, p66Shc-mediated oxidative stress in cultured human endothelial cells.

PubMed

Shi, Yi; Lüscher, Thomas F; Camici, Giovanni G

2014-01-01

The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation. Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2-). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc phosphorylation, suggesting that basal NO production inhibits O2- production. oxLDL-induced, p66Shc-mediated O2- was prevented by eNOS inhibition, suggesting that when cells are stimulated with oxLDL eNOS is a source of reactive oxygen species. Endogenous or exogenous NO donors, prevented p66Shc activation and reduced O2- production. Treatment with tetrahydrobiopterin, an eNOS cofactor, restored eNOS uncoupling, prevented p66Shc activation, and reduced O2- generation. However, late treatment with tetrahydropterin did not yield the same result suggesting that eNOS uncoupling is the primary source of reactive oxygen species. The present study reports that in primary cultured HAEC treated with oxLDL, p66Shc-mediated oxidative stress is derived from eNOS uncoupling. This finding contributes novel information on the mechanisms of p66Shc activation and its dual interaction with eNOS underscoring the importance eNOS uncoupling as a putative antioxidant therapeutical target in endothelial dysfunction as observed in cardiovascular disease.

Increasing plasma free fatty acids in healthy subjects induces aortic distensibility changes seen in obesity.

PubMed

Rider, Oliver J; Holloway, Cameron J; Emmanuel, Yaso; Bloch, Edward; Clarke, Kieran; Neubauer, Stefan

2012-05-01

Elevated free fatty acid (FFA) levels are known to impair aortic elastic function. In obesity, FFA levels are elevated and aortic distensibility (AD) reduced in a pattern that predominantly affects the distal aorta. Despite this, the role of FFAs in obesity-related aortic stiffness remains unclear. Using vascular MRI, we aimed to determine if (1) FFA level correlated with AD in obesity; and (2) whether elevating FFA acutely and subacutely in normal-weight subjects reproduced the distal pattern of AD change in obesity. To do this, regional AD was recorded in 35 normal-weight and 70 obese subjects and then correlated with FFA levels. When compared with normal weight, obesity was associated with reduced AD in a pattern predominantly affecting the distal aorta (ascending aorta by -22%, proximal descending aorta by -25%, and abdominal aorta by -35%; P<0.001). After controlling for age, blood pressure, and body mass index, FFA levels remained negatively correlated with abdominal AD (r=-0.43, P<0.01). In 2 further normal-weight groups, AD was recorded before and after elevation of FFA levels with intralipid infusion (by +535%, n=9) and a 5-day high-fat, low-carbohydrate diet (by +48%, n=14). Both intralipid infusion and a low-carbohydrate diet resulted in reduced abdominal AD (infusion -22%, diet -28%; both P<0.05), reproducing the distal pattern AD reduction seen in obesity. These findings suggest that elevated FFA impair AD in obesity and provide a potential therapeutic target to improve aortic elastic function in obesity.

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

PubMed Central

Hamatani, Yasuhiro; Ishibashi-Ueda, Hatsue; Nagai, Toshiyuki; Sugano, Yasuo; Kanzaki, Hideaki; Yasuda, Satoshi; Fujita, Tomoyuki; Kobayashi, Junjiro; Anzai, Toshihisa

2016-01-01

Background Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated. Methods and Results We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients’ backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35). Conclusions Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV. PMID:27479126

Smooth Muscle Cells Isolated from Thoracic Aortic Aneurysms Exhibit Increased Genomic Damage, but Similar Tendency for Apoptosis

PubMed Central

Serhatli, Muge; Kacar, Omer; Adiguzel, Zelal; Tuncer, Altug; Hayran, Mutlu; Baysal, Kemal

2012-01-01

Aortic aneurysms (AA) are characterized by structural deterioration leading to progressive dilation. During the development of AA, two key structural changes are pronounced, one being degradation of extracellular matrix and the other loss of smooth muscle cells (SMCs) through apoptosis. Reactive oxygen species (ROS) are produced above physiological levels in dilated (aneurismal) part of the aorta compared to the nondilated part and they are known to be associated with both the extracellular matrix degradation and the loss of SMCs. In this study, we hypothesized that aneurismal SMCs are more prone to apoptosis and that at least some cells undergo apoptosis due to elevated ROS in the aortic wall. To test this hypothesis, we first isolated SMCs from thoracic aneurismal tissue and compared their apoptotic tendency with normal SMCs in response to H2O2, oxidized sterol, or UV treatment. Exposed cells exhibited morphological changes characteristic of apoptosis, such as cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) further confirmed the fragmentation of nuclear DNA in these cells. Vascular SMCs were analyzed for their micronuclei (MN) and binucleate (BN) frequency as indicators of genomic abnormality. These data were then compared to patient parameters, including age, gender, hypertension, or aortic diameter for existing correlations. While the tendency for apoptosis was not significantly different compared to normal cells, both the %MN and %BN were higher in aneurismal SMCs. The data suggest that there is increased DNA damage in TAA samples, which might play a pivotal role in disease development. PMID:22871164

Modelling of aortic aneurysm and aortic dissection through 3D printing.

PubMed

Ho, Daniel; Squelch, Andrew; Sun, Zhonghua

2017-03-01

The aim of this study was to assess if the complex anatomy of aortic aneurysm and aortic dissection can be accurately reproduced from a contrast-enhanced computed tomography (CT) scan into a three-dimensional (3D) printed model. Contrast-enhanced cardiac CT scans from two patients were post-processed and produced as 3D printed thoracic aorta models of aortic aneurysm and aortic dissection. The transverse diameter was measured at five anatomical landmarks for both models, compared across three stages: the original contrast-enhanced CT images, the stereolithography (STL) format computerised model prepared for 3D printing and the contrast-enhanced CT of the 3D printed model. For the model with aortic dissection, measurements of the true and false lumen were taken and compared at two points on the descending aorta. Three-dimensional printed models were generated with strong and flexible plastic material with successful replication of anatomical details of aortic structures and pathologies. The mean difference in transverse vessel diameter between the contrast-enhanced CT images before and after 3D printing was 1.0 and 1.2 mm, for the first and second models respectively (standard deviation: 1.0 mm and 0.9 mm). Additionally, for the second model, the mean luminal diameter difference between the 3D printed model and CT images was 0.5 mm. Encouraging results were achieved with regards to reproducing 3D models depicting aortic aneurysm and aortic dissection. Variances in vessel diameter measurement outside a standard deviation of 1 mm tolerance indicate further work is required into the assessment and accuracy of 3D model reproduction. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Thoracic Endovascular Aortic Repair With Single/Double Chimney Technique for Aortic Arch Pathologies.

PubMed

Wang, Tun; Shu, Chang; Li, Ming; Li, Quan-Ming; Li, Xin; Qiu, Jian; Fang, Kun; Dardik, Alan; Yang, Chen-Zi

2017-06-01

To summarize a single-center experience using the single/double chimney technique in association with thoracic endovascular aortic repairs (TEVAR) for aortic arch pathologies. From November 2007 to March 2016, 122 patients (mean age 50.4±12.7 years, range 29-80; 92 men) with aortic arch pathologies underwent TEVAR combined with single (n=101) or double (n=21) chimney grafts to reconstruct the supra-aortic branches: 21 innominate arteries, 114 left common carotid arteries, and 8 left subclavian arteries (LSA). Pathologies included type B aortic dissection (n=47), aortic arch dissection (n=49), retrograde type A aortic dissection (n=8), thoracic aortic aneurysm (n=7), penetrating aortic arch ulcer (n=9), and post-TEVAR type I endoleak (n=2). Follow-up examinations included computed tomography at 0.5, 3, 6, and 12 months and yearly thereafter. The aortic stent-grafts were deployed in zone 0 (n=21), zone 1 (n=93), and zone 2 (n=8). One (0.8%) of the 122 patients died at 4 days due to a perforated peptic ulcer. Type Ia endoleaks were found intraoperatively in 13 (10.7%) patients, including 3 with the double chimney technique. Type II endoleaks occurred in 6 (4.9%) patients; 3 were treated with duct occluders in the LSA. Postoperative chimney graft migration occurred in 1 (0.8%) patient with double chimneys; additional stent-grafts were deployed in both chimneys. Median follow-up was 32.3 months, during which 1 (0.8%) patient died after a stroke at 3 months. Chimney stent-graft patency was observed in the remaining 120 patients. Two (1.7%) secondary TEVARs were performed for distal aortic dissection. Nine asymptomatic type Ia endoleaks and 1 type II endoleak persisted in follow-up; a type II endoleak in 1 patient with Marfan syndrome sealed in 52 months. TEVAR with the chimney technique provides a safe, minimally invasive alternative with good chimney graft patency and low postoperative mortality during midterm follow-up. The double chimney technique should be used

Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR.

PubMed

Musa, Tarique Al; Uddin, Akhlaque; Fairbairn, Timothy A; Dobson, Laura E; Sourbron, Steven P; Steadman, Christopher D; Motwani, Manish; Kidambi, Ananth; Ripley, David P; Swoboda, Peter P; McDiarmid, Adam K; Erhayiem, Bara; Oliver, James J; Blackman, Daniel J; Plein, Sven; McCann, Gerald P; Greenwood, John P

2016-06-10

Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV). A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m. Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.

Neurotrophin 3 upregulates proliferation and collagen production in human aortic valve interstitial cells: a potential role in aortic valve sclerosis.

PubMed

Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong

2017-06-01

Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society.

Functional Aortic Root Parameters and Expression of Aortopathy in Bicuspid Versus Tricuspid Aortic Valve Stenosis.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Fey, Beatrix; Dubslaff, Georg; Theis, Bernhard; Petersen, Iver; Gutberlet, Matthias; Borger, Michael A; Kuntze, Thomas

2016-04-19

The correlation between bicuspid aortic valve (BAV) disease and aortopathy is not fully defined. This study aimed to prospectively analyze the correlation between functional parameters of the aortic root and expression of aortopathy in patients undergoing surgery for BAV versus tricuspid aortic valve (TAV) stenosis. From January 1, 2012 through December 31, 2014, 190 consecutive patients (63 ± 8 years, 67% male) underwent aortic valve replacement ± proximal aortic surgery for BAV stenosis (n = 137, BAV group) and TAV stenosis (n = 53, TAV group). All patients underwent pre-operative cardiac magnetic resonance imaging to evaluate morphological/functional parameters of the aortic root. Aortic tissue was sampled during surgery on the basis of the location of eccentric blood flow contact with the aortic wall, as determined by cardiac magnetic resonance (i.e., jet sample and control sample). Aortic wall lesions were graded using a histological sum score (0 to 21). The largest cross-sectional aortic diameters were at the mid-ascending level in both groups and were larger in BAV patients (40.2 ± 7.2 mm vs. 36.6 ± 3.3 mm, respectively, p < 0.001). The histological sum score was 2.9 ± 1.4 in the BAV group versus 3.4 ± 2.6 in the TAV group (p = 0.4). The correlation was linear and comparable between the maximum indexed aortic diameter and the angle between the left ventricular outflow axis and aortic root (left ventricle/aorta angle) in both groups (BAV group: r = 0.6, p < 0.001 vs. TAV group r = 0.45, p = 0.03, z = 1.26, p = 0.2). Logistic regression identified the left ventricle/aorta angle as an indicator of indexed aortic diameter >22 mm/m(2) (odds ratio: 1.2; p < 0.001). Comparable correlation patterns between functional aortic root parameters and expression of aortopathy are found in patients with BAV versus TAV stenosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prognostic Implications of Raphe in Bicuspid Aortic Valve Anatomy.

PubMed

Kong, William K F; Delgado, Victoria; Poh, Kian Keong; Regeer, Madelien V; Ng, Arnold C T; McCormack, Louise; Yeo, Tiong Cheng; Shanks, Miriam; Parent, Sarah; Enache, Roxana; Popescu, Bogdan A; Liang, Michael; Yip, James W; Ma, Lawrence C W; Kamperidis, Vasileios; van Rosendael, Philippe J; van der Velde, Enno T; Ajmone Marsan, Nina; Bax, Jeroen J

2017-03-01

[24.4%] at 5 years) vs patients without raphe (30 [14.0%] at 1 year, 32 [15.0%] at 2 years, and 40 [18.0%] at 5 years) (P = .02). In addition, the all-cause mortality event rates were significantly higher among patients with BAV with raphe (77 [5.1%] at 1 year, 87 [6.2%] at 2 years, and 110 [9.5%] at 5 years) vs patients without raphe (2 [1.8%] at 1 year, 3 [3.0%] at 2 years, and 5 [4.4%] at 5 years) (P = .03). However, on multivariable analysis, the presence of raphe was not significantly associated with all-cause mortality. In this large multicenter, international BAV registry, the presence of raphe was associated with a higher prevalence of significant aortic stenosis and regurgitation. The presence of raphe was also associated with increased rates of aortic valve and aortic surgery. Although patients with BAV and raphe had higher mortality rates than patients without, the presence of a raphe was not independently associated with increased all-cause mortality.

Effect of combined endurance-resistance training and soy extract supplementation on expression of eNOS gene in ovariectomized rats

PubMed Central

Ravasi, Ali Asghar

2017-01-01

Introduction Menopause is an independent risk factor for cardiovascular disease (CVD). Physical exercise and soybean diets have been suggested to reduce the risk of CVD in postmenopausal women. The purpose of this study was to investigate the effects of combined resistance and endurance (RE) training and soy extract (SOY) supplementation, both known to improve endothelial function, on expression of the eNOS gene in the heart of ovariectomized (OVX) rats. Material and methods Fifty female Wistar rats were divided into five groups: 1) sham (SHAM); 2) ovariectomy (OVX); 3) ovariectomy with soy extract supplementation (OVX + SOY); 4) OVX with RE training (OVX + RE); 5) and ovariectomy plus RE training with soy extract supplementation (OVX + RE + SOY). RE training and soy extract supplementation were administered alone or in combination for 6 weeks. The effects of these treatments on cardiac eNOS expression were measured using real-time PCR. Results Ovariectomy down-regulated cardiac eNOS gene expression; however, 6 weeks of SOY treatment or RE training reversed this effect (p ≤ 0.05). The combination of SOY plus RE was greater than RE or SOY alone in reversing estrogen-deficiency-caused eNOS down-regulation (p ≤ 0.05). Conclusions Our data suggest that the combinatory regimen of soy extract supplementation and regular RE training may be more beneficial to cardiovascular disease risk in a menopause rat model than either exercise or soy supplementation alone. PMID:29242848

Development of confocal immunofluorescence FRET microscopy to Investigate eNOS and GSNOR localization and interaction in pulmonary endothelial cells

NASA Astrophysics Data System (ADS)

Rehman, Shagufta; Brown-Steinke, Kathleen; Palmer, Lisa; Periasamy, Ammasi

2015-03-01

Confocal FRET microscopy is a widely used technique for studying protein-protein interactions in live or fixed cells. Endothelial nitric oxide synthase (eNOS) and S-nitrosoglutathione reductase (GSNOR) are enzymes involved in regulating the bioavailability of S-nitrosothiols (SNOs) in the pulmonary endothelium and have roles in the development of pulmonary arterial hypertension. Labeling of endogenous proteins to better understand a disease process can be challenging. We have used immunofluorescence to detect endogenous eNOS and GSNOR in primary pulmonary endothelial cells to co-localize these proteins as well as to study their interaction by FRET. The challenge has been in selecting the right immunofluorescence labeling condition, right antibody, the right blocking reagent, the right FRET pair and eliminating cross-reactivity of secondary antibodies. We have used Alexa488 and Alexa568 as a FRET pair. After a series of optimizations, the data from Confocal Laser Scanning Microscopy (CLSM) demonstrate co-localization of eNOS and GSNOR in the perinuclear region of the pulmonary endothelial cell primarily within the cis-Golgi with lower levels of co-localization seen within the trans-Golgi. FRET studies demonstrate, for the first time, interaction between eNOS and GSNOR in both murine and bovine pulmonary endothelial cells. Further characterization of eNOSGSNOR interaction and the subcellular location of this interaction will provide mechanistic insight into the importance of S-nitrosothiol signaling in pulmonary biology, physiology and pathology.

A meta-analysis of aortic root size in elite athletes.

PubMed

Iskandar, Aline; Thompson, Paul D

2013-02-19

The aorta is exposed to hemodynamic stress during exercise, but whether or not the aorta is larger in athletes is not clear. We performed a systematic literature review and meta-analysis to examine whethere athletes demonstrate increased aortic root dimensions compared with nonathlete controls. We searched MEDLINE and Scopus from inception through August 12, 2012, for English-language studies reporting the aortic root size in elite athletes. Two investigators independently extracted athlete and study characteristics. A multivariate linear mixed model was used to conduct meta-regression analyses. We identified 71 studies reporting aortic root dimensions in 8564 unique athletes, but only 23 of these studies met our criteria by reporting aortic root dimensions at the aortic valve annulus or sinus of Valsalva in elite athletes (n=5580). Athletes were compared directly with controls (n=727) in 13 studies. On meta-regression, the weighted mean aortic root diameter measured at the sinuses of Valsalva was 3.2 mm (P=0.02) larger in athletes than in the nonathletic controls, whereas aortic root size at the aortic valve annulus was 1.6 mm (P=0.04) greater in athletes than in controls. Elite athletes have a small but significantly larger aortic root diameter at the sinuses of Valsalva and aortic valve annulus, but this difference is minor and clinically insignificant. Clinicians evaluating athletes should know that marked aortic root dilatation likely represents a pathological process and not a physiological adaptation to exercise.

Aortic Valve Replacement for Moderate Aortic Stenosis with Severe Calcification and Left Ventricualr Dysfunction-A Case Report and Review of the Literature.

PubMed

Narang, Nikhil; Lang, Roberto M; Liarski, Vladimir M; Jeevanandam, Valluvan; Hofmann Bowman, Marion A

2017-01-01

A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis. Guideline directed medical therapy for heart failure with reduced EF was initiated; however, diuretics and neurohormonal blockade (beta-blocker and angiotensin receptor blocker) provided minimal improvement, and the patient remained functionally limited. Of interest, echocardiography performed 1 year prior to his presentation showed normal LV EF and mild aortic leaflet calcification with moderate stenosis, suggesting a rapid progressing of calcific aortic valve disease. Subsequently, the patient underwent surgical aortic valve replacement and demonstrated excellent postsurgical recovery of LV EF (55%). Calcific aortic valve disease is commonly associated with aging, bicuspid aortic valve, and chronic kidney disease. Pathophysiological mechanism for valvular calcification is incompletely understood but include osteogenic transformation of valvular interstitial cells mediated by local and systemic inflammatory processes. Several rheumatologic diseases including RA are associated with premature atherosclerosis and arterial calcification, and we speculated a similar role of RA accelerating calcific aortic valve disease. We present a case of accelerated aortic valve calcification with (only) moderate stenosis, complicated by a rapid decline in LV systolic performance. Guidelines for AVR in moderate stenosis without concomitant cardiac surgery are not well established, although it should be

Increasing the feasibility of minimally invasive procedures in type A aortic dissections: a framework for segmentation and quantification.

PubMed

Morariu, Cosmin Adrian; Terheiden, Tobias; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Pauli, Josef

2016-02-01

Our goal is to provide precise measurements of the aortic dimensions in case of dissection pathologies. Quantification of surface lengths and aortic radii/diameters together with the visualization of the dissection membrane represents crucial prerequisites for enabling minimally invasive treatment of type A dissections, which always also imply the ascending aorta. We seek a measure invariant to luminance and contrast for aortic outer wall segmentation. Therefore, we propose a 2D graph-based approach using phase congruency combined with additional features. Phase congruency is extended to 3D by designing a novel conic directional filter and adding a lowpass component to the 3D Log-Gabor filterbank for extracting the fine dissection membrane, which separates the true lumen from the false one within the aorta. The result of the outer wall segmentation is compared with manually annotated axial slices belonging to 11 CTA datasets. Quantitative assessment of our novel 2D/3D membrane extraction algorithms has been obtained for 10 datasets and reveals subvoxel accuracy in all cases. Aortic inner and outer surface lengths, determined within 2 cadaveric CT datasets, are validated against manual measurements performed by a vascular surgeon on excised aortas of the body donors. This contribution proposes a complete pipeline for segmentation and quantification of aortic dissections. Validation against ground truth of the 3D contour lengths quantification represents a significant step toward custom-designed stent-grafts.

Vascular structure and oxidative stress in salt-loaded spontaneously hypertensive rats: effects of losartan and atenolol.

PubMed

de Cavanagh, Elena M V; Ferder, León F; Ferder, Marcelo D; Stella, Inés Y; Toblli, Jorge E; Inserra, Felipe

2010-12-01

Renin-angiotensin system (RAS) modulation by high dietary sodium may contribute to salt-induced hypertension, oxidative stress, and target organ damage. We investigated whether angiotensin II (Ang-II) type 1 (AT1)-receptor blockade (losartan) could protect the aorta and renal arteries from combined hypertension- and high dietary salt-related oxidative stress. Spontaneously hypertensive rats (3-month-old, n = 10/group) received tap water (SHR), water containing 1.5% NaCl (SHR+S), 1.5% NaCl and 30 mg losartan/kg/day (SHR+S+L), or 50 mg atenolol/kg/day (SHR+S+A). Atenolol was used for comparison. Ten Wistar-Kyoto rats (WKY) were controls. Systolic blood pressure (SBP) was determined by tail plethysmography. After 5 months of treatment, vascular remodeling and oxidative stress (superoxide production and NAD(P)H-oxidase activity (chemiluminescence), malondialdehyde (MDA) content (high-performance liquid chromatography), endothelial nitric oxide synthase (eNOS) activity [(14)C-arginine to (14)C citrulline], CuZn-SOD activity (spectrophotometry)) were studied. In SHR, salt-loading significantly aggravated hypertension, urinary protein excretion, intraparenchymal renal artery (IPRArt) perivascular fibrosis, aortic and renal artery oxidative stress, and induced endothelial cell loss in IPRArts. In salt-loaded SHR, 5-month losartan and atenolol treatments similarly reduced SBP, but only losartan significantly prevented (i) urinary protein excretion increase, (ii) or attenuated hypertension-related vascular remodeling, (iii) aortic MDA accumulation, (iv) renal artery eNOS activity lowering, and (v) aortic and renal artery superoxide dismutase (SOD) activity reduction. In SHR+S, the contributions to aortic superoxide production were as follows: uncoupled eNOS > xanthine oxidase (XO) > NAD(P)H oxidase. In this salt-sensitive genetic hypertension model, losartan protects from hypertension- and high dietary salt-related vascular oxidative stress, exceeding the benefits of BP

Minimally Invasive Aortic Valve Replacement Following Root Enlargement on too Narrow Annulus to Perform Transcatheter Aortic Valve Implantation.

PubMed

Sakamoto, Kosuke; Totsugawa, Toshinori; Hiraoka, Arudo; Tamura, Kentaro; Yoshitaka, Hidenori; Sakaguchi, Taichi

2018-05-30

An 88-year-old woman was diagnosed with aortic stenosis and an aortic annulus that was too narrow to perform transcatheter aortic valve implantation. Surgery was performed through a 7-cm right mini-thoracotomy at the fourth intercostal space. A 19-mm aortic valve bioprosthesis was implanted after root enlargement. The fourth intercostal space was a suitable site for aortic root enlargement because of the shorter skin-to-root distance and the detailed exposure of the aortic valve after cutting the aortic wall. This study concluded that minimally-invasive aortic valve replacement following root enlargement can be an option for the treatment of elderly patients with aortic stenosis accompanied by an annulus that is too small to perform transcatheter aortic valve implantation.

Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm.

PubMed

O'Neil, C R; Taylor, G; Smith, S; Joffe, A M; Antonation, K; Shafran, S; Kunimoto, D

2018-02-01

We present a case of Mycobacterium chimaera infection presenting with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians should consider M. chimaera infection in those presenting with aortic dissection as a late complication of cardiovascular surgery.

Unusual Case of Overt Aortic Dissection Mimicking Aortic Intramural Hematoma

PubMed Central

Disha, Kushtrim; Kuntze, Thomas; Girdauskas, Evaldas

2016-01-01

We report an interesting case in which overt aortic dissection mimicked two episodes of aortic intramural hematoma (IMH) (Stanford A, DeBakey I). This took place over the course of four days and had a major influence on the surgical treatment strategy. The first episode of IMH regressed completely within 15 hours after it was clinically diagnosed and verified using imaging techniques. The recurrence of IMH was detected three days thereafter, resulting in an urgent surgical intervention. Overt aortic dissection with evidence of an intimal tear was diagnosed intraoperatively. PMID:27066437

[Transcatheter aortic valve replacement].

PubMed

Sawa, Yoshiki

2014-07-01

While transcatheter aortic valve replacement( TAVR) has spread rapidly all over the world for highrisk patients with severe aortic stenosis (AS), SAPIEN XT was approved in Japan in October 2013. Since that, approximately 400 TAVR cases were performed in Japan. In our institute, we have performed 164 cases since first case in Japan in 2009 and have achieved satisfactory early results(30-day mortality:1.2%). At the same time, however, simultaneously various TAVR-related complications including a paravalvular leak, stroke, vascular complications, and coronary obstruction were observed. A reduction in the incidence and severity of these complications had led technical improvements in various new devices(2nd generation TAVR device such as the SAPIEN 3, ACURATE, and JenaValve) and in implantation techniques including repositioning/recapturing features, paravalvular sealing technologies, and prevention of coronary obstruction. Furthermore, there is also increasing experience with special indications for TAVR such as pure aortic valve insufficiency or valve-in-valve techniques. Currently, an increasing number of publications of midterm results demonstrate good prosthetic valve function and durability, with good quality of life and low morbidity after TAVR. There are also some randomized trials such as PARTNER 2 or SURTAVI to investigate potential benefits of TAVR for intermediate-risk patients. These improvements in the TAVR devices promises the expansion of TAVR towards the treatment of lower-risk patients in the near future.

Eight-year results of aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis.

PubMed

Kon, Neal D; Riley, Robert D; Adair, Sandy M; Kitzman, Dalane W; Cordell, A Robert

2002-06-01

Stentless porcine aortic valves offer several advantages over traditional valves. Among these are superior hemodynamics, laminar flow patterns, lack of need for anticoagulation, and perhaps improved durability. One hundred four patients were operated on from September 17, 1992, to October 31, 1997, as part of a multicenter worldwide investigation of the Medtronic Freestyle stentless porcine bioprosthesis. All patients received a total aortic root replacement. The patients were evaluated postoperatively at discharge, at 3 to 6 months, and yearly by clinical examination and color flow Doppler echocardiography. Operative mortality was 3.9%. No patient experienced structural valve deterioration, nonstructural deterioration, perivalvular leak, or unacceptable hemodynamic performance. At 8 years, survival was 59.8%. Freedom from thromboembolic complications was 83.3%. Freedom from postoperative endocarditis was 96.9%. Freedom from reoperation was 100%. Mean systolic gradients did not change over the time period studied. They were 6.4 +/- 3.8 mm Hg at 1 year and 6.7 +/- 2.6 mm Hg at 8 years. Correspondingly, effective orifice area was 1.9 +/- 0.7 cm2 at 1 year and 1.8 +/- 0.8 cm2 at 8 years. The incidence of any aortic insufficiency also did not change over the length of follow-up. At 1 year, 98% of patients had no or trivial aortic insufficiency and 2% had mild aortic insufficiency. At 8 years, 100% of patients evaluated were free of any aortic insufficiency. The Medtronic Freestyle aortic root bioprosthesis can be used safely to replace the aortic root or aortic valve for aortic valve and aortic root pathology. Total root replacement allows optimal hemodynamic performance with no significant aortic regurgitation. Results up to 8 years show excellent survival and no signs of degeneration. Further follow-up is still needed to determine valve durability.

Treatment of aortic stenosis with aortic valve bypass (apicoaortic conduit) surgery: an assessment using computational modeling.

PubMed

Balaras, Elias; Cha, K S; Griffith, Bartley P; Gammie, James S

2009-03-01

Aortic valve bypass surgery treats aortic valve stenosis with a valve-containing conduit that connects the left ventricular apex to the descending thoracic aorta. After aortic valve bypass, blood is ejected from the left ventricle via both the native stenotic aortic valve and the conduit. We performed computational modeling to determine the effects of aortic valve bypass on aortic and cerebral blood flow, as well as the effect of conduit size on relative blood flow through the conduit and the native valve. The interaction of blood flow with the vascular boundary was modeled using a hybrid Eurelian-Lagrangian formulation, where an unstructured Galerkin finite element method was coupled with an immersed boundary approach. Our model predicted native (stenotic) valve to conduit flow ratios of 45:55, 52:48, and 60:40 for conduits with diameters of 20, 16, and 10 mm, respectively. Mean gradients across the native aortic valve were calculated to be 12.5, 13.8, and 17.6 mm Hg, respectively. Post-aortic valve bypass cerebral blood flow was unchanged from preoperative aortic valve stenosis configurations and was constant across all conduit sizes. In all cases modeled, cerebral blood flow was completely supplied by blood ejected across the native aortic valve. An aortic valve bypass conduit as small as 10 mm results in excellent relief of left ventricular outflow tract obstruction in critical aortic valve stenosis. The presence of an aortic valve bypass conduit has no effect on cerebral blood flow. All blood flow to the brain occurs via antegrade flow across the native stenotic valve; this configuration may decrease the long-term risk of cerebral thromboembolism.

Abdominal aortic atherosclerosis at MR imaging is associated with cardiovascular events: the Dallas heart study.

PubMed

Maroules, Christopher D; Rosero, Eric; Ayers, Colby; Peshock, Ronald M; Khera, Amit

2013-10-01

To determine the value of two abdominal aortic atherosclerosis measurements at magnetic resonance (MR) imaging for predicting future cardiovascular events. This study was approved by the institutional review board and complied with HIPAA regulations. The study consisted of 2122 participants from the multiethnic, population-based Dallas Heart Study who underwent abdominal aortic MR imaging at 1.5 T. Aortic atherosclerosis was measured by quantifying mean aortic wall thickness (MAWT) and aortic plaque burden. Participants were monitored for cardiovascular death, nonfatal cardiac events, and nonfatal extracardiac vascular events over a mean period of 7.8 years ± 1.5 (standard deviation [SD]). Cox proportional hazards regression was used to assess independent associations of aortic atherosclerosis and cardiovascular events. Increasing MAWT was positively associated with male sex (odds ratio, 3.66; P < .0001), current smoking (odds ratio, 2.53; P < .0001), 10-year increase in age (odds ratio, 2.24; P < .0001), and hypertension (odds ratio, 1.66; P = .0001). A total of 143 participants (6.7%) experienced a cardiovascular event. MAWT conferred an increased risk for composite events (hazard ratio, 1.28 per 1 SD; P = .001). Aortic plaque was not associated with increased risk for composite events. Increasing MAWT and aortic plaque burden both conferred an increased risk for nonfatal extracardiac events (hazard ratio of 1.52 per 1 SD [P < .001] and hazard ratio of 1.46 per 1 SD [P = .03], respectively). MR imaging measures of aortic atherosclerosis are predictive of future adverse cardiovascular events. © RSNA, 2013.

Cocaine Exposure Increases Blood Pressure and Aortic Stiffness via the miR-30c-5p-Malic Enzyme 1-Reactive Oxygen Species Pathway.

PubMed

Zhu, Wei; Wang, Huilan; Wei, Jianqin; Sartor, Gregory C; Bao, Michelle Meiqi; Pierce, Clay T; Wahlestedt, Claes R; Dykxhoorn, Derek M; Dong, Chunming

2018-04-01

Cocaine abuse increases the risk of cardiovascular mortality and morbidity; however, the underlying molecular mechanisms remain elusive. By using a mouse model for cocaine abuse/use, we found that repeated cocaine injection led to increased blood pressure and aortic stiffness in mice associated with elevated levels of reactive oxygen species (ROS) in the aortas, a phenomenon similar to that observed in hypertensive humans. This ROS elevation was correlated with downregulation of Me1 (malic enzyme 1), an important redox molecule that counteracts ROS generation, and upregulation of microRNA (miR)-30c-5p that targets Me1 expression by directly binding to its 3'UTR (untranslated region). Remarkably, lentivirus-mediated overexpression of miR-30c-5p in aortic smooth muscle cells recapitulated the effect of cocaine on Me1 suppression, which in turn led to ROS elevation. Moreover, in vivo silencing of miR-30c-5p in smooth muscle cells resulted in Me1 upregulation, ROS reduction, and significantly suppressed cocaine-induced increases in blood pressure and aortic stiffness-a similar effect to that produced by treatment with the antioxidant N-acetyl cysteine. Discovery of this novel cocaine-↑miR-30c-5p-↓Me1-↑ROS pathway provides a potential new therapeutic avenue for treatment of cocaine abuse-related cardiovascular disease. © 2018 American Heart Association, Inc.

Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

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

Chen, I-Ming; Chen, Po-Lin; Huang, Chun-Yang

PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the completemore » regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.« less

Differential response of endothelial cells to simvastatin when conditioned with steady, non-reversing pulsatile or oscillating shear stress.

PubMed

Rossi, Joanna; Jonak, Paul; Rouleau, Leonie; Danielczak, Lisa; Tardif, Jean-Claude; Leask, Richard L

2011-01-01

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 μM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 μM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 μM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 μM. A higher simvastatin concentration of 10 μM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.

Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort.

PubMed

Lindman, Brian R; Maniar, Hersh S; Jaber, Wael A; Lerakis, Stamatios; Mack, Michael J; Suri, Rakesh M; Thourani, Vinod H; Babaliaros, Vasilis; Kereiakes, Dean J; Whisenant, Brian; Miller, D Craig; Tuzcu, E Murat; Svensson, Lars G; Xu, Ke; Doshi, Darshan; Leon, Martin B; Zajarias, Alan

2015-04-01

Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether

Abdominal aortic aneurysm

MedlinePlus

... this problem include: Smoking High blood pressure Male gender Genetic factors An abdominal aortic aneurysm is most ... body from an aortic aneurysm, you will need surgery right away. If the aneurysm is small and ...

The impact of the metabolic syndrome on the outcome after aortic valve replacement.

PubMed

Tadic, Marijana; Vukadinovic, Davor; Cvijanovic, Dane; Celic, Vera; Kocica, Mladen; Putnik, Svetozar; Ivanovic, Branislava

2014-10-01

The aim of this study was to examine the influence of the metabolic syndrome on the left ventricular geometry as well as on the early and mid-time outcome in patients with aortic stenosis who underwent aortic valve replacement. The study included 182 patients who underwent aortic valve replacement due to aortic stenosis. The metabolic syndrome was defined by the presence of at least three AHA-NHLB (American Heart Association/National Heart, Lung and Blood Institute) criteria. All the patients were followed for at least 2 years after the surgery. The metabolic syndrome did not influence the severity of aortic stenosis (mean gradient and aortic valve area). However, the metabolic syndrome was associated with the reduced prevalence of the normal left ventricular geometry and the increased risk of concentric left ventricular hypertrophy in patients with aortic stenosis. Among the metabolic syndrome criteria, only increased blood pressure was simultaneously associated with the short-term and mid-term outcome, independently of other risk factors. Increased fasting glucose level was an independent predictor of the only 30-day outcome after the valve replacement. The metabolic syndrome and left ventricular hypertrophy were, independently of hypertension and diabetes, associated with the 30-day outcome, as well as incidence of major cerebrovascular and cardiovascular events in the 2-year postoperative period. The metabolic syndrome does not change severity of the aortic stenosis, but significantly impacts the left ventricular remodeling in these patients. The metabolic syndrome and left ventricular hypertrophy, irrespective of hypertension and diabetes, are predictors of the short-term and mid-term outcome of patients with aortic stenosis who underwent aortic valve replacement.

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

ClinicalTrials.gov

2018-02-19

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome

Potential role of eNOS in the therapeutic control of myocardial oxygen consumption by ACE inhibitors and amlodipine.

PubMed

Loke, K E; Messina, E J; Shesely, E G; Kaley, G; Hintze, T H

2001-01-01

Our aim was to investigate the potential therapeutic role of endothelial nitric oxide synthase (eNOS) in the modulation of cardiac O(2) consumption induced by the angiotensin converting enzyme (ACE) inhibitor ramiprilat and amlodipine. Three different groups of mice were used; wild type, wild type in the presence of N-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or genetically altered mice lacking the eNOS gene (eNOS -/-). Myocardial O(2) consumption was measured using a Clark-type O(2) electrode in an air-tight stirred bath. Concentration-response curves to ramiprilat (RAM), amlodipine (AMLO), diltiazem (DIL), carbachol (CCL), substance P (SP) and S-nitroso-N-acetyl-penicillamine (SNAP) were performed. The rate of decrease in O(2) concentration was expressed as a percentage of the baseline. Baseline O(2) consumption was not different between the three groups of mice. In tissues from wild type mice, RAM (10(-5) mol/l), AMLO (10(-5) mol/l), DIL (10(-4) mol/l), CCL (10(-4) mol/l), SP (10(-7) mol/l) and SNAP (10(-4) mol/l) reduced myocardial O(2) consumption by -32+/-4, -27+/-10, -20+/-6, -25+/-2, -22+/-4 and -42+/-4%, respectively. The responses to RAM, AMLO, CCL and SP were absent in tissues taken from eNOS -/- mice (-7.1+/-4.3, -5.0+/-6.0, -5.2+/-5.1 and -0.4+/-0.2%, respectively). In addition, L-NAME significantly (P<0.05) inhibited the reduction in O(2) consumption induced by RAM (-9.8+/-4.4%), AMLO (-1.0+/-6.0%), CCL (-8.8+/-3.7%) and SP (-6.6+/-4.9%) in cardiac tissues from wild type mice. In contrast, NO-independent responses to the calcium channel antagonist, DIL, and responses to the NO donor, SNAP, were not affected in cardiac tissues taken from eNOS -/- (DIL: -20+/-4%; SNAP: -46+/-6%) or L-NAME-treated (DIL: -17+/-2%; SNAP: -33+/-5%) mice. These results suggest that endogenous endothelial NO synthase derived NO serves an important role in the regulation of myocardial O(2) consumption. This action may contribute to the therapeutic action of ACE

Transapical aortic valve implantation and minimally invasive off-pump bypass surgery

PubMed Central

Ahad, Samir; Baumbach, Hardy; Hill, Stephan; Franke, Ulrich F. W.

2014-01-01

Transcatheter aortic valve implantation (TAVI) has gained increasing popularity for high-risk patients with symptomatic aortic valve stenosis. A concomitant coronary artery disease leads to a complicated management and an increased perioperative risk. This case report describes the successful total arterial coronary revascularization of the left anterior descending and the left marginal branch of the circumflex artery utilizing the left internal mammary artery (LIMA) and left radial artery in off-pump technique in combination with the transapical transcatheter aortic valve implantation via minimally invasive anterolateral access in the fifth intercostal space. PMID:24221960

Comment to 'Regarding "Diabetes mellitus increases the risk of ruptured abdominal aortic aneurysms"'.

PubMed

Wierzba, Waldemar; Sliwczynski, Andrzej; Pinkas, Jaroslaw; Jawien, Arkadiusz; Karnafel, Waldemar

2018-01-01

This publication is a commentary on the Letter to the Editor by Juliette Raffort and Fabien Lareyre. This article clarifies a number of concerns about the method of calculating the index of prevalence of ruptured abdominal aortic aneurysms (AAA). The method of qualifying patients for the study and the method of calculating the index of prevalence of ruptured AAA in cohorts of diabetic and non-diabetic patients was presented. Most researchers calculate the Index of Prevalence per 100,000 of the general population. This gives the misleading result that diabetes reduces the risk of AAA rupture.We used a method which calculated prevalence per 100,000 with diabetes mellitus and per 100,000 without diabetes mellitus. This method confirms that diabetes mellitus increases the risk of ruptured AAA.

Unusual cause of central aortic prosthetic regurgitation during transcatheter replacement.

PubMed

López-Mínguez, José Ramón; Millán-Núñez, Victoria; González-Fernández, Reyes; Nogales-Asensio, Juan Manuel; Fuentes-Cañamero, María Eugenia; Merchán-Herrera, Antonio

2016-04-01

Transcatheter aortic valve replacement (TAVR) is an increasingly common procedure for the treatment of aortic stenosis in elderly patients with comorbidities that prevent the use of standard surgery. It has been shown that implantation without aortic regurgitation is related to lower mortality. Mild paravalvular regurgitation is inevitable in some cases due to calcification of the aortic annulus and its usually somewhat elliptical shape. Central regurgitation is less common, but has been associated with valve overdilatation in cases in which reduction of paravalvular regurgitation was attempted after the initial inflation. However, there are no reported cases of central prosthetic aortic regurgitation due to acute LV dysfunction. We report a case in which central aortic regurgitation occurred due to transient ventricular dysfunction secondary to occlusion of the right coronary artery by an embolus. The regurgitation disappeared after thrombus aspiration and normal ventricular function was immediately recovered. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B Aortic Dissection with Severe Limb Ischemia.

PubMed

Higuchi, Yoshiro; Tochii, Masato; Takami, Yoshiyuki; Kobayashi, Akihiro; Yanagisawa, Tsutomu; Amano, Kentaro; Sakurai, Yusuke; Ishida, Michiko; Ishikawa, Hiroshi; Hattori, Koji; Takagi, Yasushi

2017-03-24

We report a rare case of retrograde Stanford type A aortic dissection after endovascular repair for complicated Stanford type B aortic dissection. A 45-year-old man presented with a sudden onset of back pain and was transferred to our hospital. Computed tomography demonstrated acute Stanford type B aortic dissection with lower limb ischemia. Emergency endovascular surgery was planned for repair of the Stanford type B aortic dissection. The patient suddenly developed recurrent chest pain 10 days after the initial procedure. Computed tomography revealed retrograde Stanford type A aortic dissection involving the ascending aorta and aortic arch. The patient underwent a successful emergency total aortic arch replacement.

Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors.

PubMed

Lau, Eva On-Chai; Lo, Chun-Yin; Yao, Yifei; Mak, Arthur Fuk-Tat; Jiang, Liwen; Huang, Yu; Yao, Xiaoqiang

2016-01-01

Arterial baroreceptors are mechanical sensors that detect blood pressure changes. It has long been suggested that the two arterial baroreceptors, aortic and carotid baroreceptors, have different pressure sensitivities. However, there is no consensus as to which of the arterial baroreceptors are more sensitive to changes in blood pressure. In the present study, we employed independent methods to compare the pressure sensitivity of the two arterial baroreceptors. Firstly, pressure-activated action potential firing was measured by whole-cell current clamp with a high-speed pressure clamp system in primary cultured baroreceptor neurons. The results show that aortic depressor neurons possessed a higher percentage of mechano-sensitive neurons. Furthermore, aortic baroreceptor neurons show a lower pressure threshold than that of carotid baroreceptor neurons. Secondly, uniaxial stretching of baroreceptor neurons, that mimics the forces exerted on blood vessels, elicited a larger increase in intracellular Ca(2+) rise in aortic baroreceptor neurons than in carotid baroreceptor neurons. Thirdly, the pressure-induced action potential firing in the aortic depressor nerve recorded in vivo was also higher. The present study therefore provides for a basic physiological understanding on the pressure sensitivity of the two baroreceptor neurons and suggests that aortic baroreceptors have a higher pressure sensitivity than carotid baroreceptors.

Spinal cord protection in descending thoracic and thoracoabdominal aortic aneurysm repair.

PubMed

Safi, H J; Campbell, M P; Ferreira, M L; Azizzadeh, A; Miller, C C

1998-01-01

During aneurysm repair of the descending thoracic or thoracoabdominal aorta, the likelihood of neurological complications increases greatly after only 30 minutes of spinal cord ischemia. However, the manifestation of paraplegia or paraparesis relates not only to aortic cross-clamping time, but to multiple factors that may include aortic dissection, previous aortic surgery, advanced age, preoperative renal insufficiency, rupture, and most significantly, aneurysm extent. At greatest risk is the patient with type II thoracoabdominal aortic aneurysm. For this patient the simple cross-clamp technique, which uses no protective surgical adjuncts, heightens the threat of neurological deficit. With the surgical adjuncts of cerebrospinal fluid drainage and distal aortic perfusion, the probability of neurological deficit is appreciably lowered.

Maximal aortic diameter affects outcome after endovascular repair of abdominal aortic aneurysms.

PubMed

Huang, Ying; Gloviczki, Peter; Duncan, Audra A; Kalra, Manju; Oderich, Gustavo S; Fleming, Mark D; Harmsen, William S; Bower, Thomas C

2017-05-01

The purpose of this study was to evaluate whether maximal aortic diameter affects outcome after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA). Clinical data of patients undergoing EVAR between 1997 and 2011 for nonruptured asymptomatic AAAs in a tertiary center were reviewed. Patients were classified according to diameter of AAA: group 1, <5.0 cm; group 2, 5.0 to 5.4 cm; group 3, 5.5 to 5.9 cm; and group 4, ≥6.0 cm. The primary end point was all-cause mortality; secondary end points were complications, reinterventions, and ruptures. There were 874 patients studied (female, 108 [12%]; group 1, 119; group 2, 246; group 3, 243; group 4, 266); mean age was 76 ± 7.2 years. The 30-day mortality rate was 1.0%, not significantly different between groups (P = .22); complication and reintervention rates were 13% and 4.1%, respectively, similar between groups (P < .05). Five-year survival was 68%; freedom from complications and reinterventions was 65% and 74%, respectively; rupture rate was 0.5%. Multivariate analysis revealed that factors associated with all-cause mortality included maximal aortic diameter, age, gender, surgical risk, cancer history, and endograft type (P < .05). Group 4 had increased risks of mortality (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.38-2.85; P = .002) and complications (HR, 1.6; 95% CI, 1.2-2.7; P = .009) relative to group 1. Reinterventions were more frequent for aneurysms ≥6.0 cm (HR, 2.0; 95% CI, 1.2-3.3; P = .01). Late rupture rate after EVAR was not different between groups. Maximal aortic diameter is associated with long-term outcomes after elective EVAR. Patients with large AAAs (≥6.0 cm) have higher all-cause mortality, complication, and reintervention rates after EVAR than those with smaller aneurysms. We continue to recommend that AAAs be repaired when they reach 5.5 cm as recommended by the guidelines of the Society for Vascular Surgery. On the basis of our data, EVAR

Women with TT genotype for eNOS gene are more responsive in lowering blood pressure in response to exercise.

PubMed

Sponton, Carlos H G; Rezende, Tiago M; Mallagrino, Pamella A; Franco-Penteado, Carla F; Bezerra, Marcos André C; Zanesco, Angelina

2010-12-01

The aim of this study was to investigate whether -786T>C endothelial nitric oxide synthase (eNOS) gene polymorphism might influence the effect of long-term exercise training (ET) on the blood pressure and its relationship with NO production in healthy postmenopausal women. Longitudinal study. Fifty-five postmenopausal women were studied in a double-blinded design. ET was performed for 3 days a week, each session consisting of 60 min during 6 months, in an intensity of 50-70% VO2max. After that, eNOS genotype analysis was performed and women were divided into two groups: TC+CC (n=41) and TT (n=14) genotype. No changes were found in the anthropometric parameters after ET in both the groups. Systolic and diastolic BP values were significantly reduced in both the groups, but women with TT genotype were more responsive in lowering BP as compared with those with TC+CC genotype. Plasma nitrite/nitrate concentrations were similar at baseline in both the groups, but the magnitude of increment in NO production in response to ET was higher in women with TT genotype as compared with those with TC+CC genotype. Our study shows clearly that women with or without eNOS gene polymorphism had no differences in NO production at basal conditions, but when physical exercise is applied an evident difference is detected showing that the presence of -786T>C eNOS gene polymorphism had a significant impact in the health-promoting effect of aerobic physical training on the blood pressure in postmenopausal women.

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

PubMed

Nagy, Christian D; Alejo, Diane E; Corretti, Mary C; Ravekes, William J; Crosson, Jane E; Spevak, Philip J; Ringel, Richard; Carson, Kathryn A; Khalil, Sara; Dietz, Harry C; Cameron, Duke E; Vricella, Luca A; Traill, Thomas A; Holmes, Kathryn W

2013-04-01

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Transcatheter aortic valve insertion (TAVI): a review

PubMed Central

Morgan-Hughes, G; Roobottom, C

2014-01-01

The introduction of transcatheter aortic valve insertion (TAVI) has transformed the care provided for patients with severe aortic stenosis. The uptake of this procedure is increasing rapidly, and clinicians from all disciplines are likely to increasingly encounter patients being assessed for or having undergone this intervention. Successful TAVI heavily relies on careful and comprehensive imaging assessment, before, during and after the procedure, using a range of modalities. This review outlines the background and development of TAVI, describes the nature of the procedure and considers the contribution of imaging techniques, both to successful intervention and to potential complications. PMID:24258463

Thoracic aortic aneurysm clinically pertinent controversies and uncertainties.

PubMed

Elefteriades, John A; Farkas, Emily A

2010-03-02

This paper addresses clinical controversies and uncertainties regarding thoracic aortic aneurysm and its treatment. 1) Estimating true aortic size is confounded by obliquity, asymmetry, and noncorresponding sites: both echocardiography and computed tomography/magnetic resonance imaging are necessary for complete assessment. 2) Epidemiology of thoracic aortic aneurysm. There has been a bona fide increase in incidence of aortic aneurysm making aneurysm disease the 18th most common cause of death. 3) Aortic growth rate. Although a virulent disease, thoracic aortic aneurysm is an indolent process. The thoracic aorta grows slowly-0.1 cm/year. 4) Evidence-based intervention criteria. It is imperative to extirpate the thoracic aorta before rupture or dissection occurs; surgery at 5.0- to 5.5-cm diameter will prevent most adverse natural events. Symptomatic (painful) aneurysms must be resected regardless of size. 5) Development of nonsize criteria. Mechanical properties of the aorta deteriorate at the same 6 cm at which dissection occurs; elastic properties of the aorta may soon become useful intervention criteria. 6) Medical treatment of aortic aneurysm. Medical treatment is of unproven value, even beta-blockers and angiotensin-receptor blockers. 7) A genetic disease. Even non-Marfan aneurysms have a strong genetic basis. 8) Need for biomarkers. Virulent but silent, TAA cries out for a biomarker that can predict the onset of adverse events. Pathophysiologic understanding has led to identification of promising biomarkers, especially metalloproteinases. 9) Endovascular therapy for aneurysms. Endovascular therapy has burgeoned, despite the fact that the EVAR-2, DREAM, and INSTEAD trials showed no benefit at mid-term over medical or conventional surgical therapy. We must avoid "irrational exuberance." 10) Inciting events for acute aortic dissection. Recent evidence shows that dissections are preceded by a specific severe exertional or emotional event. 11) "Silver lining" of

Stroke Volume estimation using aortic pressure measurements and aortic cross sectional area: Proof of concept.

PubMed

Kamoi, S; Pretty, C G; Chiew, Y S; Pironet, A; Davidson, S; Desaive, T; Shaw, G M; Chase, J G

2015-08-01

Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV.

[Transcatheter aortic valve implantation for aortic stenosis. Initial experience].

PubMed

Careaga-Reyna, Guillermo; Lázaro-Castillo, José Luis; Lezama-Urtecho, Carlos Alberto; Macías-Miranda, Enriqueta; Dosta-Herrera, Juan José; Galván Díaz, José

Aortic stenosis is a frequent disease in the elderly, and is associated with other systemic pathologies that may contraindicate the surgical procedure. Another option for these patients is percutaneous aortic valve implantation, which is less invasive. We present our initial experience with this procedure. Patients with aortic stenosis were included once selection criteria were accomplished. Under general anaesthesia and echocardiographic and fluosocopic control, a transcatheter aortic valve was implanted following s valvuloplasty. Once concluded the procedure, angiographic and pressure control was realized in order to confirm the valve function. Between November 2014 and May 2015, 6 patients were treated (4 males and 2 females), with a mean age of 78.83±5.66 years-old. The preoperative transvalvular gradient was 90.16±28.53mmHg and posterior to valve implant was 3.33±2.92mmHg (P<.05). Two patients had concomitant coronary artery disease which had been treated previously. One patient presented with acute right coronary artery occlusion which was immediately treated. However due to previous renal failure, postoperative sepsis and respiratory failure, the patient died one month later. It was concluded that our preliminary results showed that in selected patients percutaneous aortic valve implantation is a safe procedure with clinical improvement for treated patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Analysis of the Role of Carriership of Polymorphic Genotypes of ESR1, eNOS, and APOE4 Genes in the Development of Arterial Hypertension in Men.

PubMed

Dolgikh, O V; Zaitseva, N V; Nosov, A E; Krivtsov, A V; Dianova, D G; Kazakova, O A; Otavina, E A; Alikina, I N

2018-04-01

We studied the role of the carrier status for polymorphic loci of genes encoding estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein (ApoE) in the development of arterial hypertension in men. Conventionally healthy volunteers and 149 men with clinical manifestations of stage I-II arterial hypertension were examined. In men with arterial hypertension, the frequency of minor allele A of ESR1 gene was higher (27.5 vs. 9.5% in the reference group; χ 2 =4.43, p=0.04). The level of NO in the peripheral blood was also higher in the main group (χ 2 =3.93, p=0.047). The increase in NO concentration did not depend on the presence of polymorphic genotypes (GG and GT) of eNOS gene, but the decrease in ApoE level in blood serum was associated with TC genotype of APOE4 gene (p=0.04). Our results suggest that minor allele A of ESR1 gene is associated with the development of arterial hypertension in men. Reduced content of ApoE in blood serum of men with arterial hypertension was associated with APOE4 gene polymorphism. However, increased level of NO did not depend on polymorphic genotypes GG and GT of eNOS gene. These polymorphisms are of specific interest as additional markers of genetic predisposition to the development of arterial hypertension in middle-age men.

Microarray analysis to identify the similarities and differences of pathogenesis between aortic occlusive disease and abdominal aortic aneurysm.

PubMed

Wang, Guofu; Bi, Lechang; Wang, Gaofeng; Huang, Feilai; Lu, Mingjing; Zhu, Kai

2018-06-01

Objectives Expression profile of GSE57691 was analyzed to identify the similarities and differences between aortic occlusive disease and abdominal aortic aneurysm. Methods The expression profile of GSE57691 was downloaded from Gene Expression Omnibus database, including 20 small abdominal aortic aneurysm samples, 29 large abdominal aortic aneurysm samples, 9 aortic occlusive disease samples, and 10 control samples. Using the limma package in R, the differentially expressed genes were screened. Followed by enrichment analysis was performed for the differentially expressed genes using database for annotation, visualization, and integrated discovery online tool. Based on string online tool and Cytoscape software, protein-protein interaction network and module analyses were carried out. Moreover, integrated TF platform database and Cytoscape software were used for constructing transcriptional regulatory networks. Results As a result, 1757, 354, and 396 differentially expressed genes separately were identified in aortic occlusive disease, large abdominal aortic aneurysm, and small abdominal aortic aneurysm samples. UBB was significantly enriched in proteolysis related pathways with a high degree in three groups. SPARCL1 was another gene shared by these groups and regulated by NFIA, which had a high degree in transcriptional regulatory network. ACTB, a significant upregulated gene in abdominal aortic aneurysm samples, could be regulated by CLIC4, which was significantly enriched in cell motions. ACLY and NFIB were separately identified in aortic occlusive disease and small abdominal aortic aneurysm samples, and separately enriched in lipid metabolism and negative regulation of cell proliferation. Conclusions The downregulated UBB, NFIA, and SPARCL1 might play key roles in both aortic occlusive disease and abdominal aortic aneurysm, while the upregulated ACTB might only involve in abdominal aortic aneurysm. ACLY and NFIB were specifically involved in aortic occlusive

[Status of aortic valve reconstruction and Ross operation in aortic valve diseases].

PubMed

Sievers, Hans H

2002-08-01

At first glance the aortic valve is a relative simple valve mechanism connecting the left ventricle and the ascending aorta. Detailed analysis of the different components of the aortic valve including the leaflets and sinuses revealed a complex motion of each part leading to a perfect durable valve mechanism at rest and during exercise. Theoretically, the reconstruction or imitation of these structures in patients with aortic valve disease should lead to optimal results. Prerequisite is the exact knowledge of the important functional characteristics of the aortic valve. The dynamic behavior of the aortic root closely harmonizing with the leaflets not only warrants stress minimizing and valve durability, but also optimizes coronary flow, left ventricular function and aortic impedance. The newly discovered contractile capacity of the leaflets and the root components are important for tuning the dynamics. Isolated reconstruction of the aortic valve such as decalcification, commissurotomy, plication of ring or leaflets of a tricuspid aortic valve and cusp extension are seldom indicated in contrast to the reconstruction of the bicuspid insufficient valve. Proper indication and skilled techniques lead to excellent hemodynamic and clinical intermediate-term result up to 7 years after reconstruction. Latest follow-up revealed a mean aortic insufficiency of 0.7, maximal pressure gradient of 11.4 +/- 8.5 mm Hg with zero hospital or late mortality, reoperation or thromboembolic events in 22 patients. The reconstructive techniques for aortic root aneurysm and/or type A dissection according to David or Yacoub have become routine procedures in the last 10 years. The hemodynamic and clinical results are excellent with low reoperation rate and very low risk of thromboembolism. Generally, a maximal diameter of the root of 5 cm is indicative for performing the operation. In patients with Marfan's syndrome the reconstruction should be advanced even with smaller diameters especially

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report.

PubMed

Kamran, Mudassar; Fowler, Kathryn J; Mellnick, Vincent M; Sicard, Gregorio A; Narra, Vamsi R

2016-06-01

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.

Current status of aortic aneurysm surgery in Hong Kong.

PubMed

Cheng, S W

2001-11-01

To determine the epidemiology and the status of open and endovascular aortic surgery for aortic aneurysm in Hong Kong. Three separate data sources were obtained: (1) the Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the working group of vascular surgery; and (3) the department of surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution as well as audit of operative mortality was determined. Aortic aneurysm ranked tenth as the leading causes of death in Hong Kong, and the incidence is increasing. Almost 800 new cases were diagnosed each year, with 10% presenting as rupture, but the death rate for ruptured aneurysms was 80%. About half of all operations on aortic aneurysms was performed for rupture, and a significant number of newly diagnosed patients were not receiving surgery. In experienced centers, the operative mortality for elective and ruptured aneurysm have improved to 2% and 38% in recent years. A growing interest and number of endovascular repair operations were performed which has led to some concerns on patient selection and follow up. Similar to a worldwide trend, aortic aneurysm in Hong Kong is diagnosed more frequently. With the relatively high mortality for ruptured aneurysms, effective diagnosis and elective surgery on patients with aortic aneurysms in experienced vascular centers remained the best treatment. Since a majority of aneurysms remained untreated, patient and physician education is of paramount importance.

Natural history and outcome of aortic stenosis diagnosed prenatally.

PubMed Central

Simpson, J. M.; Sharland, G. K.

1997-01-01

OBJECTIVE: To document the growth of the left heart structures and outcome of fetuses with aortic stenosis. DESIGN: Retrospective echocardiographic and clinical study. SETTING: Tertiary centre for fetal cardiology. PATIENTS: 27 consecutive fetuses with aortic stenosis. MAIN OUTCOME MEASURES: Survival of affected fetuses. Measurement of left ventricular end diastolic volume (LVEDV), aortic root diameter, and ejection fraction. RESULTS: Before 25 weeks' gestation, the LVEDV was normal or increased in all cases. In six of eight fetuses studied sequentially, the LVEDV fell across normal centiles. Initial ejection fraction was reduced in 23 fetuses (88%). Before 28 weeks' gestation, the aortic root was normal in all but one case, but after 29 weeks, 11 of 13 fetuses had values below the 50th centile. In two fetuses prenatal aortic valvoplasty was attempted, 10 babies had postnatal interventions, and there were six survivors. Biventricular repair was attempted in eight cases, of whom five survived. A first stage Norwood operation was performed in three babies, of whom one survived. The four fetuses with the highest aortic root z scores had successful biventricular repair. The two fetuses with initially normal ejection fractions survived. Successful biventricular repair was achieved even where the LVEDV was below the 5th centile. CONCLUSIONS: In aortic stenosis diagnosed prenatally, failure of growth of the left ventricle and aortic root often occurs. The outcome of affected fetuses is better than previously reported. Prenatal echocardiography may assist selection of suitable candidates for biventricular versus Norwood repair. Images PMID:9093035

Aortic dimensions in Turner syndrome.

PubMed

Quezada, Emilio; Lapidus, Jodi; Shaughnessy, Robin; Chen, Zunqiu; Silberbach, Michael

2015-11-01

In Turner syndrome, linear growth is less than the general population. Consequently, to assess stature in Turner syndrome, condition-specific comparators have been employed. Similar reference curves for cardiac structures in Turner syndrome are currently unavailable. Accurate assessment of the aorta is particularly critical in Turner syndrome because aortic dissection and rupture occur more frequently than in the general population. Furthermore, comparisons to references calculated from the taller general population with the shorter Turner syndrome population can lead to over-estimation of aortic size causing stigmatization, medicalization, and potentially over-treatment. We used echocardiography to measure aortic diameters at eight levels of the thoracic aorta in 481 healthy girls and women with Turner syndrome who ranged in age from two to seventy years. Univariate and multivariate linear regression analyses were performed to assess the influence of karyotype, age, body mass index, bicuspid aortic valve, blood pressure, history of renal disease, thyroid disease, or growth hormone therapy. Because only bicuspid aortic valve was found to independently affect aortic size, subjects with bicuspid aortic valve were excluded from the analysis. Regression equations for aortic diameters were calculated and Z-scores corresponding to 1, 2, and 3 standard deviations from the mean were plotted against body surface area. The information presented here will allow clinicians and other caregivers to calculate aortic Z-scores using a Turner-based reference population. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Hybrid endovascular repair in aortic arch pathologies: a retrospective study.

PubMed

Ma, Xiaohui; Guo, Wei; Liu, Xiaoping; Yin, Tai; Jia, Xin; Xiong, Jiang; Zhang, Hongpeng; Wang, Lijun

2010-11-18

The aortic arch presents specific challenges to endovascular repair. Hybrid repair is increasingly evolving as an alternative option for selected patients, and promising initial results have been reported. The aim of this study was to introduce our experiences and evaluate mid-term results of supra aortic transpositions for extended endovascular repair of aortic arch pathologies. From December 2002 to January 2008, 25 patients with thoracic aortic aneurysms and dissections involving the aortic arch were treated with hybrid endovascular treatment in our center. Of the 25 cases, 14 were atherosclerotic thoracic aortic aneurysms and 11 were thoracic aortic dissection. The hybrid repair method included total-arch transpositions (15 cases) or hemi-arch transpositions (10 cases), and endovascular procedures. All hybrid endovascular procedures were completed successfully. Three early residual type-I endoleaks and one type-II endoleak were observed. Stroke occurred in three patients (8%) during the in-hospital stage. The perioperative mortality rate was 4%; one patients died post-operatively from catheter related complications. The average follow-up period was 15 ± 5.8 months (range, 1-41 months). The overall crude survival rate at 15 months was 92% (23/25). During follow-up, new late endoleaks and stent-raft related complications were not observed. One case (4%) developed a unilateral lower limb deficit at 17 days and was readmitted to hospital. In conclusion, the results are encouraging for endovascular aortic arch repair in combination with supra-aortic transposition in high risk cases. Aortic endografting offers good mid-term results. Mid-term results of the hybrid approach in elderly patients with aortic arch pathologies are satisfying.

G Protein–Coupled Receptor Kinase 2, With β-Arrestin 2, Impairs Insulin-Induced Akt/Endothelial Nitric Oxide Synthase Signaling in ob/ob Mouse Aorta

PubMed Central

Taguchi, Kumiko; Matsumoto, Takayuki; Kamata, Katsuo; Kobayashi, Tsuneo

2012-01-01

In type 2 diabetes, impaired insulin-induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response. Previously, we reported that this response was negatively regulated by G protein–coupled receptor kinase 2 (GRK2). In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. Endothelium-dependent relaxation was measured in aortic strips. GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. In ob/ob (vs. control [Lean]) aortas: 1) insulin-induced relaxation was reduced, and this deficit was prevented by GRK2 inhibitor, anti-GRK2 antibody, and an siRNA specifically targeting GRK2. The Lean aorta relaxation response was reduced to the ob/ob level by pretreatment with an siRNA targeting β-arrestin 2. 2) Insulin-stimulated Akt and eNOS phosphorylations were decreased. 3) GRK2 expression in membranes was elevated, and, upon insulin stimulation, this expression was further increased, but β-arrestin 2 was decreased. In ob/ob aortic membranes under insulin stimulation, the phosphorylations of Akt and eNOS were augmented by GRK2 inhibitor. In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction. PMID:22688330

G protein-coupled receptor kinase 2, with β-arrestin 2, impairs insulin-induced Akt/endothelial nitric oxide synthase signaling in ob/ob mouse aorta.

PubMed

Taguchi, Kumiko; Matsumoto, Takayuki; Kamata, Katsuo; Kobayashi, Tsuneo

2012-08-01

In type 2 diabetes, impaired insulin-induced Akt/endothelial nitric oxide synthase (eNOS) signaling may decrease the vascular relaxation response. Previously, we reported that this response was negatively regulated by G protein-coupled receptor kinase 2 (GRK2). In this study, we investigated whether/how in aortas from ob/ob mice (a model of type 2 diabetes) GRK2 and β-arrestin 2 might regulate insulin-induced signaling. Endothelium-dependent relaxation was measured in aortic strips. GRK2, β-arrestin 2, and Akt/eNOS signaling pathway proteins and activities were mainly assayed by Western blotting. In ob/ob (vs. control [Lean]) aortas: 1) insulin-induced relaxation was reduced, and this deficit was prevented by GRK2 inhibitor, anti-GRK2 antibody, and an siRNA specifically targeting GRK2. The Lean aorta relaxation response was reduced to the ob/ob level by pretreatment with an siRNA targeting β-arrestin 2. 2) Insulin-stimulated Akt and eNOS phosphorylations were decreased. 3) GRK2 expression in membranes was elevated, and, upon insulin stimulation, this expression was further increased, but β-arrestin 2 was decreased. In ob/ob aortic membranes under insulin stimulation, the phosphorylations of Akt and eNOS were augmented by GRK2 inhibitor. In mouse aorta, GRK2 may be, upon translocation, a key negative regulator of insulin responsiveness and an important regulator of the β-arrestin 2/Akt/eNOS signaling, which is implicated in diabetic endothelial dysfunction.

Study of the Pressure and Velocity Across the Aortic Valve

NASA Astrophysics Data System (ADS)

Kyung, Seo Young; Chung, Erica Soyun; Lee, Joo Hee; Kyung, Hayoung; Choi, Si Young

Biomechanics of the heart, requiring an extensive understanding of the complexity of the heart, have become the interests of many biomedical engineers in cardiology today. In order to study aortic valve disease, engineers have focused on the data obtained through bio-fluid flow analysis. To further this study, physical and computational analysis on the biomechanical determinants of blood flow in the stenosed aortic valve have been examined. These observations, along with the principles of cardiovascular physiology, confirm that when blood flows through the valve opening, pressure gradient across the valve is produced as a result of stenosis of the aortic valve. The aortic valve gradient is used to interpret the increase and decrease on each side of the defective valve. To compute different pressure gradients across the aortic valve, this paper analyzes Aortic Valve Areas (AVA) using simulations based on the continuity equation and Gorlin equation. The data obtained from such analysis consist of patients in the AS category that display mild Aortic Valve Velocity (AVV) and pressure gradient. Such correlation results in the construction of a dependent relationship between severe AS causing LV systolic dysfunction and the transaortic velocity.

Valve-sparing aortic root replacement in patients with Marfan syndrome enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions.

PubMed

Song, Howard K; Preiss, Liliana R; Maslen, Cheryl L; Kroner, Barbara; Devereux, Richard B; Roman, Mary J; Holmes, Kathryn W; Tolunay, H Eser; Desvigne-Nickens, Patrice; Asch, Federico M; Milewski, Rita K; Bavaria, Joseph; LeMaire, Scott A

2014-05-01

The long-term outcomes of aortic valve-sparing (AVS) root replacement in Marfan syndrome (MFS) patients remain uncertain. The study aim was to determine the utilization and outcomes of AVS root replacement in MFS patients enrolled in the Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). At the time of this analysis, 788 patients with MFS were enrolled in the GenTAC Registry, of whom 288 had undergone aortic root replacement. Patients who had undergone AVS procedures were compared to those who had undergone aortic valve replacement (AVR). AVS root replacement was performed in 43.5% of MFS patients, and the frequency of AVS was increased over the past five years. AVS patients were younger at the time of surgery (31.0 versus 36.3 years, p = 0.006) and more likely to have had elective rather than emergency surgery compared to AVR patients, in whom aortic valve dysfunction and aortic dissection was the more likely primary indication for surgery. After a mean follow up of 6.2 +/- 3.6 years, none of the 87 AVS patients had required reoperation; in contrast, after a mean follow up of 10.5 +/- 7.6 years, 11.5% of AVR patients required aortic root reoperation. Aortic valve function has been durable, with 95.8% of AVS patients having aortic insufficiency that was graded as mild or less. AVS root replacement is performed commonly among the MFS population, and the durability of the aortic repair and aortic valve function have been excellent to date. These results justify a continued use of the procedure in an elective setting. The GenTAC Registry will be a useful resource to assess the long-term durability of AVS root replacement in the future.

Association Between Gout and Aortic Stenosis

PubMed Central

Chang, Kevin; Yokose, Chio; Tenner, Craig; Oh, Cheongeun; Donnino, Robert; Choy-Shan, Alana; Pike, Virginia C.; Shah, Binita D.; Lorin, Jeffrey D.; Krasnokutsky, Svetlana; Sedlis, Steven P.; Pillinger, Michael H.

2017-01-01

Background An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. Methods We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. Results Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and non-aortic stenosis controls (n=224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n=24) of aortic stenosis subjects compared with 12.5% (n=28) of controls (unadjusted OR 1.90, 95% CI 1.05–3.48, p=0.038). Multivariate analysis retained significance only for gout (adjusted OR 2.08, 95% CI 1.00–4.32, p=0.049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs. 75.8 ± 1.0 years old, p=0.16). Conclusions Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications. PMID:27720853

Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells

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

Sun Yang; Sumi, Daigo; Kumagai, Yoshito

2006-07-01

Although 2,4,6-trinitrotoluene (TNT) has been found to uncouple nitric oxide synthase (NOS), thereby leading to reactive oxygen species (ROS), cellular response against TNT still remains unclear. Exposure of bovine aortic endothelial cells (BAECs) to TNT (100 {mu}M) resulted in serine 1179 phosphorylation of endothelial NOS (eNOS). With specific inhibitors (wortmannin and LY294002), we found that PI3K/Akt signaling participated in the eNOS phosphorylation caused by TNT, whereas the ERK pathway did not. ROS were generated following exposure of BAECs to TNT. However, TNT-mediated phosphorylation of either eNOS or Akt was drastically blocked by NAC and PEG-CAT. Interestingly, pretreatment with apocynin, amore » specific inhibitor for NADPH oxidase, diminished the phosphorylation of eNOS and Akt. These results suggest that TNT affects NADPH oxidase, thereby generating hydrogen peroxide, which is capable of activating PI3K/Akt signaling associated with eNOS Ser 1179 phosphorylation.« less

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.

PubMed

2017-08-29

Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1-22.2; P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P <0.0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair

PubMed Central

2017-01-01

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. Methods In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Results Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1–22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the

Current indications for stentless aortic bioprostheses.

PubMed

Hegazy, Yasser Y; Rayan, Amr; Bauer, Stefan; Keshk, Noha; Bauer, Kerstin; Ennker, Ina; Ennker, Jürgen

2018-01-01

The best aortic prostheses have been debated for decades. The introduction of stentless aortic bioprostheses was aimed at improving hemodynamics and potentially the durability of aortic bioprostheses. Despite the good short- and long-term outcomes after implantation of stentless aortic bioprostheses, their use remains limited owing to the technically demanding implantation techniques. Nevertheless, stentless aortic bioprostheses might be of special benefit in certain indications, where they could be a valuable addition to the surgical armamentarium.

Role of eNOS in water exchange index maintenance-MRI studies

NASA Astrophysics Data System (ADS)

Atochin, D.; Litvak, M.; Huang, S.; Kim, Y. R.; Huang, P.

2017-08-01

Stroke studies employ experimental models of cerebral ischemic and reperfusion injury in rodents. MRI provides valuable supravital data of cerebral blood flow and brain tissue damage. This paper presents MRI applications for cerebral blood flow research in mice lines with impaired nitric oxide production by endothelial nitric oxide synthase. Our data demonstrates that specific modifications of MRI methodology in transgenic mouse models help to evaluate the role of eNOS in the brain-blood barrier function.

Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

PubMed

Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

2018-05-01

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm.

PubMed

Gibson, Christine; Nielsen, Cory; Alex, Ramona; Cooper, Kimbal; Farney, Michael; Gaufin, Douglas; Cui, Jason Z; van Breemen, Cornelis; Broderick, Tom L; Vallejo-Elias, Johana; Esfandiarei, Mitra

2017-07-01

Regular low-impact physical activity is generally allowed in patients with Marfan syndrome, a connective tissue disorder caused by heterozygous mutations in the fibrillin-1 gene. However, being above average in height encourages young adults with this syndrome to engage in high-intensity contact sports, which unfortunately increases the risk for aortic aneurysm and rupture, the leading cause of death in Marfan syndrome. In this study, we investigated the effects of voluntary (cage-wheel) or forced (treadmill) aerobic exercise at different intensities on aortic function and structure in a mouse model of Marfan syndrome. Four-week-old Marfan and wild-type mice were subjected to voluntary and forced exercise regimens or sedentary lifestyle for 5 mo. Thoracic aortic tissue was isolated and subjected to structural and functional studies. Our data showed that exercise improved aortic wall structure and function in Marfan mice and that the beneficial effect was biphasic, with an optimum at low intensity exercise (55-65% V̇o 2max ) and tapering off at a higher intensity of exercise (85% V̇o 2max ). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinases 2 and 9 within the aortic wall. These findings present the first evidence of potential beneficial effects of mild exercise on the structural integrity of the aortic wall in Marfan syndrome associated aneurysm. Our finding that moderate, but not strenuous, exercise protects aortic structure and function in a mouse model of Marfan syndrome could have important implications for the medical care of young Marfan patients. NEW & NOTEWORTHY The present study provides conclusive scientific evidence that daily exercise can improve aortic health in a mouse model of Marfan syndrome associated aortic aneurysm, and it establishes the threshold for the exercise intensity beyond which exercise may not be as protective. These findings establish a platform

Correlation of echo-Doppler aortic valve regurgitation index with angiographic aortic regurgitation severity.

PubMed

Chen, Ming; Luo, Huai; Miyamoto, Takashi; Atar, Shaul; Kobal, Sergio; Rahban, Masoud; Brasch, Andrea V; Makkar, Rajendra; Neuman, Yoram; Naqvi, Tasneem Z; Tolstrup, Kirsten; Siegel, Robert J

2003-09-01

We assessed aortic regurgitation (AR) severity by utilizing multiple echo-Doppler variables in comparison with AR severity by aortic root angiography. Patients were divided into 3 groups: mild, moderate, and severe. An AR index (ARI) was developed, comprising 5 echocardiographic parameters: ratio of color AR jet height to left ventricular outlet flow diameter, AR signal density from continuous-wave Doppler, pressure half-time, left ventricular end-diastolic diameter, and aortic root diameter. There was a strong correlation between AR severity by angiography and the calculated echo-Doppler ARI (r = 0.84, p = 0.0001). As validated by aortic angiography, the ARI is an accurate reflection of AR severity.

Comparison of aortic media changes in patients with bicuspid aortic valve stenosis versus bicuspid valve insufficiency and proximal aortic aneurysm.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Borger, Michael A; Kuntze, Thomas

2013-12-01

The aim of this study was to evaluate aortic media changes in bicuspid aortic valve (BAV) patients who underwent aortic valve replacement (AVR) and simultaneous replacement of the proximal aorta for BAV stenosis vs BAV insufficiency. Review of our institutional BAV database identified a subgroup of 79 consecutive BAV patients (mean age 52.3 ± 13 years, 81% men) with BAV stenosis or insufficiency and concomitant proximal aortic dilatation of ≥50 mm who underwent AVR and simultaneous replacement of proximal aorta from 1995 through 2005. All cases of BAV disease and concomitant ascending aortic dilatation of 40-50 mm underwent isolated AVR and therefore were excluded from this analysis. Proximal aortic media elastic fibre loss (EFL) was assessed (graded 0 to 3+) and compared between patients with BAV stenosis (Group I, n = 44) vs BAV insufficiency (Group II, n = 35). Follow-up (690 patient-years) was 100% complete and 9.1 ± 4.6 years long. Mean aortic media EFL was 1.3 ± 0.7 in Group I vs 2.5 ± 0.8 in Group II (P = 0.03). Moderate/severe EFL (i.e. defined as grade 2+/3+) was found in 13 patients (29%) in Group I vs 28 patients (80%) in Group II (P < 0.001). Logistic regression identified BAV insufficiency as the strongest predictor of moderate/severe EFL (OR 9.3; 95% CI 3.2-29.8, P < 0.001). Valve-related event-free survival was 64 ± 8% in Group I vs 93% ± 5% in Group II at 10 years postoperatively (P = 0.05). A total of 4 patients (5%, 3 from Group I and 1 from Group II) underwent redo aortic root surgery for prosthetic valve endocarditis during follow-up. Patients with BAV insufficiency and a proximal aorta of ≥50 mm have a significantly higher rate of moderate/severe EFL as compared to their counterparts with BAV stenosis.

Testosterone Deficiency Accelerates Neuronal and Vascular Aging of SAMP8 Mice: Protective Role of eNOS and SIRT1

PubMed Central

Ota, Hidetaka; Akishita, Masahiro; Akiyoshi, Takuyu; Kahyo, Tomoaki; Setou, Mitsutoshi; Ogawa, Sumito; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi

2012-01-01

Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD+-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging. PMID:22238626

Central Role of eNOS in the Maintenance of Endothelial Homeostasis

PubMed Central

Rodriguez-Mateos, Ana; Kelm, Malte

2015-01-01

Abstract Significance: Disruption of endothelial function is considered a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase (eNOS) is a central regulator of cellular function that is important to maintain endothelial homeostasis. Recent Advances: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue's demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells (ECs) and attraction of circulating angiogenic cells (CAC), both of which support repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of NO-dependent vasodilation, whereas EMP are upcoming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with NO representing a central signaling molecule. Critical Issues: Improvements of reproducibility and observer independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research. Future Directions: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance. Antioxid. Redox Signal. 22, 1230–1242. PMID:25330054

Myeloid mineralocorticoid receptor deficiency inhibits aortic constriction-induced cardiac hypertrophy in mice.

PubMed

Li, Chao; Zhang, Yu Yao; Frieler, Ryan A; Zheng, Xiao Jun; Zhang, Wu Chang; Sun, Xue Nan; Yang, Qing Zhen; Ma, Shu Min; Huang, Baozhuan; Berger, Stefan; Wang, Wang; Wu, Yong; Yu, Ying; Duan, Sheng Zhong; Mortensen, Richard M

2014-01-01

Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation.

Correlation between systolic transvalvular flow and proximal aortic wall changes in bicuspid aortic valve stenosis.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Scholle, Thorsten; Fey, Beatrix; Theis, Bernhard; Petersen, Iver; Borger, Michael A; Kuntze, Thomas

2014-08-01

The purpose of this study was to analyse the correlation between preoperative systolic transvalvular flow patterns and proximal aortic wall lesions in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. A total of 48 consecutive patients with BAV stenosis (mean age 58 ± 9 years, 65% male) underwent aortic valve replacement (AVR) ± proximal aortic surgery from January 2012 through February 2013. Preoperative cardiac phase-contrast cine magnetic resonance imaging (MRI) assessment was performed in all patients in order to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, two aortic wall samples (i.e. area of the maximal stress (jet sample) and the opposite aortic wall (control sample)) were collected during AVR surgery. Aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3). Histological sum score (0-21) was separately calculated and compared between the two aortic samples (i.e. jet sample vs control sample). An eccentric transvalvular flow jet hitting the proximal aortic wall could be identified in all 48 (100%) patients. The mean histological sum score was significantly higher in the jet sample vs control sample areas of the aorta (i.e. 4.1 ± 1.8 vs 2.2 ± 1.5, respectively) (P = 0.02). None of the patients had a higher sum score value in the control sample. Our study demonstrates a strong correlation between the systolic pattern of the transvalvular flow jet and asymmetric proximal aortic wall changes in patients undergoing AVR for BAV stenosis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans.

PubMed

Casey, Darren P; Ueda, Kenichi; Wegman-Points, Lauren; Pierce, Gary L

2017-10-01

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser 1177 , the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser 1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser 1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser 1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser 1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in

Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS.

PubMed

Sharma, Ashok Kumar; Bharti, Saurabh; Bhatia, Jagriti; Nepal, Saroj; Malik, Salma; Ray, Ruma; Kumari, Santosh; Arya, Dharamvir Singh

2012-11-01

Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-α, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS. Copyright © 2012 Elsevier Inc. All rights reserved.

Blunt traumatic aortic injuries of the ascending aorta and aortic arch: a clinical multicentre study.

PubMed

Mosquera, Victor X; Marini, Milagros; Muñiz, Javier; Gulias, Daniel; Asorey-Veiga, Vanesa; Adrio-Nazar, Belen; Herrera, José M; Pradas-Montilla, Gonzalo; Cuenca, José J

2013-09-01

To report the clinical and radiological characteristics, management and outcomes of traumatic ascending aorta and aortic arch injuries. Historic cohort multicentre study including 17 major trauma patients with traumatic aortic injury from January 2000 to January 2011. The most common mechanism of blunt trauma was motor-vehicle crash (47%) followed by motorcycle crash (41%). Patients sustaining traumatic ascending aorta or aortic arch injuries presented a high proportion of myocardial contusion (41%); moderate or greater aortic valve regurgitation (12%); haemopericardium (35%); severe head injuries (65%) and spinal cord injury (23%). The 58.8% of the patients presented a high degree aortic injury (types III and IV). Expected in-hospital mortality was over 50% as defined by mean TRISS 59.7 (SD 38.6) and mean ISS 48.2 (SD 21.6) on admission. Observed in-hospital mortality was 53%. The cause of death was directly related to the ATAI in 45% of cases, head and abdominal injuries being the cause of death in the remaining 55% cases. Long-term survival was 46% at 1 year, 39% at 5 years, and 19% at 10 years. Traumatic aortic injuries of the ascending aorta/arch should be considered in any major thoracic trauma patient presenting cardiac tamponade, aortic valve regurgitation and/or myocardial contusion. These aortic injuries are also associated with a high incidence of neurological injuries, which can be just as lethal as the aortic injury, so treatment priorities should be modulated on an individual basis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Surgical treatment of pararenal aortic aneurysms in the elderly.

PubMed

Illuminati, G; D'Urso, A; Ceccanei, G; Caliò, F; Vietri, F

2007-12-01

Until fenestrated endografts will become the standard treatment of pararenal aortic aneurysms, open surgical repair will currently be employed for the repair of this condition. Suprarenal aortic control and larger surgical dissection represent additional technical requirements for the treatment of pararenal aneurysms compared to those of open infrarenal aortic aneurysms, which may be followed by an increased operative mortality and morbidity rate. As this may be especially true when dealing with pararenal aneurysms in an elderly patients' population, we decided to retrospectively review our results of open pararenal aortic aneurysm repair in elderly patients, in order to compare them with those reported in the literature. Twenty-one patients over 75 years of age were operated on for pararenal aortic aneurysms in a ten-year period. Exposure of the aorta was obtained by means of a retroperitoneal access, through a left flank incision on the eleventh rib. When dealing with interrenal aortic aneurysm the left renal artery was revascularized with a retrograde bypass arising from the aortic graft, proximally bevelled on the ostium of the right renal artery. Two patients died of acute intestinal ischemia, yielding a postoperative mortality of 9.5%. Nonfatal complications included 2 pleural effusions, a transitory rise in postoperative serum creatinine levels in 3 cases, and one retroperitoneal hematoma. Mean renal ischemia time was 23 min, whereas mean visceral ischemia time was 19 min. Mean inhospital stay was 11 days. Pararenal aortic aneurysms in the elderly can be surgically repaired with results that are similar to those obtained in younger patients.

The incidence and effect of noncylindrical neck morphology on outcomes after endovascular aortic aneurysm repair in the Global Registry for Endovascular Aortic Treatment.

PubMed

Shutze, William; Suominem, Velipekka; Jordan, William; Cao, Piergiorgio; Oweida, Steven; Milner, Ross

2018-05-23

�months and 17.8 ± 15.8 months for the cylindrical and noncylindrical cohorts, respectively (P < .001). The Cox multivariate regression models demonstrated female gender and maximum AAA diameter were significant risk factors for subsequent reintervention (overall, device-related, and endoleak-specific). Women were 2.2 times as likely to require device-related intervention during the follow-up period compared with men (P < .001). Neck shape morphology was not a significant predictor, except for device-related intervention, for which cylindrical necks (binary definition) resulted in a slightly elevated risk (1.5 times; P = .03). Noncylindrical neck morphology was more common in women and was associated with an increased use of aortic extender cuffs but did not increase the risk of intervention. Female gender and AAA diameter were associated with an increased need for reintervention. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Association Between Gout and Aortic Stenosis.

PubMed

Chang, Kevin; Yokose, Chio; Tenner, Craig; Oh, Cheongeun; Donnino, Robert; Choy-Shan, Alana; Pike, Virginia C; Shah, Binita D; Lorin, Jeffrey D; Krasnokutsky, Svetlana; Sedlis, Steven P; Pillinger, Michael H

2017-02-01

An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and nonaortic stenosis controls (n = 224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n = 24) of aortic stenosis subjects compared with 12.5% (n = 28) of controls (unadjusted odds ratio 1.90, 95% confidence interval 1.05-3.48, P = .038). Multivariate analysis retained significance only for gout (adjusted odds ratio 2.08, 95% confidence interval 1.00-4.32, P = .049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 ± 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 ± 1.8 vs 75.8 ± 1.0 years old, P = .16). Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for, the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications. Published by Elsevier Inc.

Increased levels of interleukin-22 in thoracic aorta and plasma from patients with acute thoracic aortic dissection.

PubMed

Ye, Jing; Wang, Menglong; Jiang, Huimin; Ji, Qingwei; Huang, Ying; Liu, Jianfang; Zeng, Tao; Xu, Yao; Wang, Zhen; Lin, Yingzhong; Wan, Jun

2017-11-03

Interleukin (IL)-22 plays important roles in the development of arterial disease, including atherosclerosis and hypertension. However, the relationship between IL-22 and acute thoracic aortic dissection (TAD) remains unknown. Blood samples were collected from patients with chest pain who underwent computed tomography angiography of the thoracic aorta but had no known preoperative diagnosis of coronary artery disease, peripheral artery disease, arthritis, and/or membranous nephropathy. Patients were divided into non-AD (NAD) and TAD groups, and the plasma concentrations of IL-22, IL-6 and tumor necrosis factor (TNF)-α were measured. In addition, aortic tissue samples from acute TAD patients and normal donors were collected, and the expression levels of IL-22 and IL-22 receptor 1 (IL-22R1) were measured. IL-22, IL-6 and TNF-α levels were significantly higher in acute TAD patients than in NAD patients (IL-22, NAD group: 27.0 (19.1, 38.6) pg/ml vs. TAD group: 32.9 (20.6, 58.3) pg/ml, p<0.0001). The correlation analysis showed that IL-22 levels were positively correlated with levels of IL-6, TNF-α, fasting glucose, blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that IL-22 was independently associated with the presence of acute TAD (OR 1.169, 95% CI 1.069 to 1.277; p=0.001). In addition, compared with aortic tissue of normal controls, TAD aortas showed increased expression of IL-22 and IL-22R1, especially in the torn section (IL-22, non-torn section: 2.8±0.5/HPF vs. torn section 2.8±0.5/HPF, p<0.001). Additionally, macrophage but not T lymphocyte infiltration was significantly increased in the torn section (Macrophage, non-torn section: 2.2±0.6/HPF vs. torn section 5.7±1.2/HPF, p<0.001; T lymphocyte, non-torn section: 2.7±0.9/HPF vs. torn section 2.4±0.5/HPF, p=0.28), as evidenced by increased positive staining for the macrophage marker CD68, as opposed to the T cell marker CD3. IL-22 levels may

Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions.

PubMed

Khanafer, Khalil M; Bull, Joseph L; Upchurch, Gilbert R; Berguer, Ramon

2007-01-01

The numerical models of abdominal aortic aneurysm (AAA) in use do not take into account the non-Newtonian behavior of blood and the development of local turbulence. This study examines the influence of pulsatile, turbulent, non-Newtonian flow on fluid shear stresses and pressure changes under rest and exercise conditions. We numerically analyzed pulsatile turbulent flow, using simulated physiological rest and exercise waveforms, in axisymmetric-rigid aortic aneurysm models (AAMs). Discretization of governing equations was achieved using a finite element scheme. Maximum turbulence-induced shear stress was found at the distal end of an AAM. In large AAMs (dilated to undilated diameter ratio = 3.33) at peak systolic flow velocity, fluid shear stress during exercise is 70.4% higher than at rest. Our study provides a numerical, noninvasive method for obtaining detailed data on the forces generated by pulsatile turbulent flow in AAAs that are difficult to study in humans and in physical models. Our data suggest that increased flow turbulence results in increased shear stress in aneurysms. While pressure readings are fairly uniform along the length of an aneurysm, the kinetic energy generated by turbulence impacting on the wall of the distal half of the aneurysm increases fluid and wall shear stress at this site. If the increased fluid shear stress results in further dilation and hence further turbulence, wall stress may be a mechanism for aneurysmal growth and eventual rupture.

Update on the prevention of death from ruptured abdominal aortic aneurysm.

PubMed

Jacomelli, Jo; Summers, Lisa; Stevenson, Anne; Lees, Tim; Earnshaw, Jonothan J

2017-09-01

Objectives To monitor the early effect of a national population screening programme for abdominal aortic aneurysm in 65-year-old men. Setting The study used national statistics for death rates from abdominal aortic aneurysm (Office of National Statistics) and hospital admission data in England (Hospital Episode Statistics). Methods Information concerning deaths from abdominal aortic aneurysm (ruptured and non-ruptured) (1999-2014) and hospital admissions for ruptured abdominal aortic aneurysm (2000-2015) was examined. Results The absolute number of deaths from abdominal aortic aneurysm in men and women aged 65 and over has decreased by around 30% from 2001 to 2014, but as the population has increased, the relative reduction was 45.6% and 40.0%, respectively. Some 65% of all abdominal aortic aneurysm deaths are in men aged over 65; women aged 65 and over account for around 31%. Deaths from ruptured abdominal aortic aneurysm in men aged 60-74 (the screened group) appear to be declining at the same rate as in men aged 75 and over. The relative decline in admissions to hospital with ruptured abdominal aortic aneurysm may be greater in men and women aged 60-74 (which contains the screened group of men), than those older, giving the first possible evidence that abdominal aortic aneurysm screening is having an effect. Conclusion The death rate from abdominal aortic aneurysm is declining rapidly in England. There is the first evidence that screening may be contributing to this reduction.

Tribbles 3: A potential player in diabetic aortic remodelling.

PubMed

Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Ding, Wen-yuan; Zhang, Yun; Zhong, Ming; Zhang, Wei

2016-01-01

Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes. © The Author(s) 2015.

Comparison of valvular resistance, stroke work loss, and Gorlin valve area for quantification of aortic stenosis. An in vitro study in a pulsatile aortic flow model.

PubMed

Voelker, W; Reul, H; Nienhaus, G; Stelzer, T; Schmitz, B; Steegers, A; Karsch, K R

1995-02-15

Valvular resistance and stroke work loss have been proposed as alternative measures of stenotic valvular lesions that may be less flow dependent and, thus, superior over valve area calculations for the quantification of aortic stenosis. The present in vitro study was designed to compare the impacts of valvular resistance, stroke work loss, and Gorlin valve area as hemodynamic indexes of aortic stenosis. In a pulsatile aortic flow model, rigid stenotic orifices in varying sizes (0.5, 1.0, 1.5 and 2.0 cm2) and geometry were studied under different hemodynamic conditions. Ventricular and aortic pressures were measured to determine the mean systolic ventricular pressure (LVSPm) and the transstenotic pressure gradient (delta Pm). Transvalvular flow (Fm) was assessed with an electromagnetic flowmeter. Valvular resistance [VR = 1333.(delta Pm/Fm)] and stroke work loss [SWL = 100.(delta Pm/LVSPm)] were calculated and compared with aortic valve area [AVA = Fm/(50 square root of delta Pm)]. The measurements were performed for a large range of transvalvular flows. At low-flow states, flow augmentation (100-->200 mL/s) increased calculated valvular resistance between 21% (2.0 cm2 orifice) and 66% (0.5-cm2 orifice). Stroke work loss demonstrated an increase from 43% (2.0 cm2) to 100% (1.0 cm2). In contrast, Gorlin valve area revealed only a moderate change from 29% (2.0 cm2) to 5% (0.5 cm2). At physiological flow rates, increase in transvalvular flow (200-->300 mL/s) did not alter calculated Gorlin valve area, whereas valvular resistance and stroke work loss demonstrated a continuing increase. Our experimental results were adopted to interpret the results of three clinical studies in aortic stenosis. The flow-dependent increase of Gorlin valve area, which was found in the cited clinical studies, can be elucidated as true further opening of the stenotic valve but not as a calculation error due to the Gorlin formula. Within the physiological range of flow, calculated aortic valve

Effect of personalized external aortic root support on aortic root motion and distension in Marfan syndrome patients.

PubMed

Izgi, Cemil; Nyktari, Evangelia; Alpendurada, Francisco; Bruengger, Annina Studer; Pepper, John; Treasure, Tom; Mohiaddin, Raad

2015-10-15

Personalized external aortic root support (PEARS) is a novel surgical approach with the aim of stabilizing the aortic root size and decreasing risk of dissection in Marfan syndrome patients. A bespoke polymer mesh tailored to each patient's individual aorta shape is produced by modeling and then surgically implanted. The aim of this study is to assess the mechanical effects of PEARS on the aortic root systolic downward motion (an important determinant of aortic wall stress), aortic root distension and on the left ventricle (LV). A cohort of 27 Marfan patients had a prophylactic PEARS surgery between 2004 and 2012 with 24 having preoperative and follow-up cardiovascular magnetic resonance imaging studies. Systolic downward aortic root motion, aortic root distension, LV volumes/mass and mitral annular systolic excursion before the operation and in the latest follow-up were measured randomly and blinded. After a median follow-up of 50.5 (IQR 25.5-72) months following implantation of PEARS, systolic downward motion of aortic root was significantly decreased (12.6±3.6mm pre-operation vs 7.9±2.9mm latest follow-up, p<0.00001). There was a tendency for a decrease in systolic aortic root distension but this was not significant (median 4.5% vs 2%, p=0.35). There was no significant change in LV volumes, ejection fraction, mass and mitral annular systolic excursion in follow-up. PEARS surgery decreases systolic downward aortic root motion which is an important determinant of longitudinal aortic wall stress. Aortic wall distension and Windkessel function are not significantly impaired in the follow-up after implantation of the mesh which is also supported by the lack of deterioration of LV volumes or mass. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Current role of endovascular therapy in Marfan patients with previous aortic surgery

PubMed Central

Akin, Ibrahim; Kische, Stephan; Rehders, Tim C; Chatterjee, Tushar; Schneider, Henrik; Körber, Thomas; Nienaber, Christoph A; Ince, Hüseyin

2008-01-01

The Marfan syndrome is a heritable disorder of the connective tissue which affects the cardiovascular, ocular, and skeletal system. The cardiovascular manifestation with aortic root dilatation, aortic valve regurgitation, and aortic dissection has a prevalence of 60% to 90% and determines the premature death of these patients. Thirty-four percent of the patients with Marfan syndrome will have serious cardiovascular complications requiring surgery in the first 10 years after diagnosis. Before aortic surgery became available, the majority of the patients died by the age of 32 years. Introduction in the aortic surgery techniques caused an increase of the 10 year survival rate up to 97%. The purpose of this article is to give an overview about the feasibility and outcome of stent-graft placement in the descending thoracic aorta in Marfan patients with previous aortic surgery. PMID:18629349

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

PubMed Central

Cury, Marcelo; Zeidan, Fernanda; Lobato, Armando C.

2013-01-01

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research. PMID:23401778

Bovine aortic arch with supravalvular aortic stenosis.

PubMed

Idhrees, Mohammed; Cherian, Vijay Thomas; Menon, Sabarinath; Mathew, Thomas; Dharan, Baiju S; Jayakumar, K

2016-09-01

A 5-year-old boy was diagnosed to have supravalvular aortic stenosis (SVAS). On evaluation of CT angiogram, there was associated bovine aortic arch (BAA). Association of BAA with SVAS has not been previously reported in literature, and to best of our knowledge, this is the first case report of SVAS with BAA. Recent studies show BAA as a marker for aortopathy. SVAS is also an arteriopathy. In light of this, SVAS can also possibly be a manifestation of aortopathy associated with BAA. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Abdominal aortic aneurysm neck remodeling after Anaconda stent graft implantation.

PubMed

Vukovic, Elisabeth; Czerny, Martin; Beyersdorf, Friedhelm; Wolkewitz, Martin; Berezowski, Mikolaj; Siepe, Matthias; Blanke, Philipp; Rylski, Bartosz

2018-05-24

The aim of this study was to define how the proximal landing zone changes geometrically after endovascular abdominal aortic aneurysm repair (EVAR) with the Anaconda (Vascutek, Inchinnan, United Kingdom) stent graft. Among 230 patients who underwent Anaconda stent graft implantation between 2005 and 2014, we included 126 with adequate computed tomography (CT) image quality and follow-up. CT analysis entailed the geometric changes in the main body, proximal rings, and proximal landing zone. The median CT follow-up was 2.0 years (345.8 patients-years). The proximal portion of the main body ring system flattened within the first year after EVAR, resulting in an up to 30° increase in the upper ring's angle in 40% patients and up to 40° increase in 24% patients. One year after EVAR, the upper ring angle increase slowed down. Aortic diameter measured at the level of the upper and lower ring expanded by 2 to 4 mm within 1 year, but remained unchanged afterward. The main body migrated continuously down toward the aortic bifurcation, attaining an average 6-mm increase in the distance between the superior mesenteric artery and main body within 4 years. Freedom from endoleak type IA was 95 ± 2% and 93 ± 3% after 1 and 4 years, respectively. The Anaconda main body ring system in its proximal portion flattens within the first year after EVAR, leading to an increase of 2 to 4 mm in the proximal landing zone's aortic diameter. The main body migrates slowly but continuously down toward the aortic bifurcation. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

[Percutaneously implantable aortic valve: the JenaValve concept evolution].

PubMed

Figulla, Hans R; Ferrari, Markus

2006-10-01

Due to the increasing incidence of severe aortic stenosis in old and multimorbid patients, the percutaneous implantation of aortic valve-carrying stents has become an alternative to the surgical replacement of aortic valves. Starting in 1995, the authors developed a self-expanding stent which transferred the necessary forces for anchoring up to the aorta ascendens-a conception taken over from CoreValve. The further improvement of this idea over the past 11 years has led to a self-expanding, relatively short stent-valve system that is reliably positioned in the cusps of the old aortic valve and holds the old valve like a paper clip, thus transferring the holding forces physiologically. As compared to conventional systems, the sophisticated insertion catheter requires further chronic animal tests so as to represent a true alternative to the conventional surgical procedure.

Outcome-based anatomic criteria for defining the hostile aortic neck.

PubMed

Jordan, William D; Ouriel, Kenneth; Mehta, Manish; Varnagy, David; Moore, William M; Arko, Frank R; Joye, James; de Vries, Jean-Paul P M

2015-06-01

There is abundant evidence linking hostile proximal aortic neck anatomy to poor outcome after endovascular aortic aneurysm repair (EVAR), yet the definition of hostile anatomy varies from study to study. This current analysis was undertaken to identify anatomic criteria that are most predictive of success or failure at the aortic neck after EVAR. The study group comprised 221 patients in the Aneurysm Treatment using the Heli-FX Aortic Securement System Global Registry (ANCHOR) clinical trial, a population enriched with patients with challenging aortic neck anatomy and failure of sealing. Imaging protocols were not protocol specified but were performed according to the institution's standard of care. Core laboratory analysis assessed the three-dimensional centerline-reformatted computed tomography scans. Failure at the aortic neck was defined by type Ia endoleak occurring at the time of the initial endograft implantation or during follow-up. Receiver operating characteristic curve analysis was used to assess the value of each anatomic measure in the classification of aortic neck success and failure and to identify optimal thresholds of discrimination. Binary logistic regression was performed after excluding highly intercorrelated variables, creating a final model with significant predictors of outcome after EVAR. Among the 221 patients, 121 (54.8%) remained free of type Ia endoleak and 100 (45.2%) did not. Type Ia endoleaks presented immediately after endograft deployment in 58 (58.0%) or during follow-up in 42 (42.0%). Receiver operating characteristic curve analysis identified 12 variables where the classification of patients with type Ia endoleak was significantly more accurate than chance alone. Increased aortic neck diameter at the lowest renal artery (P = .013) and at 5 mm (P = .008), 10 mm (P = .008), and 15 mm (P = .010) distally; aneurysm sac diameter (P = .001), common iliac artery diameters (right, P = .012; left, P = .032), and a conical (P = .049) neck

Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells.

PubMed

Sugiyama, Toru; Levy, Bruce D; Michel, Thomas

2009-05-08

Tetrahydrobiopterin (BH4) is a key redox-active cofactor in endothelial isoform of NO synthase (eNOS) catalysis and is an important determinant of NO-dependent signaling pathways. BH4 oxidation is observed in vascular cells in the setting of the oxidative stress associated with diabetes. However, the relative roles of de novo BH4 synthesis and BH4 redox recycling in the regulation of eNOS bioactivity remain incompletely defined. We used small interference RNA (siRNA)-mediated "knockdown" GTP cyclohydrolase-1 (GTPCH1), the rate-limiting enzyme in BH4 biosynthesis, and dihydrofolate reductase (DHFR), an enzyme-recycling oxidized BH4 (7,8-dihydrobiopterin (BH2)), and studied the effects on eNOS regulation and biopterin metabolism in cultured aortic endothelial cells. Knockdown of either DHFR or GTPCH1 attenuated vascular endothelial growth factor (VEGF)-induced eNOS activity and NO production; these effects were recovered by supplementation with BH4. In contrast, supplementation with BH2 abolished VEGF-induced NO production. DHFR but not GTPCH1 knockdown increased reactive oxygen species (ROS) production. The increase in ROS production seen with siRNA-mediated DHFR knockdown was abolished either by simultaneous siRNA-mediated knockdown of eNOS or by supplementing with BH4. In contrast, addition of BH2 increased ROS production; this effect of BH2 was blocked by BH4 supplementation. DHFR but not GTPCH1 knockdown inhibited VEGF-induced dephosphorylation of eNOS at the inhibitory site serine 116; these effects were recovered by supplementation with BH4. These studies demonstrate a striking contrast in the pattern of eNOS regulation seen by the selective modulation of BH4 salvage/reduction versus de novo BH4 synthetic pathways. Our findings suggest that the depletion of BH4 is not sufficient to perturb NO signaling, but rather that concentration of intracellular BH2, as well as the relative concentrations of BH4 and BH2, together play a determining role in the redox

Thoracic Endovascular Aortic Repair Combined with Assistant Techniques and Devices for the Treatment of Acute Complicated Stanford Type B Aortic Dissections Involving Aortic Arch.

PubMed

Zhang, Tianhua; Jiang, Weiliang; Lu, Haitao; Liu, Jianfeng

2016-04-01

The present study retrospectively reviewed and evaluated the effectiveness of thoracic endovascular aortic repair (TEVAR) combined with assistant techniques and devices for the treatment of acute complicated Stanford type B aortic dissections involving aortic arch. Fifty-six patients with acute complicated Stanford type B aortic dissection involving aortic arch were treated with TEVAR combined with hybrid procedure, chimney-graft technique, and branched stent grafts from January 2009 to March 2014. Seventeen patients undergone TEVAR combined with hybrid technique. Technical success was achieved in 94.1% with 5.8% of early mortality. Strokes occurred in a patient developing paraplegia, who completely recovered after lumbar drainage. Cardiocirculatory and pulmonary complications, bypass dysfunction or severe endoleak was not observed. Thirty patients undergone TEVAR combined with chimney technique with 100% technical success rate. Chimney-stent compression was observed in 1 patient, and another bare stent was deployed inside the first one. Three patients (10%) died during the study period. Immediate postoperative type I endoleak was detected in 4 cases (13.3%). TEVAR assisted by Castor branched aortic stent grafts in 9 patients was successful. Mortality during perioperative period and 30 days after TEVAR was null. No serious complications such as strokes, acute myocardial infarction, and ischemia of arms occurred. The results indicate that TEVAR combined with hybrid technique, chimney technique, and branched stent grafts is proven to be a technically feasible and effective treatment for acute complicated Stanford type B aortic dissection involving aortic arch in small cohort. Copyright © 2016 Elsevier Inc. All rights reserved.

Load dependence of the effective regurgitant orifice area in a sheep model of aortic regurgitation.

PubMed

Reimold, S C; Byrne, J G; Caguioa, E S; Lee, C C; Laurence, R G; Peigh, P S; Cohn, L H; Lee, R T

1991-10-01

Treatment of patients with aortic regurgitation with vasodilators reduces regurgitant volume, ventricular dilation and left ventricular mass. Although these effects are presumably due to afterload reduction, it is also possible that the aortic regurgitant orifice area is not constant. To test the latter hypothesis, aortic regurgitation was created in 10 open chest sheep by partial resection of the noncoronary leaflet under direct visualization. Regurgitant flow was measured with an aortic supravalvular electromagnetic probe; aortic and left ventricular pressures were measured with catheter-tipped micromanometer pressure transducers. The effective regurgitant orifice area was calculated by a modification of the continuity equation in a manner similar to the Gorlin equation. The regurgitant orifice area was measured three times: after aortic regurgitation was created, after mean arterial pressure was increased by 15 to 25 mm Hg with intravenous dopamine and after mean arterial pressure was reduced by 15 to 25 mm Hg with intravenous sodium nitroprusside. Comparison of regurgitant volumes and areas obtained after creation of aortic regurgitation and at the conclusion of the experiment in the absence of dopamine or sodium nitroprusside demonstrated no significant change over time. Dopamine administration was associated with an 86 +/- 81% increase in regurgitant volume (p less than 0.01) and a 38 +/- 44% increase in regurgitant orifice area (p less than 0.01). Sodium nitroprusside administration resulted in a 51 +/- 14% decrease in regurgitant volume (p less than 0.001) and a 28 +/- 21% reduction in regurgitant orifice area (p = 0.007). In this model of acute aortic regurgitation, the effective regurgitant orifice area was altered by increasing or decreasing the aortic transvalvular pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency aortic valve replacement and Caesarian section in a primigravida with severe aortic stenosis: a case report.

PubMed

Kochhar, Puneet K; Zutshi, V; Shamsunder, S; Batra, S; Ghosh, P

2011-01-01

Congenital bicuspid aortic valve with severe aortic stenosis (AS) is a rare condition (3-6% of patients with congenital heart disease). Pregnancy in these patients carries a high risk of maternal and fetal mortality. With advancing gestational age, these women may develop cardiac failure due to increased cardiorespiratory requirements. When medical therapy proves insufficient, cardiac surgery becomes mandatory to save the patient's life. Balloon valvuloplasty is only palliative treatment, the duration of benefit being only 6 months. Valve replacement is thus recommended. Cardiopulmonary bypass (CPB) surgery with valve replacement has been reported to carry a lower risk of maternal mortality (1.5-13%) but a very high fetal risk (16-40%). This paper reports the case of a 30-year-old primigravida with severe AS with bicuspid aortic valve and pulmonary congestion clinically uncontrolled, in whom CPB surgery and aortic valve replacement was performed as an emergency procedure, along with a lower segment Caesarian section. The outcome of unrelieved severe symptomatic AS in pregnancy is poor. Multidisciplinary management is important to avoid deterioration in cardiac performance in parturients with severe AS. CPB during pregnancy carries a high risk to the fetus. Therefore, open heart surgery during pregnancy should be advised only in extreme emergencies (ie, heart failure refractory to conventional therapy).

Testosterone deficiency: a determinant of aortic stiffness in men.

PubMed

Vlachopoulos, Charalambos; Ioakeimidis, Nikolaos; Miner, Martin; Aggelis, Athanassios; Pietri, Panagiota; Terentes-Printzios, Dimitrios; Tsekoura, Dorothea; Stefanadis, Christodoulos

2014-03-01

Low testosterone levels and increased aortic stiffness are predictors of cardiovascular events. The influence of androgen level on the age- and blood pressure-related increase in aortic stiffness is unknown. From January 2007 to June 2011 we enrolled 455 consecutive men with no evidence of cardiovascular disease from a large cohort followed in our Department for arterial function studies. Their total testosterone (TT) levels were measured and carotid-femoral pulse wave velocity (PWVc-f) was measured as an index of aortic stiffness. In multivariable analysis, PWVc-f values were inversely correlated to TT after adjustment for confounders (β = -0.365, P < 0.001). In younger age categories (<50 yrs and 50-59 yrs), patients with testosterone deficiency (TD) had higher blood pressure-adjusted PWVc-f (P < 0.001 and P = 0.005, respectively) compared to subjects with normal TT, indicating an "aging effect" of 10 years, whereas in older age categories such a difference was not observed. Furthermore, in men with a higher mean pressure (102-108 mmHg and >108 mmHg), patients with TD had higher age-adjusted PWVc-f (P < 0.001) compared to subjects with normal TT, indicating a synergistic unfavorable effect of testosterone deficiency and blood pressure on aortic stiffness. TT levels are independently associated with aortic stiffening. The effect of low testosterone concentration on aortic stiffness is more prominent in young men and in subjects with higher blood pressure levels. These findings identify testosterone as a marker of arterial damage with special emphasis on young and hypertensive individuals and support its role as predictor of events. Copyright © 2014. Published by Elsevier Ireland Ltd.

Abdominal Aortic Dissections

PubMed Central

Borioni, Raoul; Garofalo, Mariano; De Paulis, Ruggero; Nardi, Paolo; Scaffa, Raffaele; Chiariello, Luigi

2005-01-01

Isolated abdominal aortic dissections are rare events. Their anatomic and clinical features are different from those of atherosclerotic aneurysms. We report 4 cases of isolated abdominal aortic dissection that were successfully treated with surgical or endovascular intervention. The anatomic and clinical features and a review of the literature are also presented. PMID:15902826

Degree of fusiform dilatation of the proximal descending aorta in type B acute aortic dissection can predict late aortic events.

PubMed

Marui, Akira; Mochizuki, Takaaki; Koyama, Tadaaki; Mitsui, Norimasa

2007-11-01

Predicting the risk factors for late aortic events in patients with type B acute aortic dissection without complications may help to determine a therapeutic strategy for this disorder. We investigated whether late aortic events in type B acute aortic dissection can be predicted accurately by an index that expresses the degree of fusiform dilatation of the proximal descending aorta during the acute phase; this index can be calculated as follows: (maximum diameter of the proximal descending aorta)/(diameter of the distal aortic arch + diameter of the descending aorta at the pulmonary artery level). Patients with type B acute aortic dissection without complications (n = 141) were retrospectively analyzed to determine the predictors of late aortic events; these include aortic dilatation, rupture, refractory pain, organ ischemia, rapid aortic enlargement, and rapid enlargement of ulcer-like projections. The fusiform index in patients with late aortic events (0.59) was higher than that in patients without late aortic events (0.53, P < .01). Patients with a higher fusiform index exhibited aortic dilatation earlier than those with a lower fusiform index. By multivariate analysis, we conclude that the predominant independent predictors of late aortic events were a maximum aortic diameter of 40 mm or more, a patent false lumen, and a fusiform index of 0.64 or more (hazard ratios, 3.18, 2.64, and 2.73, respectively). The values of actuarial freedom from aortic events for patients with all 3 predictors at 1, 5, and 10 years were 22%, 17%, and 8%, respectively, whereas the values in those without these predictors were 97%, 94%, and 90%, respectively. The degree of fusiform dilatation of the proximal descending aorta, a patent false lumen, and a large aortic diameter can be predominant predictors of late aortic events in patients with type B acute aortic dissection. Patients with these predictors should be recommended to undergo early interventions (surgery or stent

Aortic valve replacement for papillary fibroelastoma.

PubMed

Arikan, Ali Ahmet; Omay, Oğuz; Aydın, Fatih; Kanko, Muhip; Gür, Sibel; Derviş, Emir; Yılmaz, Cansu Eda; Müezzinoğlu, Bahar

2017-06-01

Surgery is indicated for symptomatic patients with papillary fibroelastomas (PFE) on the aortic valve. The valve is commonly spared during tumor excision. Rarely, aortic valve replacement (AVR) is needed. We present a case requiring AVR for an aortic valve PFE and review the literature to determine the risk factors for failure of aortic valve-sparing techniques in patients with PFE. © 2017 Wiley Periodicals, Inc.

Lumbar muscle rhabdomyolysis after abdominal aortic surgery.

PubMed

Bertrand, M; Godet, G; Fléron, M H; Bernard, M A; Orcel, P; Riou, B; Kieffer, E; Coriat, P

1997-07-01

Lumbar muscle rhabdomyolysis has been very rarely reported after surgery. The aim of this study was to determine its incidence and main characteristics in a large population undergoing abdominal aortic surgery. Over a 21-mo period, 224 consecutive patients, 209 male and 15 female, mean age 65 +/- 10 yr, underwent abdominal aortic surgery (aortic aneurysm in 142 patients and occlusive aortic degenerative disease in 82 patients). Surgical incision was a midline incision with exaggerated hyperlordosis in 173 patients and a flank incision with a retroperitoneal approach in 51 patients. Postoperative rhabdomyolysis was diagnosed in 20 patients. In these patients, 9 (4%) experienced severe low back pain, and lumbar muscle rhabdomyolysis was confirmed by tomodensitometry (n = 6) or muscle biopsy (n = 3). The remaining 11 patients had lower limb muscle rhabdomyolysis. Rhabdomyolysis occurred after surgery of longer duration, which involved more frequent visceral artery reimplantation, with longer duration of aortic clamping and greater intraoperative bleeding. Lumbar rhabdomyolysis occurred in younger patients who were more frequently obese. On first postoperative day, the mean creatine kinase (CK) value was greater in lumbar rhabdomyolysis than in lower limb rhabdomyolysis (17,082 +/- 15,003 vs 3,313 +/- 3,120 IU/L, P < 0.05). Acute renal failure and postoperative death did not occur in patients with lumbar muscle rhabdomyolysis. Lumbar rhabdomyolysis was not a rare event after abdominal aortic surgery (4%). This syndrome was characterized by postoperative low back pain of unusual severity, which required analgesic therapy, and induced a very high increase in CK with typical findings at tomodensitometry or muscle biopsy but was not associated with postoperative renal failure.

Evaluation of eNOS gene polymorphisms in relation to BMD in postmenopausal women.

PubMed

Firat, Sibel Cubukcu; Cetin, Zafer; Samanci, Nehir; Aydin, Funda; Balci, Nilufer; Gungor, Firat; Firat, Mehmet Ziya; Luleci, Guven; Karauzum, Sibel Berker

2009-08-20

The aim of the present study was to evaluate the relations between T(-786)C and Glu298Asp polymorphisms of the endothelial nitric oxide synthase (eNOS) gene and BMD in postmenopausal Turkish women. The T(-786)C and Glu298Asp polymorphisms were genotyped by PCR-RFLP method in 311 postmenopausal osteoporotic women (OP) and in 305 age-matched postmenopausal females (CG) with normal BMD. None of the SNPs of the eNOS gene was significantly associated with BMD at the lumbar spine, femoral neck, Ward's triangle and femoral trochanter in the combined group. Mean BMD values were therefore found to be similar across the genotypes in postmenopausal Turkish women. However, there was a significant association between the T(-786)C polymorphism and BMD values at the lumbar spine in the normal control group (P=0.005), and at the femoral trochanter in the osteoporotic patients (P=0.046). The mean value of the lumbar spine BMD in the normal controls was significantly higher in women with the TC genotype of the T(-786)C polymorphism than in women with the TT genotype (P=0.0012). Women with the CC genotype of the T(-786)C polymorphism in the osteoporotic patients had significantly higher BMD value at the femoral trochanter than those with the TC (P=0.018) and TT genotypes (P=0.024). Frequencies of the TC heterozygotes for T(-786)C polymorphism were significantly higher among osteoporotic subjects than normal controls. Also, the CC and TT genotype frequencies of control group were significantly higher than those of the osteoporotic group at the femoral neck. We conclude that, although the biological role of the nitric oxide synthases is well established, our study does not suggest that eNOS gene polymorphisms, T(-786)C and Glu298Asp, are major contributors to adult bone mineral density in the postmenopausal Turkish women.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 +  T cells expressing TNFα and IFNγ.

PubMed

Kontos, Anna; Willoughby, Scott; van den Heuvel, Cameron; Kennedy, Declan; Martin, James; Hodge, Greg; Worthley, Matthew; Chin, Adelene Kaihui; Nelson, Adam; Teo, Karen; Baumert, Mathias; Pamula, Yvonne; Lushington, Kurt

2018-05-01

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8 + cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO 2 ) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO 2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO 2 nadir and an increased ascending aorta peak systolic

Aortic valve replacement using continuous suture technique in patients with aortic valve disease.

PubMed

Choi, Jong Bum; Kim, Jong Hun; Park, Hyun Kyu; Kim, Kyung Hwa; Kim, Min Ho; Kuh, Ja Hong; Jo, Jung Ku

2013-08-01

The continuous suture (CS) technique has several advantages as a method for simple, fast, and secure aortic valve replacement (AVR). We used a simple CS technique without the use of a pledget for AVR and evaluated the surgical outcomes. Between October 2007 and 2012, 123 patients with aortic valve disease underwent AVR alone (n=28) or with other concomitant cardiac procedures (n=95), such as mitral, tricuspid, or aortic surgery. The patients were divided into two groups: the interrupted suture (IS) group (n=47), in which the conventional IS technique was used, and the CS group (n=76), in which the simple CS technique was used. There were two hospital deaths (1.6%), which were not related to the suture technique. There were no significant differences in cardiopulmonary bypass time or aortic cross-clamp time between the two groups for AVR alone or AVR with concomitant cardiac procedures. In the IS group, two patients had prosthetic endocarditis and one patient experienced significant perivalvular leak. These patients underwent reoperations. In the CS group, there were no complications related to the surgery. Postoperatively, the two groups had similar aortic valve gradients. The simple CS method is useful and secure for AVR in patients with aortic valve disease, and it may minimize surgical complications, as neither pledgets nor braided sutures are used.

Updated clinical indications for transcatheter aortic valve implantation in patients with severe aortic stenosis: expert opinion of the Italian Society of Cardiology and GISE.

PubMed

Indolfi, Ciro; Bartorelli, Antonio L; Berti, Sergio; Golino, Paolo; Esposito, Giovanni; Musumeci, Giuseppe; Petronio, Sonia; Tamburino, Corrado; Tarantini, Giuseppe; Ussia, Gianpaolo; Vassanelli, Corrado; Spaccarotella, Carmen; Violini, Roberto; Mercuro, Giuseppe; Romeo, Francesco

2018-05-01

: The introduction of percutaneous treatment of severe aortic stenosis with transcatheter aortic valve implantation (TAVI) remains one of the greatest achievements of interventional cardiology. In fact, TAVI emerged as a better option than either medical therapy or balloon aortic valvuloplasty for patients who cannot undergo surgical aortic valve replacement (SAVR) or are at high surgical risk. Recently, increased operator experience and improved device systems have led to a worldwide trend toward the extension of TAVI to low-risk or intermediate-risk patients. In this expert opinion paper, we first discuss the basic pathophysiology of aortic stenosis in different settings then the key results of recent clinical investigations on TAVI in intermediate-risk aortic stenosis patients are summarized. Particular emphasis is placed on the results of the nordic aortic valve intervention, placement of aortic transcatheter valves (PARTNER) 2 and Surgical Replacement and Transcatheter Aortic Valve Implantation Randomized trials. The PARTNER 2 was the first large randomized trial that evaluated the outcome of TAVI in patients at intermediate risk. The PARTNER 2 data demonstrated that TAVI is a feasible and reasonable alternative to surgery in intermediate-risk patients (Society of Thoracic Surgeons 4-8%), especially if they are elderly or frail. There was a significant interaction between TAVI approach and mortality, with transfemoral TAVI showing superiority over SAVR. Moreover, we examine the complementary results of the recently concluded Surgical Replacement and Transcatheter Aortic Valve Implantation trial. This prospective randomized trial demonstrated that TAVI is comparable with surgery (primary end point 12.6% in the TAVI group vs. 14.0% in the SAVR group) in severe aortic stenosis patients deemed to be at intermediate risk. We review the most relevant clinical evidence deriving from nonrandomized studies and meta-analyses. Altogether, clinical outcome available data

Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis.

PubMed

Capoulade, Romain; Teoh, Jonathan G; Bartko, Philipp E; Teo, Eliza; Scholtz, Jan-Erik; Tastet, Lionel; Shen, Mylene; Mihos, Christos G; Park, Yong H; Garcia, Julio; Larose, Eric; Isselbacher, Eric M; Sundt, Thoralf M; MacGillivray, Thomas E; Melnitchouk, Serguei; Ghoshhajra, Brian B; Pibarot, Philippe; Hung, Judy

2018-05-01

The aim of this study was to examine the association between abnormal morphology of the proximal aorta and aortic stenosis (AS) progression rate. The main hypothesis was that morphologic changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), result in increased biomechanical stresses and contribute to calcification and progression of AS. Between 2010 and 2012, 426 patients with mild to moderate AS were included in this study. Proximal aortic dimensions were measured at three different levels (i.e., sinus of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending aorta/STJ ratios were used to determine degree of aortic deformity. AS progression rate was assessed by annualized increase in mean gradient (median follow-up time, 3.1 years; interquartile range, 2.6-3.9 years). The degree of aortic flow turbulence was examined in 18 matched patients with and without STJ effacement using cardiac magnetic resonance phase-contrast imaging. Patients' mean age was 71 ± 13 years, and 64% were men. Patients with low ratios had greater AS progression (P < .05). After comprehensive adjustment, sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were independently associated with greater AS progression rate. Compared with patients without STJ effacement, those with effacement of the STJ had higher degrees of aortic flow turbulence (24.4% vs 17.2%, P = .038). Effacement of the STJ is independently associated with greater AS progression, regardless of arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients with abnormal proximal aortic geometry had disturbed aortic flow patterns. These findings suggest an interrelation between proximal aorta morphology and stenosis progression. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Thoracic aortic aneurysms and dissections: endovascular treatment.

PubMed

Baril, Donald T; Cho, Jae S; Chaer, Rabih A; Makaroun, Michel S

2010-01-01

The treatment of thoracic aortic disease has changed radically with the advances made in endovascular therapy since the concept of thoracic endovascular aortic repair was first described 15 years ago. Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies, including industry-sponsored and single-institution reports, have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease. This review examines the currently available thoracic endografts, preoperative planning for thoracic endovascular aortic repair, and outcomes of thoracic endovascular aortic repair for the treatment of both thoracic aortic aneurysms and type B aortic dissections. Mt Sinai J Med 77:256-269, 2010. (c) 2010 Mount Sinai School of Medicine.

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses.

PubMed

Schuhbaeck, Annika; Weingartner, Christina; Arnold, Martin; Schmid, Jasmin; Pflederer, Tobias; Marwan, Mohamed; Rixe, Johannes; Nef, Holger; Schneider, Christian; Lell, Michael; Uder, Michael; Ensminger, Stephan; Feyrer, Richard; Weyand, Michael; Achenbach, Stephan

2015-07-01

The geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. Eighty consecutive patients with severe aortic valve stenosis (mean age 82 ± 6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. Aortic annulus eccentricity was reduced in patients after TAVI (0.21 ± 0.06 vs. 0.08 ± 0.06, p<0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06 ± 0.05 vs. 0.15 ± 0.07, p<0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. Patients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetics Home Reference: supravalvular aortic stenosis

MedlinePlus

... Twitter Home Health Conditions Supravalvular aortic stenosis Supravalvular aortic stenosis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Supravalvular aortic stenosis (SVAS) is a heart defect that develops before ...

Aortic annulus and ascending aorta: comparison of preoperative and periooperative measurement in patients with aortic stenosis.

PubMed

Smíd, Michal; Ferda, Jirí; Baxa, Jan; Cech, Jakub; Hájek, Tomás; Kreuzberg, Boris; Rokyta, Richard

2010-04-01

Precise determination of the aortic annulus size constitutes an integral part of the preoperative evaluation prior to aortic valve replacement. It enables the estimation of the size of prosthesis to be implanted. Knowledge of the size of the ascending aorta is required in the preoperative analysis and monitoring of its dilation enables the precise timing of the operation. Our goal was to compare the precision of measurement of the aortic annulus and ascending aorta using magnetic resonance (MR), multidetector-row computed tomography (MDCT), transthoracic echocardiography (TTE), and transoesophageal echocardiography (TEE) in patients with degenerative aortic stenosis. A total of 15 patients scheduled to have aortic valve replacement were enrolled into this prospective study. TTE was performed in all patients and was supplemented with TEE, CT and MR in the majority of patients. The values obtained were compared with perioperative measurements. For the measurement of aortic annulus, MR was found to be the most precise technique, followed by MDCT, TTE, and TEE. For the measurement of ascending aorta, MR again was found to be the most precise technique, followed by MDCT, TEE, and TTE. In our study, magnetic resonance was found to be the most precise technique for the measurement of aortic annulus and ascending aorta in patients with severe degenerative aortic stenosis. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Surgical Treatment of Synchronous Type B Acute Aortic Dissection and Abdominal Aortic Aneurysm.

PubMed

Bellosta, Raffaello; Gelpi, Guido; Lomazzi, Chiara; Romagnoni, Claudia; Castelli, Patrizio; Trimarchi, Santi; Piffaretti, Gabriele

2018-05-01

We report the results of the operative treatment of synchronous type B acute aortic dissection (TBAAD) and infrarenal abdominal aortic aneurysm (AAA). It is an observational, descriptive multicenter case series. Inclusion criterion was patients with diagnosis of TBAAD and AAA detected synchronously for the first time at clinical onset of dissection. Follow-up imaging protocol included triple-phase spiral/computed tomography angiography performed at 1, 6, and 12 months after thoracic endovascular aortic repair (TEVAR), and annually thereafter. Major end points were perioperative mortality and long-term survival, freedom from aortic events, and freedom from reintervention. We identified and treated 15 cases. All TBAADs were treated by TEVAR in the acute phase: infrarenal aortic repair was performed with stent graft (SG) in 10 (66.7%) patients, with open repair in 5 (33.3%). Overall, staged repair was used in 11 (73.3%) patients. Mean descending aortic endovascular length coverage was 21 cm ± 7 (range, 10-35; interquartile range [IQR], 150-265). Overall, early perioperative mortality occurred in 1 (6.7%) patient. Median radiologic follow-up was 48 months (range, 6-120; IQR, 36-67). During the follow-up, TEVAR-related mortality was not observed. Aortic remodeling after TEVAR was obtained in 12 (85.7%) patients; abdominal sac shrinkage after SG was obtained in 8 (80.0%) patients. Freedom from aortic event rate was 79% ± 10 (95% confidence interval [CI]: 53.1-92.6) at 1 year and 64% ± 13 (95% CI: 38.1-83.5) at 5 year. Freedom from reintervention rate at 1 and 5 year was 85% ± 10 (95% CI: 57.8-95.7). In our experience, the association of TBAAD and AAA was a rare finding. Because of the lack of available evidence to opt for a single intervention or a staged approach, selective approach with TEVAR and endovascular/open conventional treatment of the abdominal aorta yielded satisfactory results at midterm follow-up. Copyright © 2018 Elsevier Inc. All rights

Sex differences in aortic valve calcification measured by multidetector computed tomography in aortic stenosis.

PubMed

Aggarwal, Shivani R; Clavel, Marie-Annick; Messika-Zeitoun, David; Cueff, Caroline; Malouf, Joseph; Araoz, Philip A; Mankad, Rekha; Michelena, Hector; Vahanian, Alec; Enriquez-Sarano, Maurice

2013-01-01

Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm(2); mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC-AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P=0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm(2)/m(2); P=0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P<0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P<0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P<0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r>0.67; P<0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P≤0.01). In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.