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  1. Reversal of SIN-1-induced eNOS dysfunction by the spin trap, DMPO, in bovine aortic endothelial cells via eNOS phosphorylation

    PubMed Central

    Das, Amlan; Gopalakrishnan, Bhavani; Druhan, Lawrence J; Wang, Tse-Yao; De Pascali, Francesco; Rockenbauer, Antal; Racoma, Ira; Varadharaj, Saradhadevi; Zweier, Jay L; Cardounel, Arturo J; Villamena, Frederick A

    2014-01-01

    Background and Purpose Nitric oxide (NO) derived from eNOS is mostly responsible for the maintenance of vascular homeostasis and its decreased bioavailability is characteristic of reactive oxygen species (ROS)-induced endothelial dysfunction (ED). Because 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), a commonly used spin trap, can control intracellular nitroso-redox balance by scavenging ROS and donating NO, it was employed as a cardioprotective agent against ED but the mechanism of its protection is still not clear. This study elucidated the mechanism of protection by DMPO against SIN-1-induced oxidative injury to bovine aortic endothelial cells (BAEC). Experimental Approach BAEC were treated with SIN-1, as a source of peroxynitrite anion (ONOO−), and then incubated with DMPO. Cytotoxicity following SIN-1 alone and cytoprotection by adding DMPO was assessed by MTT assay. Levels of ROS and NO generation from HEK293 cells transfected with wild-type and mutant eNOS cDNAs, tetrahydrobiopterin bioavailability, eNOS activity, eNOS and Akt kinase phosphorylation were measured. Key Results Post-treatment of cells with DMPO attenuated SIN-1-mediated cytotoxicity and ROS generation, restoration of NO levels via increased in eNOS activity and phospho-eNOS levels. Treatment with DMPO alone significantly increased NO levels and induced phosphorylation of eNOS Ser1179 via Akt kinase. Transfection studies with wild-type and mutant human eNOS confirmed the dual role of eNOS as a producer of superoxide anion (O2−) with SIN-1 treatment, and a producer of NO in the presence of DMPO. Conclusion and Implications Post-treatment with DMPO of oxidatively challenged cells reversed eNOS dysfunction and could have pharmacological implications in the treatment of cardiovascular diseases. PMID:24405159

  2. C. pneumoniae disrupts eNOS trafficking and impairs NO production in human aortic endothelial cells.

    PubMed

    Mueller, Konrad E; Wolf, Katerina

    2015-01-01

    Endothelial nitric oxide synthase (eNOS) generated NO plays a crucial physiological role in the regulation of vascular tone. eNOS is a constitutively expressed synthase whose enzymatic function is regulated by dual acylation, phosphorylation, protein-protein interaction and subcellular localization. In endothelial cells, the enzyme is primarily localized to the Golgi apparatus (GA) and the plasma membrane where it binds to caveolin-1. Upon stimulation, the enzyme is translocated from the plasma membrane to the cytoplasm where it generates NO. When activation of eNOS ceases, the majority of the enzyme is recycled back to the membrane fraction. An inability of eNOS to cycle between the cytosol and the membrane leads to impaired NO production and vascular dysfunction. Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that primarily infects epithelial cells of the human respiratory tract, but unlike any other chlamydial species, C. pneumoniae displays tropism toward atherosclerotic tissues. In this study, we demonstrate that C. pneumoniae inclusions colocalize with eNOS, and the microorganism interferes with trafficking of the enzyme from the GA to the plasma membrane in primary human aortic endothelial cells. This mislocation of eNOS results in significant inhibition of NO release by C. pneumoniae-infected cells. Furthermore, we show that the distribution of eNOS in C. pneumoniae-infected cells is altered due to an intimate association of the Golgi complex with chlamydial inclusions rather than by direct interaction of the enzyme with the chlamydial inclusion membrane.

  3. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC

    SciTech Connect

    Murakami, Hisashi; Murakami, Ryuichiro . E-mail: ryuichi@med.nagoya-u.ac.jp; Kambe, Fukushi; Cao, Xia; Takahashi, Ryotaro; Asai, Toru; Hirai, Toshihisa; Numaguchi, Yasushi; Okumura, Kenji; Seo, Hisao; Murohara, Toyoaki

    2006-03-24

    Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.

  4. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    PubMed Central

    Du, Xueliang; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals previously implicated in hyperglycemia-induced vascular damage and inactivated 2 important antiatherogenic enzymes, prostacyclin synthase and eNOS. In 2 nondiabetic rodent models — insulin-resistant, obese Zucker (fa/fa) rats and high-fat diet–induced insulin-resistant mice — inactivation of prostacyclin synthase and eNOS was prevented by inhibition of FFA release from adipose tissue; by inhibition of the rate-limiting enzyme for fatty acid oxidation in mitochondria, carnitine palmitoyltransferase I; and by reduction of superoxide levels. These studies identify what we believe to be a novel mechanism contributing to the accelerated atherogenesis and increased cardiovascular disease risk occurring in people with insulin resistance. PMID:16528409

  5. Recoupling of eNOS with Folic Acid Prevents Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Apolipoprotein E Null Mice

    PubMed Central

    Siu, Kin Lung; Miao, Xiao Niu; Cai, Hua

    2014-01-01

    We have previously shown that eNOS uncoupling mediates abdominal aortic aneurysm (AAA) formation in hph-1 mice. In the present study we examined whether recoupling of eNOS prevents AAA formation in a well-established model of Angiotensin II-infused apolipoprotein E (apoE) null mice by targeting some common pathologies of AAA. Infusion of Ang II resulted in a 92% incidence rate of AAA in the apoE null animals. In a separate group, animals were treated orally with folic acid (FA), which is known to recouple eNOS through augmentation of dihydrofolate reductase (DHFR) function. This resulted in a reduction of AAA rate to 19.5%. Imaging with ultrasound showed that FA markedly inhibited expansion of abdominal aorta. FA also abolished elastin breakdown and macrophage infiltration in the AAA animals. The eNOS uncoupling activity, assessed by L-NAME-sensitive superoxide production, was minimal at baseline but greatly exaggerated with Ang II infusion, which was completely attenuated by FA. This was accompanied by markedly improved tetrahydrobiopterin and nitric oxide bioavailability. Furthermore, the expression and activity of DHFR was decreased in Ang II-infused apoE null mice specifically in the endothelial cells, while FA administration resulted in its recovery. Taken together, these data further establish a significant role of uncoupled eNOS in mediating AAA formation, and a universal efficacy of FA in preventing AAA formation via restoration of DHFR to restore eNOS function. PMID:24558445

  6. Changes in eNOS phosphorylation contribute to increased arteriolar NO release during juvenile growth

    PubMed Central

    Kang, Lori S.; Nurkiewicz, Timothy R.; Wu, Guoyao

    2012-01-01

    Nitric oxide (NO) mediates a major portion of arteriolar endothelium-dependent dilation in adults, but indirect evidence has suggested that NO contributes minimally to these responses in the young. Isolated segments of arterioles were studied in vitro to verify this age-related increase in NO release and investigate the mechanism by which it occurs. Directly measured NO release induced by ACh or the Ca2+ ionophore A-23187 was five- to sixfold higher in gracilis muscle arterioles from 42- to 46-day-old (juvenile) rats than in those from 25- to 28-day-old (weanling) rats. There were no differences between groups in arteriolar endothelial NO synthase (eNOS) expression or tetrahydrobiopterin levels, and arteriolar l-arginine levels were lower in juvenile vessels than in weanling vessels (104 ± 6 vs.126 ± 3 pmol/mg). In contrast, agonist-induced eNOS Thr495 dephosphorylation and eNOS Ser1177 phosphorylation (events required for maximal activity) were up to 30% and 65% greater, respectively, in juvenile vessels. Juvenile vessels did not show increased expression of enzymes that mediate these events [protein phosphatases 1 and 2A and PKA and PKB (Akt)] or heat shock protein 90, which facilitates Ser1177 phosphorylation. However, agonist-induced colocalization of heat shock protein 90 with eNOS was 34–66% greater in juvenile vessels than in weanling vessels, and abolition of this difference with geldanamycin also abolished the difference in Ser1177 phosphorylation between groups. These findings suggest that growth-related increases in arteriolar NO bioavailability may be due at least partially to changes in the regulation of eNOS phosphorylation and increased signaling activity, with no change in the abundance of eNOS signaling proteins. PMID:22140037

  7. Monomeric adiponectin increases cell viability in porcine aortic endothelial cells cultured in normal and high glucose conditions: Data on kinases activation.

    PubMed

    Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

    2016-09-01

    We found that monomeric adiponectin was able to increase cell viability in porcine aortic endothelial cells (PAE) cultured both in normal and high glucose condition. Moreover, in normal glucose condition monomeric adiponectin increased p38MAPK, Akt, ERK1/2 and eNOS phosphorylation in a dose- and time-dependent way. Also in high glucose condition monomeric adiponectin increased eNOS and above kinases phosphorylation with similar patterns but at lower extent. For interpretation of the data presented in this article, please see the research article "Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions" (Grossini et al., in press) [1]. PMID:27583345

  8. VEGF, eNOS, and ABCB1 genetic polymorphisms may increase the risk of osteonecrosis of the femoral head.

    PubMed

    Zhou, Z C; Gu, S Z; Wu, J; Liang, Q W

    2015-01-01

    We investigated the associations between vascular endothelial growth factors (VEGF), endothelial nitric oxide synthase (eNOS), and ATP-binding cassette subfamily B member 1 transporter (ABCB1) polymorphisms and the risk of osteonecrosis of the femoral head (ONFH). Published studies were reviewed and analyzed based on predefined selection criteria. The strength of the association between VEGF, eNOS, and ABCB1 polymorphisms and ONFH risk was evaluated based on the odds ratio with corresponding 95%CIs. Meta-analysis was performed using the Comprehensive Meta-analysis 2.0 software. A total of 135 relevant articles were retrieved, of which 10 studies met the selection criteria, and included a total of 1025 patients with ONFH and 1730 healthy controls. The meta-analysis study results revealed that the VEGF rs2010963 G>C polymorphism increased the risk of ONFH, while the VEGF rs2010963 G>C and ABCB1 rs1045642 C>T polymorphisms increased the risk of ONFH under the allele model. In conclusion, the VEGF, eNOS, and ABCB1 polymorphisms may contribute to ONFH, but further studies including larger sample sizes are needed to confirm the results. PMID:26535684

  9. Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression

    PubMed Central

    Uğurel, Seda Sultan; Kuşçu, Nilay; Özenci, Çiler Çelik; Dalaklıoğlu, Selvinaz; Taşatargil, Arda

    2016-01-01

    Background: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. Aims: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. Study Design: Animal experiment. Methods: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. Results: LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. Conclusion: The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity. PMID:27403381

  10. Biglycan deficiency: increased aortic aneurysm formation and lack of atheroprotection

    PubMed Central

    Tang, Tao; Thompson, Joel C.; Wilson, Patricia G.; Yoder, Meghan H.; Müeller, Julia; Fischer, Jens W.; Jon Williams, Kevin; Tannock, Lisa R.

    2014-01-01

    Background Proteoglycans of the arterial wall play a critical role in vascular integrity and the development of atherosclerosis owing to their ability to organize extracellular matrix molecules and to bind and retain atherogenic apolipoprotein (apo)-B containing lipoproteins. Prior studies have suggested a role for biglycan in aneurysms and in atherosclerosis. Angiotensin II (angII) infusions into mice have been shown to induce abdominal aortic aneurysm development, increase vascular biglycan content, increase arterial retention of lipoproteins, and accelerate atherosclerosis. Objective The goal of this study was to determine the role of biglycan in angII-induced vascular diseases. Design Biglycan-deficient or biglycan wildtype mice crossed to LDL receptor deficient (Ldlr−/−)mice (C57BL/6 background) were infused with angII (500 or 1000 ng/kg/min) or saline for 28 days while fed on normal chow, then pumps were removed, and mice were switched to an atherogenic Western diet for 6 weeks. Results During angII infusions, biglycan-deficient mice developed abdominal aortic aneurysms, unusual descending thoracic aneurysms, and a striking mortality caused by aortic rupture (76% for males and 48% for females at angII 1000 ng/kg/min). Histological analyses of non-aneurysmal aortic segments from biglycan-deficient mice revealed a deficiency of dense collagen fibers and the aneurysms demonstrated conspicuous elastin breaks. AngII infusion increased subsequent atherosclerotic lesion development in both biglycan-deficient and biglycan wildtype mice. However, the biglycan genotype did not affect atherosclerotic lesion area induced by the Western diet after treatment with angII. Biglycan-deficient mice exhibited significantly increased vascular perlecan content compared to biglycan wildtype mice. Analyses of the atherosclerotic lesions demonstrated that vascular perlecan co-localized with apoB, suggesting that increased perlecan compensated for biglycan deficiency in terms of

  11. NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms?

    PubMed Central

    Villela-Nogueira, Cristiane A.; Leite, Nathalie C.; Cardoso, Claudia R. L.; Salles, Gil F.

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide. Liver inflammation and fibrosis related to NAFLD contribute to disease progression and increasing liver-related mortality and morbidity. Increasing data suggest that NAFLD may be linked to atherosclerotic vascular disease independent of other established cardiovascular risk factors. Central arterial stiffness has been recognized as a measure of cumulative cardiovascular risk marker load, and the measure of carotid-femoral pulse wave velocity (cf-PWV) is regarded as the gold standard assessment of aortic stiffness. It has been shown that increased aortic stiffness predicts cardiovascular morbidity and mortality in several clinical settings, including type 2 diabetes mellitus, a well-known condition associated with advanced stages of NAFLD. Furthermore, recently-published studies reported a strong association between NAFLD and increased arterial stiffness, suggesting a possible link in the pathogenesis of atherosclerosis and NAFLD. We sought to review the published data on the associations between NAFLD and aortic stiffness, in order to better understand the interplay between these two conditions and identify possible common physiopathological mechanisms. PMID:27104526

  12. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru; Niwa, Koichi; Hattori, Yuichi; Kondo, Takashi; Inanami, Osamu

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  13. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    PubMed Central

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Materials and Methods: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. Results: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. Conclusion: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance. PMID:27114795

  14. Cholesterol depletion increases membrane stiffness of aortic endothelial cells.

    PubMed

    Byfield, Fitzroy J; Aranda-Espinoza, Helim; Romanenko, Victor G; Rothblat, George H; Levitan, Irena

    2004-11-01

    This study has investigated the effect of cellular cholesterol on membrane deformability of bovine aortic endothelial cells. Cellular cholesterol content was depleted by exposing the cells to methyl-beta-cyclodextrin or enriched by exposing the cells to methyl-beta-cyclodextrin saturated with cholesterol. Control cells were treated with methyl-beta-cyclodextrin-cholesterol at a molar ratio that had no effect on the level of cellular cholesterol. Mechanical properties of the cells with different cholesterol contents were compared by measuring the degree of membrane deformation in response to a step in negative pressure applied to the membrane by a micropipette. The experiments were performed on substrate-attached cells that maintained normal morphology. The data were analyzed using a standard linear elastic half-space model to calculate Young elastic modulus. Our observations show that, in contrast to the known effect of cholesterol on membrane stiffness of lipid bilayers, cholesterol depletion of bovine aortic endothelial cells resulted in a significant decrease in membrane deformability and a corresponding increase in the value of the elastic coefficient of the membrane, indicating that cholesterol-depleted cells are stiffer than control cells. Repleting the cells with cholesterol reversed the effect. An increase in cellular cholesterol to a level higher than that of normal cells, however, had no effect on the elastic properties of bovine aortic endothelial cells. We also show that although cholesterol depletion had no apparent effect on the intensity of F-actin-specific fluorescence, disrupting F-actin with latrunculin A abrogated the stiffening effect. We suggest that cholesterol depletion increases the stiffness of the membrane by altering the properties of the submembrane F-actin and/or its attachment to the membrane.

  15. Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo.

    PubMed

    Mahn, Katharina; Borrás, Consuelo; Knock, Greg A; Taylor, Paul; Khan, Imran Y; Sugden, David; Poston, Lucilla; Ward, Jeremy P T; Sharpe, Richard M; Viña, Jose; Aaronson, Philip I; Mann, Giovanni E

    2005-10-01

    Epidemiological evidence suggests that populations consuming large amounts of soy protein have a reduced incidence of coronary heart disease (1-5). The cardiovascular risks associated with conventional hormone replacement therapy in postmenopausal women (5-7) have precipitated a search for alternative estrogen receptor modulators. Here we report that long-term feeding of rats with a soy protein-rich (SP) diet during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure in vivo measured by radiotelemetry in aged male offspring. Improved vascular reactivity in animals fed an SP diet was paralleled by increased mitochondrial glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase. Reduced eNOS and antioxidant gene expression, impaired endothelial function, and elevated blood pressure in animals fed a soy-deficient diet was reversed after refeeding them an SP diet for 6 months. Our findings suggest that an SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart disease.

  16. Sustained hypertension despite endothelial-specific eNOS rescue in eNOS-deficient mice.

    PubMed

    Suvorava, Tatsiana; Stegbauer, Johannes; Thieme, Manuel; Pick, Stephanie; Friedrich, Sebastian; Rump, Lars C; Hohlfeld, Thomas; Kojda, Georg

    2015-03-13

    The aim of the study was to evaluate the possible contribution of non-endothelial eNOS to the regulation of blood pressure (BP). To accomplish this, a double transgenic strain expressing eNOS exclusively in the vascular endothelium (eNOS-Tg/KO) has been generated by endothelial-specific targeting of bovine eNOS in eNOS-deficient mice (eNOS-KO). Expression of eNOS was evaluated in aorta, myocardium, kidney, brain stem and skeletal muscle. Organ bath studies revealed a complete normalization of aortic reactivity to acetylcholine, phenylephrine and the NO-donors in eNOS-Tg/KO. Function of eNOS in resistance arteries was demonstrated by acute i.v. infusion of acetylcholine and the NOS-inhibitor L-NAME. Acetylcholine decreased mean arterial pressure in all strains but eNOS-KO responded significantly less sensitive as compared eNOS-Tg/KO and C57BL/6. Likewise, acute i.v. L-NAME application elevated mean arterial pressure in C57BL/6 and eNOS-Tg/KO, but not in eNOS-KO. In striking contrast to these findings, mean, systolic and diastolic BP in eNOS-Tg/KO remained significantly elevated and was similar to values of eNOS-KO. Chronic oral treatment with L-NAME increased BP to the level of eNOS-KO only in C57BL/6, but had no effect on hypertension in eNOS-KO and eNOS-Tg/KO. Taken together, functional reconstitution of eNOS in the vasculature of eNOS-KO not even partially lowered BP. These data suggest that the activity of eNOS expressed in non-vascular tissue might play a role in physiologic BP regulation. PMID:25680465

  17. 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.

  18. Extract from Ribes nigrum leaves in vitro activates nitric oxide synthase (eNOS) and increases CD39 expression in human endothelial cells.

    PubMed

    Luzak, Boguslawa; Boncler, Magdalena; Rywaniak, Joanna; Dudzinska, Dominika; Rozalski, Marek; Krajewska, Urszula; Balcerczak, Ewa; Podsedek, Anna; Redzynia, Malgorzata; Watala, Cezary

    2014-12-01

    The aim of the present study was to evaluate whether blackcurrant leaf extract (BLE) modulates endothelium antithrombotic function, namely increases the expression/activity of ADPase (CD39) and augments the production of nitric oxide in human umbilical vein endothelial cells (HUVEC). It was found that BLE with proanthocyanidins (60 % of the total polyphenol content) increased the CD39-positive endothelial cell fraction (up to 10 % for 2.5 μg/ml, and up to 33 % for 15 μg/ml, p < 0.05 or less) in a concentration-dependent manner, and enhanced endothelial nitric oxide synthase (eNOS) activation (T495 phosphorylation decreased by 31 ± 6 % for 2.5 μg/ml and 48 ± 6 % for 15 μg/ml; S1177 phosphorylation increased by 13 ± 3 % for 2.5 μg/ml and 18 ± 7 % for 15 μg/ml, compared to untreated cells, p < 0.05 or less). Additionally, incubation for 24 or 48 h with BLE at a lower range of polyphenol concentrations, significantly increased cell viability with a maximal effect at 2.5 μg/ml (viability increased by 24.8 ± 1.0 % for 24 h and by 32.5 ± 2.7 % for 48-h time incubation, p < 0.0001). The increased CD39 expression and the increased eNOS activation in HUVEC can be regarded as the beneficial markers of the improvement of antiplatelet action of endothelial cells. Unexpectedly, these assumptions were not confirmed in the experimental model of platelet-endothelial cell interactions. These observations lead to the conclusion that BLE may improve endothelial cell viability at low physiological concentrations without affecting the antiplatelet action of endothelium. PMID:25407137

  19. Geometrical factors as predictors of increased growth rate or increased rupture risk in small aortic aneurysms.

    PubMed

    Georgakarakos, Efstratios; Ioannou, Christos V

    2012-07-01

    Abdominal Aortic Aneurysms (AAAs) are focal dilation of the aorta that can lead to excessive enlargement and rupture over time. Current practice suggests intervention when the maximum diameter exceeds 5.5 cm, since in this diameter range the annual rupture risk outweighs the operative mortality. However, small AAA (<5.5 cm), though infrequently, may rupture or produce symptoms. Evidence from large randomized studies of small AAAs support the heterogeneity in patterns of growth and rupture potential among small AAAs. Elevated wall stress values have been implicated in AAAs rupture and rapid enlargement. Additionally, many studies have identified a strong correlation between certain geometric factors and elevated stress values. In this article we discuss the possibility that geometrical factors may have a predictive value to identify those small AAAs that have an increased risk of rupture or growth rate either during initial examination or during follow-up, making them amenable for early repair. PMID:22541859

  20. Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells

    PubMed Central

    López-Ongil, S; Hernández-Perera, O; Navarro-Antolín, J; Pérez de Lema, G; Rodríguez-Puyol, M; Lamas, S; Rodríguez-Puyol, D

    1998-01-01

    Cyclosporine A (CsA) increases eNOS mRNA expression in bovine cultured aortic endothelial cells (BAEC). As some effects of CsA may be mediated by reactive oxygen species (ROS), present experiments were devoted to test the hypothesis that the CsA-induced eNOS up-regulation could be dependent on an increased synthesis of ROS.CsA induced a dose-dependent increase of ROS synthesis, with the two fluorescent probes used, DHR123 (CsA 1 μM: 305±7% over control) and H2DCFDA (CsA 1 μM: 178±6% over control).Two ROS generating systems, xanthine plus xanthine oxidase (XXO) and glucose oxidase (GO), increased the expression of eNOS mRNA in BAEC, an effect which was maximal after 8 h of incubation (XXO: 168±21% of control values. GO: 208±18% of control values). The ROS-dependent increased eNOS mRNA expression was followed by an increase in eNOS activity.The effect of CsA on eNOS mRNA expression was abrogated by catalase, and superoxide dismutase (SOD). In contrast, the antioxidant PDTC augmented eNOS mRNA expression, both in basal conditions and in the presence of CsA.The potential participation of the transcription factor AP-1 was explored. Electrophoretic mobility shift assays were consistent with an increase in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase.The present results support a role for ROS, particularly superoxide anion and hydrogen peroxide, as mediators of the CsA-induced eNOS mRNA up-regulation. Furthermore, they situate ROS as potential regulators of gene expression in endothelial cells, both in physiological and pathophysiological situations. PMID:9647467

  1. Mechanisms and Consequences of eNOS Dysfunction in Hypertension

    PubMed Central

    Li, Qiang; Yon, Ji-Youn; Cai, Hua

    2016-01-01

    Reduced nitric oxide (NO) bioavailability contributes to endothelial dysfunction and hypertension. The endothelial isoform of NO synthase (eNOS) is responsible for the production of NO within endothelium. Loss of eNOS cofactor tetrahydrobiopterin to initial increase in oxidative stress leads to uncoupling of eNOS, in which the enzyme produces superoxide anion rather than NO, further substantiating oxidative stress to induce vascular pathogenesis. The current review focuses on recent advances on the molecular mechanisms and consequences of eNOS dysfunction in hypertension, and potential novel therapeutic strategies restoring eNOS function to treat hypertension. PMID:25882860

  2. Aortic endothelium in HIV-1 infection: chronic injury, activation, and increased leukocyte adherence.

    PubMed Central

    Zietz, C.; Hotz, B.; Stürzl, M.; Rauch, E.; Penning, R.; Löhrs, U.

    1996-01-01

    Clinical and serological studies provide evidence for a pathogenetically relevant vasculopathy in acquired immune deficiency syndrome (AIDS); however, the morphological status of the endothelium under conditions of human immunodeficiency virus (HIV)-1 infection is only sparsely documented. In this study we adapted an en face preparation technique of endothelium for use in immunohistochemistry and investigated the aortic endothelium of pre-AIDS and AIDS patients (n = 32) in comparison with an HIV-negative group (n = 17). The control group showed a regular pattern of evenly distributed aortic endothelial cells, whereas the endothelial cell pattern in the HIV-1-infected patients was clearly disturbed. Simultaneously, the degree of leukocyte adherence on the aortic endothelium increased significantly. These changes were accompanied by an up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (ELAM-1). The endothelium turnover increased, and one-half of the HIV-1-infected patients exhibited HLA-DR (major histocompatibility complex class II) antigen in the aortic endothelium. Our results provide evidence for a profound and repeated injury with regeneration and activation of the endothelium in HIV-1 infection. Injury as well as activation of the endothelium impairs its normal regulatory properties. This could have consequences for the maintenance of the blood-brain barrier; it might influence the immunologically important interaction of the endothelium with T cells; and it might trigger Kaposi's sarcoma. Images Figure 1 Figure 2 Figure 3 PMID:8952525

  3. Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population.

    PubMed

    Mayer, O; Seidlerová, J; Wohlfahrt, P; Filipovský, J; Vaněk, J; Cífková, R; Windrichová, J; Topolčan, O; Knapen, M H J; Drummen, N E A; Vermeer, C

    2016-07-01

    Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.

  4. Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population.

    PubMed

    Mayer, O; Seidlerová, J; Wohlfahrt, P; Filipovský, J; Vaněk, J; Cífková, R; Windrichová, J; Topolčan, O; Knapen, M H J; Drummen, N E A; Vermeer, C

    2016-07-01

    Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries. PMID:26016598

  5. Aortic Valve Cyclic Stretch Causes Increased Remodeling Activity and Enhanced Serotonin Receptor Responsiveness

    PubMed Central

    Balachandran, Kartik; Bakay, Marina A.; Connolly, Jeanne M.; Zhang, Xuemei; Yoganathan, Ajit P.; Levy, Robert J.

    2011-01-01

    Background Increased serotonin(5HT) receptor(5HTR) signaling has been associated with cardiac valvulopathy. Prior cell culture studies of 5HTR signaling in heart valve interstitial cells have provided mechanistic insights concerning only static conditions. We investigated the hypothesis that aortic valve biomechanics participate in the regulation of both 5HTR expression and inter-related extracellular matrix remodeling events. Methods The effects of cyclic-stretch on aortic valve 5HTR, expression, signaling and extracellular matrix remodeling were investigated using a tensile stretch bioreactor in studies which also compared the effects of adding 5HT and/or the 5HT-transporter inhibitor, Fluoxetine. Results Cyclic-stretch alone increased both proliferation and collagen in porcine aortic valve cusp samples. However, with cyclic-stretch, unlike static conditions, 5HT plus Fluoxetine caused the greatest increase in proliferation (p<0.0001), and also caused significant increases in collagen(p<0.0001) and glycosaminoglycans (p<0.0001). DNA microarray data demonstrated upregulation of 5HTR2A and 5HTR2B (>4.5 fold) for cyclic-stretch versus static (p<0.001), while expression of the 5HT transporter was not changed significantly. Extracellular matrix genes (eg. Collagen Types I,II,III, and proteoglycans) were also upregulated by cyclic-stretch. Conclusions Porcine aortic valve cusp samples subjected to cyclic stretch upregulate 5HTR2A and 2B, and also initiate remodeling activity characterized by increased proliferation and collagen production. Importantly, enhanced 5HTR responsiveness, due to increased 5HTR2A and 2B expression, results in a significantly greater response in remodeling endpoints (proliferation, collagen and GAG production) to 5HT in the presence of 5HT transporter blockade. PMID:21718840

  6. Resveratrol Ameliorates High Glucose and High-Fat/Sucrose Diet-Induced Vascular Hyperpermeability Involving Cav-1/eNOS Regulation

    PubMed Central

    Peng, Xiao lin; Qu, Wei; Wang, Lin zhi; Huang, Bin qing; Ying, Chen jiang; Sun, Xiu fa; Hao, Li ping

    2014-01-01

    Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation. PMID:25419974

  7. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure.

    PubMed

    Winzer, Ephraim B; Gaida, Pauline; Höllriegel, Robert; Fischer, Tina; Linke, Axel; Schuler, Gerhard; Adams, Volker; Erbs, Sandra

    2016-01-01

    Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser(1177), dephosphorylation at Thr(495), and diminished phosphorylation of PKC-βII at Ser(660). The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function. PMID:27563480

  8. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

    PubMed Central

    Gaida, Pauline; Höllriegel, Robert; Fischer, Tina; Linke, Axel; Schuler, Gerhard; Adams, Volker; Erbs, Sandra

    2016-01-01

    Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function. PMID:27563480

  9. Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS

    PubMed Central

    Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung; Li, Rongsong

    2013-01-01

    Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter < 200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. PMID:23751346

  10. Increased aortic stiffness and related factors in patients with peripheral arterial disease.

    PubMed

    Catalano, Mariella; Scandale, Giovanni; Carzaniga, Gianni; Cinquini, Michela; Minola, Marzio; Dimitrov, Gabriel; Carotta, Maria

    2013-10-01

    A number of conditions have been associated with functional changes of large arteries. The aim of this study was to evaluate the factors associated with aortic stiffness in patients with peripheral arterial disease (PAD). The authors studied 86 patients with PAD (ankle-brachial pressure index [ABPI] ≤0.9) and 86 controls. Aortic stiffness was determined by pulse wave velocity (aPWV) using applanation tonometry. In PAD patients, aPWV was higher compared with controls (11 ± 3 vs 9.8 ± 1.8; P=.002). In multiple regression analysis, aPWV was independently associated with pulse pressure (β=0.05, P=.01) in the PAD patients and with age in the control group (β=0.08, P=.0005). The results of this study confirm an aPWV increase in patients with PAD and emphasize the association between blood pressure and aPWV. Further studies are necessary to assess whether higher aortic stiffening adds prognostic value to ABPI, which is the most powerful prognostic indicator in PAD. PMID:24088278

  11. Increased plant sterol deposition in vascular tissue characterizes patients with severe aortic stenosis and concomitant coronary artery disease.

    PubMed

    Luister, Alexandra; Schött, Hans Frieder; Husche, Constanze; Schäfers, Hans-Joachim; Böhm, Michael; Plat, Jogchum; Gräber, Stefan; Lütjohann, Dieter; Laufs, Ulrich; Weingärtner, Oliver

    2015-07-01

    The aim of the study was to evaluate the relationship between phytosterols, oxyphytosterols, and other markers of cholesterol metabolism and concomitant coronary artery disease (CAD) in patients with severe aortic stenosis who were scheduled for elective aortic valve replacement. Markers of cholesterol metabolism (plant sterols and cholestanol as markers of cholesterol absorption and lathosterol as an indicator of cholesterol synthesis) and oxyphytosterols were determined in plasma and aortic valve tissue from 104 consecutive patients with severe aortic stenosis (n=68 statin treatment; n=36 no statin treatment) using gas chromatography-flame ionization and mass spectrometry. The extent of CAD was determined by coronary angiography prior to aortic valve replacement. Patients treated with statins were characterized by lower plasma cholesterol, cholestanol, and lathosterol concentrations. However, statin treatment did not affect the sterol concentrations in cardiovascular tissue. The ratio of campesterol-to-cholesterol was increased by 0.46±0.34μg/mg (26.0%) in plasma of patients with CAD. The absolute values for the cholesterol absorption markers sitosterol and campesterol were increased by 18.18±11.59ng/mg (38.8%) and 11.40±8.69ng/mg (30.4%) in the tissues from patients with documented CAD compared to those without concomitant CAD. Campesterol oxides were increased by 0.06±0.02ng/mg (17.1%) in the aortic valve cusps and oxidized sitosterol-to-cholesterol ratios were up-regulated by 0.35±0.2ng/mg (22.7%) in the plasma of patients with CAD. Of note, neither cholestanol nor the ratio of cholestanol-to-cholesterol was associated with CAD. Patients with concomitant CAD are characterized by increased deposition of plant sterols, but not cholestanol in aortic valve tissue. Moreover, patients with concomitant CAD were characterized by increased oxyphytosterol concentrations in plasma and aortic valve cusps.

  12. Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

    PubMed

    Raijmakers, P G; Groeneveld, A B; Rauwerda, J A; Schneider, A J; Teule, G J; Hack, C E; Thijs, L G

    1995-03-01

    Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Ionizing radiation increases adhesiveness of human aortic endothelial cells via a chemokine-dependent mechanism.

    PubMed

    Khaled, Saman; Gupta, Kiran B; Kucik, Dennis F

    2012-05-01

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved.

  14. Changes in wall shear stresses in abdominal aortic aneurysms with increasing wall stiffness

    NASA Astrophysics Data System (ADS)

    Salsac, Anne-Virginie; Fernandez, Miguel

    2006-11-01

    During the growth of abdominal aortic aneurysms, local changes occur in the composition and structure of the diseased wall, resulting in its stiffening. A numerical simulation of the fluid structure interactions is performed in idealized models of aneurysms using a finite element method. A full coupling of the equations governing the pulsatile blood flow and the deformation of the compliant wall is undertaken. The effect of the progressive stiffening of the wall is analyzed at various stages in the growth of the aneurysm. Increasing the wall stiffness alters the distribution of wall shear stresses and leads to an increase in their magnitude. The wall compliance is shown to have a more pronounced effect on non-axisymmetric aneurysms, which sustain large displacements. The overall movement of the aneurysm models increases the three-dimensionality of the flow.

  15. 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

  16. Side-Specific Endothelial-Dependent Regulation of Aortic Valve Calcification

    PubMed Central

    Richards, Jennifer; El-Hamamsy, Ismail; Chen, Si; Sarang, Zubair; Sarathchandra, Padmini; Yacoub, Magdi H.; Chester, Adrian H.; Butcher, Jonathan T.

    2014-01-01

    Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker l-NAME augmented calcification even in 3D VIC–VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and α-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology. PMID:23499458

  17. Acute Aortic Syndromes and Thoracic Aortic Aneurysm

    PubMed Central

    Ramanath, Vijay S.; Oh, Jae K.; Sundt, Thoralf M.; Eagle, Kim A.

    2009-01-01

    Acute and chronic aortic diseases have been diagnosed and studied by physicians for centuries. Both the diagnosis and treatment of aortic diseases have been steadily improving over time, largely because of increased physician awareness and improvements in diagnostic modalities. This comprehensive review discusses the pathophysiology and risk factors, classification schemes, epidemiology, clinical presentations, diagnostic modalities, management options, and outcomes of various aortic conditions, including acute aortic dissection (and its variants intramural hematoma and penetrating aortic ulcers) and thoracic aortic aneurysms. Literature searches of the PubMed database were conducted using the following keywords: aortic dissection, intramural hematoma, aortic ulcer, and thoracic aortic aneurysm. Retrospective and prospective studies performed within the past 20 years were included in the review; however, most data are from the past 15 years. PMID:19411444

  18. 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

  19. eNOS Genetic Polymorphisms and Cancer Risk

    PubMed Central

    Gao, Xueren; Wang, Jie; Wang, Wenjun; Wang, Mingxi; Zhang, Jianqiong

    2015-01-01

    Abstract The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case–control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case–control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV. In conclusion, our meta-analysis and case–control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer. PMID:26131841

  20. Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction

    PubMed Central

    Torrado, Juan; Farro, Ignacio; Zócalo, Yanina; Farro, Federico; Sosa, Claudio; Scasso, Santiago; Alonso, Justo; Bia, Daniel

    2015-01-01

    Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about “recruitability” of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with “basal and recruitable” EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both “resting and recruitable” endothelial dysfunctions. PMID:26351578

  1. Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction.

    PubMed

    Torrado, Juan; Farro, Ignacio; Zócalo, Yanina; Farro, Federico; Sosa, Claudio; Scasso, Santiago; Alonso, Justo; Bia, Daniel

    2015-01-01

    Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about "recruitability" of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with "basal and recruitable" EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both "resting and recruitable" endothelial dysfunctions.

  2. Vascular calcification is not associated with increased ambulatory central aortic systolic pressure in prevalent dialysis patients

    PubMed Central

    Freercks, Robert J; Swanepoel, Charles R; Turest-Swartz, Kristy L; Rayner, Brian L; Carrara, Henri RO; Moosa, Sulaiman EI; Lachman, Anthony S

    2014-01-01

    Summary Introduction Central aortic systolic pressure (CASP) strongly predicts cardiovascular outcomes. We undertook to measure ambulatory CASP in 74 prevalent dialysis patients using the BPro (HealthStats, Singapore) device. We also determined whether coronary or abdominal aortic calcification was associated with changes in CASP and whether interdialytic CASP predicted ambulatory measurement. Methods All patients underwent computed tomography for coronary calcium score, lateral abdominal radiography for aortic calcium score, echocardiography for left ventricular mass index and ambulatory blood pressure measurement using BPro calibrated to brachial blood pressure. HealthStats was able to convert standard BPro SOFT® data into ambulatory CASP. Results Ambulatory CASP was not different in those without and with coronary (137.6 vs 141.8 mmHg, respectively, p = 0.6) or aortic (136.6 vs 145.6 mmHg, respectively, p = 0.2) calcification. Furthermore, when expressed as a percentage of brachial systolic blood pressure to control for peripheral blood pressure, any difference in CASP was abolished: CASP: brachial systolic blood pressure ratio = 0.9 across all categories regardless of the presence of coronary or aortic calcification (p = 0.2 and 0.4, respectively). Supporting this finding, left ventricular mass index was also not different in those with or without vascular calcification (p = 0.7 and 0.8 for coronary and aortic calcification). Inter-dialytic office blood pressure and CASP correlated excellently with ambulatory measurements (r = 0.9 for both). Conclusion Vascular calcification was not associated with changes in ambulatory central aortic systolic pressure in this cohort of prevalent dialysis patients. Inter-dialytic blood pressure and CASP correlated very well with ambulatory measurement. PMID:24626513

  3. Are Aortic Stent Grafts Safe in Pregnancy?

    PubMed Central

    Khandanpour, Nader; Mehta, Tapan A.; Adiseshiah, M.; Meyer, Felicity J.

    2015-01-01

    Aortic stent grafts are increasingly used to treat aortic aneurysms and also other aortic pathologies. The safety of aortic stent grafts in pregnancy has never been studied or reported. We report on two cases of aortic stent grafts in pregnant women and discuss the effect of pregnancy on these aortic stent grafts. PMID:26229702

  4. Wave reflection and central aortic pressure are increased in response to static and dynamic muscle contraction at comparable workloads.

    PubMed

    Edwards, David G; Mastin, Corey R; Kenefick, Robert W

    2008-02-01

    We determined the effects of static and dynamic muscle contraction at equivalent workloads on central aortic pressure and wave reflection. At random, 14 healthy men and women (23 +/- 5 yr of age) performed a static handgrip forearm contraction [90 s at 30% of maximal voluntary contraction (MVC)], dynamic handgrip contractions (1 contraction/s for 180 s at 30% MVC), and a control trial. During static and dynamic trials, tension-time index was controlled by holding peak tension constant. Measurements of brachial artery blood pressure and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were conducted at baseline, during each trial, and during 1 min of postexercise ischemia (PEI). Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. AI increased during both static and dynamic trials (static, 5.2 +/- 3.1 to 11.8 +/- 3.4%; dynamic, 5.8 +/- 3.0 to 13.3 +/- 3.4%; P < 0.05) and further increased during PEI (static, 18.5 +/- 3.1%; dynamic, 18.6 +/- 2.9%; P < 0.05). Peripheral and central systolic and diastolic pressures increased (P < 0.05) during both static and dynamic trials and remained elevated during PEI. AI and pressure responses did not differ between static and dynamic trials. Peripheral and central pressures increased similarly during static and dynamic contraction; however, the rise in central systolic pressure during both conditions was augmented by increased wave reflection. The present data suggest that wave reflection is an important determinant of the central blood pressure response during forearm muscle contractions.

  5. Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study.

    PubMed

    McCloskey, Kate; Burgner, David; Carlin, John B; Skilton, Michael R; Cheung, Michael; Dwyer, Terence; Vuillermin, Peter; Ponsonby, Anne-Louise

    2016-03-01

    Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6; P<0.001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5; P<0.001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3; P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.

  6. Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study.

    PubMed

    McCloskey, Kate; Burgner, David; Carlin, John B; Skilton, Michael R; Cheung, Michael; Dwyer, Terence; Vuillermin, Peter; Ponsonby, Anne-Louise

    2016-03-01

    Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6; P<0.001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5; P<0.001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3; P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk. PMID:26666445

  7. A Maillard reaction product enhances eNOS activity in human endothelial cells.

    PubMed

    Schmitt, Christoph A; Heiss, Elke H; Schachner, Daniel; Aristei, Yasmin; Severin, Theodor; Dirsch, Verena M

    2010-07-01

    Nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS) is an important signaling molecule in the cardiovascular system. Although dietary factors can modulate eNOS activity, putative effects of processed food are barely investigated. We aimed to examine whether the model Maillard reaction product 3-hydroxy-2-methyl-1-propyl-4(1H)-pyridone (HMPP), formed from maltol or starch and propylamine, affects the eNOS system. Incubation of EA.hy926 endothelial cells with 30-300 microM HMPP for 18 h enhanced endothelial NO release measured with the fluorescent probe diaminofluorescein-2 and eNOS activity determined by the [14C]L-arginine-[14C]L-citrulline conversion assay. HMPP increased NO production also in two different types of primary human endothelial cells. Protein levels of eNOS and inducible NO synthase remained unaltered by HMPP. HMPP inhibited eNOS activity within the first 2-4 h, whereas it potently increased eNOS activity after 12-24 h. Levels of eNOS phosphorylation, expression of heat-shock protein 90, caveolin-1 and various antioxidant enzymes were not affected. Intracellular reactive oxygen species remained unchanged by HMPP. This is the first study to demonstrate positive effects of a Maillard reaction product on eNOS activity and endothelial NO production, which is considered favourable for cardiovascular protection. PMID:20112298

  8. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    PubMed

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  9. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    PubMed

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells. PMID:26977592

  10. Activation of protease calpain by oxidized and glycated LDL increases the degradation of endothelial nitric oxide synthase

    PubMed Central

    Dong, Yunzhou; Wu, Yong; Wu, Mingyuan; Wang, Shuangxi; Zhang, Junhua; Xie, Zhonglin; Xu, Jian; Song, Ping; Wilson, Kenneth; Zhao, Zhengxing; Lyons, Timothy; Zou, Ming-Hui

    2009-01-01

    Oxidation and glycation of low-density lipoprotein (LDL) promote vascular injury in diabetes; however, the mechanisms underlying this effect remain poorly defined. The present study was conducted to determine the effects of ‘heavily oxidized’ glycated LDL (HOG-LDL) on endothelial nitric oxide synthase (eNOS) function. Exposure of bovine aortic endothelial cells with HOG-LDL reduced eNOS protein levels in a concentration- and time-dependent manner, without altering eNOS mRNA levels. Reduced eNOS protein levels were accompanied by an increase in intracellular Ca2+, augmented production of reactive oxygen species (ROS) and induction of Ca2+-dependent calpain activity. Neither eNOS reduction nor any of these other effects were observed in cells exposed to native LDL. Reduction of intracellular Ca2+ levels abolished eNOS reduction by HOG-LDL, as did pharmacological or genetic through calcium channel blockers or calcium chelator BAPTA or inhibition of NAD(P)H oxidase (with apocynin) or inhibition of calpain (calpain 1-specific siRNA). Consistent with these results, HOG-LDL impaired acetylcholine-induced endothelium-dependent vasorelaxation of isolated mouse aortas, and pharmacological inhibition of calpain prevented this effect. HOG-LDL may impair endothelial function by inducing calpain-mediated eNOS degradation in a ROS- and Ca2+-dependent manner. PMID:18624772

  11. Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness.

    PubMed

    Nguy, Lisa; Johansson, Maria E; Grimberg, Elisabeth; Lundgren, Jaana; Teerlink, Tom; Carlström, Mattias; Lundberg, Jon O; Nilsson, Holger; Guron, Gregor

    2013-05-01

    Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 ± 10 and 119 ± 9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 ± 6 mmHg in A-CRF animals vs. 2 ± 1 mmHg in controls (P < 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12 ± 3 vs. -5 ± 5 mmHg, P < 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 ± 0.51 vs. 4.58 ± 0.17 m/s, P < 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 ± 46 vs. 31 ± 2 μM, P < 0.001), whereas plasma renin activity was suppressed (0.6 ± 0.5 vs. 12.3 ± 7.3 μg·l(-1)·h(-1), P < 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity.

  12. Weather conditions and their effect on the increase of the risk of type A acute aortic dissection onset in Berlin

    NASA Astrophysics Data System (ADS)

    Taheri Shahraiyni, Hamid; Sodoudi, Sahar; Cubasch, Ulrich

    2016-08-01

    In this study, a minimum distance classification and forward feature selection technique are joined to determine the relationship between weather conditions and the increase of the risk of type A acute aortic dissection (AAD) events in Berlin. The results demonstrate that changes in the amount of cloudiness and air temperature are the most representative weather predictors among the studied parameters. A discrimination surface was developed for the prediction of AAD events 6 h ahead, and it is found that, under a specific amount of cloudiness and air temperature, the risk of AAD events in Berlin increases about 20 %.

  13. Molecular characterisation and expression profiling of the ENO1 gene in the ovarian follicle of the Sichuan white goose.

    PubMed

    Kang, Bo; Jiang, Dong Mei; Bai, Lin; He, Hui; Ma, Rong

    2014-01-01

    The ENO1 gene encodes a multifunctional enzyme that has been identified as a key component of the glycolytic pathway. Our previous studies demonstrated that ENO1 gene expression was higher in the ovaries of laying geese compared with prelaying geese. However, the molecular characterisation and expression profiling of the ENO1 gene in geese tissues and ovarian follicles remain to be determined. In this study, ENO1 cDNA (1,445 bp long) of the Sichuan white goose was cloned and characterised. The ORF of ENO1 cDNA is 1,305 bp in length and encodes a 434 amino acid protein with a molecular weight of 47.27 kDa. ENO1 expression in all of the examined tissues was the highest in spleen and the lowest in breast muscle. High expression of ENO1 appeared in the kidney, liver, adrenal gland, and retina. With increasing follicle growth, ENO1 gene expression began to decrease from the small white follicle to F5, which was followed by a sharp increase in expression in F4 and then a gradual decrease in expression from F3 to F1. Furthermore, in the postovulatory follicles (POF), the levels of ENO1 gene expression decreased gradually from POF1 to POF4. In conclusion, the ENO1 transcript was widely distributed in various tissues of the Sichuan white goose, but ENO1 expression was tissue-specific. Furthermore, the results of the ENO1 expression profiling of ovarian follicles suggest that ENO1 may play an important dual role in the progress of follicular development, where ENO1 acts as a glycolytic enzyme and also mediates apoptosis.

  14. [Aortic aneurysm].

    PubMed

    Villar, Fernando; Pedro-Botet, Juan; Vila, Ramón; Lahoz, Carlos

    2013-01-01

    Aortic aneurysm is one important cause of death in our country. The prevalence of abdominal aortic aneurism (AAA) is around 5% for men older than 50 years of age. Some factors are associated with increased risk for AAA: age, hypertension, hypercholesterolemia, cardiovascular disease and, in particular, smoking. The medical management of patients with an AAA includes cardiovascular risk treatment, particularly smoking cessation. Most of major societies guidelines recommend ultrasonography screening for AAA in men aged 65 to 75 years who have ever smoked because it leads to decreased AAA-specific mortality. PMID:24238836

  15. Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production

    PubMed Central

    2014-01-01

    Background It has been reported that GLP-1 agonist exenatide (exendin-4) decreases blood pressure. The dose-dependent vasodilator effect of exendin-4 has previously been demonstrated, although the precise mechanism is not thoroughly described. Here we have aimed to provide in vitro evidence for the hypothesis that exenatide may decrease central (aortic) blood pressure involving three gasotransmitters, namely nitric oxide (NO) carbon monoxide (CO), and hydrogen sulphide (H2S). Methods We determined the vasoactive effect of exenatide on isolated thoracic aortic rings of adult rats. Two millimetre-long vessel segments were placed in a wire myograph and preincubated with inhibitors of the enzymes producing the three gasotransmitters, with inhibitors of reactive oxygen species formation, prostaglandin synthesis, inhibitors of protein kinases, potassium channels or with an inhibitor of the Na+/Ca2+-exchanger. Results Exenatide caused dose-dependent relaxation of rat thoracic aorta, which was evoked via the GLP-1 receptor and was mediated mainly by H2S but also by NO and CO. Prostaglandins and superoxide free radical also play a part in the relaxation. Inhibition of soluble guanylyl cyclase significantly diminished vasorelaxation. We found that ATP-sensitive-, voltage-gated- and calcium-activated large-conductance potassium channels are also involved in the vasodilation, but that seemingly the inhibition of the KCNQ-type voltage-gated potassium channels resulted in the most remarkable decrease in the rate of vasorelaxation. Inhibition of the Na+/Ca2+-exchanger abolished most of the vasodilation. Conclusions Exenatide induces vasodilation in rat thoracic aorta with the contribution of all three gasotransmitters. We provide in vitro evidence for the potential ability of exenatide to lower central (aortic) blood pressure, which could have relevant clinical importance. PMID:24693878

  16. Conservative Management of Chronic Aortic Dissection with Underlying Aortic Aneurysm

    PubMed Central

    Yusuf Beebeejaun, Mohammad; Malec, Aleksandra; Gupta, Ravi

    2013-01-01

    Aortic dissection is one of the most common aortic emergencies affecting around 2000 Americans each year. It usually presents in the acute state but in a small percentage of patients aortic dissections go unnoticed and these patients survive without any adequate therapy. With recent advances in medical care and diagnostic technologies, aortic dissection can be successfully managed through surgical or medical options, consequently increasing the related survival rate. However, little is known about the optimal long-term management of patients suffering from chronic aortic dissection. The purpose of the present report is to review aortic dissection, namely its pathology and the current diagnostic tools available, and to discuss the management options for chronic aortic dissection. We report a patient in which chronic aortic dissection presented with recurring episodes of vomiting and also discuss the management plan of our patient who had a chronic aortic dissection as well as an underlying aortic aneurysm. PMID:24179638

  17. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol.

    PubMed

    Xia, Ning; Strand, Susanne; Schlufter, Frank; Siuda, Daniel; Reifenberg, Gisela; Kleinert, Hartmut; Förstermann, Ulrich; Li, Huige

    2013-08-01

    Many of the cardiovascular protective effects of resveratrol are attributable to an enhanced production of nitric oxide (NO) by the endothelial NO synthase (eNOS). Resveratrol has been shown to enhance eNOS gene expression as well as eNOS enzymatic activity. The aim of the present study was to analyze the molecular mechanisms of eNOS transcriptional activation by resveratrol. Treatment of human EA.hy 926 endothelial cells with resveratrol led to a concentration-dependent upregulation of eNOS expression. In luciferase reporter gene assay, resveratrol enhanced the activity of human eNOS promoter fragments (3500, 1600, 633 and 263bp in length, respectively), indicating that the proximal promoter region is required for resveratrol-induced eNOS transcriptional activation. Knockdown of the NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1) by siRNA prevented the upregulation of eNOS mRNA and protein by resveratrol. Forkhead box O (FOXO) transcription factors are established downstream targets of SIRT1. siRNA-mediated knockdown of FOXO1 and FOXO3a abolished the effect of resveratrol on eNOS expression, indicating the involvement of these factors. Resveratrol treatment enhanced the expression of FOXO1 and FOXO3a in EA.hy 926 cells. Reporter gene assay using promoter containing forkhead response elements showed increased FOXO factor activity by resveratrol. In electrophoretic mobility shift assay, the enhanced binding of nuclear proteins to the eNOS promoter regions by resveratrol could be blocked by antibodies against FOXO1 and FOXO3a. In conclusion, resveratrol enhances the expression and activity of FOXO transcription factors. The SIRT1/FOXO factor axis is involved in resveratrol-induced eNOS transcriptional activation.

  18. 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

  19. Low Relative Lean Mass is Associated with Increased Likelihood of Abdominal Aortic Calcification in Community-Dwelling Older Australians.

    PubMed

    Rodríguez, Alexander J; Scott, David; Khan, Belal; Khan, Nayab; Hodge, Allison; English, Dallas R; Giles, Graham G; Ebeling, Peter R

    2016-10-01

    Age-related loss of skeletal muscle is associated with increased risk of functional limitation and cardiovascular (CV) mortality. In the elderly abdominal aortic calcification (AAC) can increase CV risk by altering aortic properties which may raise blood pressure and increase cardiac workload. This study investigated the association between low muscle mass and AAC in community-dwelling older Australians. Data for this cross-sectional analysis were drawn from a 2010 sub-study of the Melbourne Collaborative Cohort Study in the setting of community-dwelling older adults. Three hundred and twenty-seven participants [mean age = 71 ± 6 years; mean BMI = 28 ± 5 kg/m(2); females n = 199 (62 %)] had body composition determined by dual-energy x-ray absorptiometry (DXA) and AAC determined by radiography. Participants were stratified into tertiles of sex-specific BMI-normalised appendicular lean mass (ALM). Those in the lowest tertile were considered to have low relative muscle mass. Aortic calcification score (ACS) was determined visually as the extent of calcification on the aortic walls between L1 and L4 vertebrae (range: 0-24). Severe AAC was defined as ACS ≥ 6. Prevalence of any AAC was highest in participants with low relative muscle mass (74 %) compared to the middle (65 %) and upper (53 %) tertiles (p trend = 0.006). The lower ALM/BMI tertile had increased odds (Odds ratio = 2.3; 95 % confidence interval: 1.1-4.6; p = 0.021) of having any AAC; and having more severe AAC (2.2; 1.2-4.0; p = 0.009) independent of CV risk factors, serum calcium and physical activity. AAC is more prevalent and severe in community-dwelling older adults with low relative muscle mass. Maintaining muscle mass could form part of a broader primary prevention strategy in reducing AAC. PMID:27272030

  20. Fibulin-4 deficiency increases TGF-β signalling in aortic smooth muscle cells due to elevated TGF-β2 levels.

    PubMed

    Ramnath, N W M; Hawinkels, L J A C; van Heijningen, P M; te Riet, L; Paauwe, M; Vermeij, M; Danser, A H J; Kanaar, R; ten Dijke, P; Essers, J

    2015-11-26

    Fibulins are extracellular matrix proteins associated with elastic fibres. Homozygous Fibulin-4 mutations lead to life-threatening abnormalities such as aortic aneurysms. Aortic aneurysms in Fibulin-4 mutant mice were associated with upregulation of TGF-β signalling. How Fibulin-4 deficiency leads to deregulation of the TGF-β pathway is largely unknown. Isolated aortic smooth muscle cells (SMCs) from Fibulin-4 deficient mice showed reduced growth, which could be reversed by treatment with TGF-β neutralizing antibodies. In Fibulin-4 deficient SMCs increased TGF-β signalling was detected using a transcriptional reporter assay and by increased SMAD2 phosphorylation. Next, we investigated if the increased activity was due to increased levels of the three TGF-β isoforms. These data revealed slightly increased TGF-β1 and markedly increased TGF-β2 levels. Significantly increased TGF-β2 levels were also detectable in plasma from homozygous Fibulin-4(R/R) mice, not in wild type mice. TGF-β2 levels were reduced after losartan treatment, an angiotensin-II type-1 receptor blocker, known to prevent aortic aneurysm formation. In conclusion, we have shown increased TGF-β signalling in isolated SMCs from Fibulin-4 deficient mouse aortas, not only caused by increased levels of TGF-β1, but especially TGF-β2. These data provide new insights in the molecular interaction between Fibulin-4 and TGF-β pathway regulation in the pathogenesis of aortic aneurysms.

  1. Fibulin-4 deficiency increases TGF-β signalling in aortic smooth muscle cells due to elevated TGF-β2 levels

    PubMed Central

    Ramnath, N. W. M.; Hawinkels, L. J. A. C.; van Heijningen, P. M.; Riet, L. te; Paauwe, M.; Vermeij, M.; Danser, A. H. J.; Kanaar, R.; ten Dijke, P.; Essers, J.

    2015-01-01

    Fibulins are extracellular matrix proteins associated with elastic fibres. Homozygous Fibulin-4 mutations lead to life-threatening abnormalities such as aortic aneurysms. Aortic aneurysms in Fibulin-4 mutant mice were associated with upregulation of TGF-β signalling. How Fibulin-4 deficiency leads to deregulation of the TGF-β pathway is largely unknown. Isolated aortic smooth muscle cells (SMCs) from Fibulin-4 deficient mice showed reduced growth, which could be reversed by treatment with TGF-β neutralizing antibodies. In Fibulin-4 deficient SMCs increased TGF-β signalling was detected using a transcriptional reporter assay and by increased SMAD2 phosphorylation. Next, we investigated if the increased activity was due to increased levels of the three TGF-β isoforms. These data revealed slightly increased TGF-β1 and markedly increased TGF-β2 levels. Significantly increased TGF-β2 levels were also detectable in plasma from homozygous Fibulin-4R/R mice, not in wild type mice. TGF-β2 levels were reduced after losartan treatment, an angiotensin-II type-1 receptor blocker, known to prevent aortic aneurysm formation. In conclusion, we have shown increased TGF-β signalling in isolated SMCs from Fibulin-4 deficient mouse aortas, not only caused by increased levels of TGF-β1, but especially TGF-β2. These data provide new insights in the molecular interaction between Fibulin-4 and TGF-β pathway regulation in the pathogenesis of aortic aneurysms. PMID:26607280

  2. Attenuation of signaling and nitric oxide production following prolonged leptin exposure in human aortic endothelial cells.

    PubMed

    Blanquicett, Carmelo; Graves, Anitra; Kleinhenz, Dean J; Hart, C Michael

    2007-11-01

    Acute leptin exposure stimulates endothelial nitric oxide (NO) production in vitro. In contrast, chronic elevations in circulating leptin levels in patients with obesity are associated with endothelial dysfunction and impaired endothelial NO production. Therefore, the goal of the current study was to examine the direct effects of acute and more sustained leptin stimulation on endothelial nitric oxide synthase (eNOS) and NO production in human aortic endothelial cells (HAECs). HAECs were treated with vehicle or with leptin (5 or 60 ng/mL) acutely (30-60 minutes) or for 72 hours. HAEC NO release into culture media was measured with a chemiluminescence technique, and superoxide (O(2)(-.)) production was measured with electron spin resonance (ESR) spectroscopy. HAEC eNOS activity was measured as the conversion of (3)H-arginine to (3)H-citrulline, and protein levels of eNOS, phospho-eNOS (serine 1177), Erk, phospho-Erk, suppressor of cytokine signaling (SOCS3), xanthine oxidase (XO), and the reduced nicotinamide adenine dinucleotide (NADPH) oxidase components p22phox, p67phox, Nox-4, and gp91phox were examined by Western blotting or immunoprecipitation. Acute leptin exposure increased eNOS serine 1177 phosphorylation and caused Erk activation. In contrast, prolonged leptin stimulation was not cytotoxic and failed to alter eNOS expression, phosphorylation, or HAEC NO release. Furthermore, prolonged leptin stimulation did not alter O(2)(-.) production or NADPH oxidase or XO expression but increased SOCS3 expression. In contrast to acute stimulation, prolonged (72 hours) stimulation does not alter endothelial cell NO or O(2)(-.) production. We postulate that chronic leptin stimulation, through increased SOCS3 expression, may attenuate the effects of leptin on vascular endothelial function. PMID:18062898

  3. 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. PMID:26286023

  4. 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

  5. Endothelin stimulates a sustained 1,2-diacylglycerol increase and protein kinase C activation in bovine aortic smooth muscle cells

    SciTech Connect

    Lee, T.S.; Chao, T.; Hu, K.Q.; King, G.L.

    1989-07-14

    Endothelin is a long-lasting potent vasoconstrictor peptide. We report here that in bovine aortic smooth muscle cells, endothelin biphasically increased total cellular diacylglycerol (DAG) content. When cellular DAG was labeled with (/sup 14/C) glycerol for 48h, endothelin stimulated (/sup 14/C)DAG formation in a biphasic pattern. Only one prolonged phase of DAG accumulation was observed when cells were labeled with (/sup 3/H)glycerol for 2 h. Endothelin induced an increase in the membranous protein kinase C (PKC) activities, which lasted for more than 20 min. These data suggest that (i) endothelin stimulates a sustained generation of DAG, (ii) this accumulation of DAG results in a sustained translocation of cytosolic PKC activities to the membrane.

  6. Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest

    PubMed Central

    Riganti, Chiara; Chattaragada, Michelle Samuel; Principe, Moitza; Roux, Cecilia; Zhou, Weidong; Petricoin, Emanuel F.; Cappello, Paola; Novelli, Francesco

    2016-01-01

    In the last 5 years, novel knowledge on tumor metabolism has been revealed with the identification of critical factors that fuel tumors. Alpha-enolase (ENO1) is commonly over-expressed in tumors and is a clinically relevant candidate molecular target for immunotherapy. Here, we silenced ENO1 in human cancer cell lines and evaluated its impact through proteomic, biochemical and functional approaches. ENO1 silencing increased reactive oxygen species that were mainly generated through the sorbitol and NADPH oxidase pathways, as well as autophagy and catabolic pathway adaptations, which together affect cancer cell growth and induce senescence. These findings represent the first comprehensive metabolic analysis following ENO1 silencing. Inhibition of ENO1, either alone, or in combination with other pathways which were perturbed by ENO1 silencing, opens novel avenues for future therapeutic approaches. PMID:26734996

  7. Serum Carboxymethyl-lysine, an Advanced Glycation End Product, is Associated with Increased Aortic Pulse Wave Velocity in Adults

    PubMed Central

    Semba, Richard D.; Najjar, Samer S.; Sun, Kai; Lakatta, Edward G.; Ferrucci, Luigi

    2008-01-01

    Background The relationship between advanced glycation end products and arterial stiffness has previously been examined in highly selected groups of patients with diabetes or hypertension. Our aim was to determine whether elevated serum advanced glycation end products are associated with increased arterial stiffness in relatively healthy, community-dwelling adults. Methods Aortic pulse wave velocity (PWV), an index of aortic stiffness, and serum AGEs, as represented by the specific AGE, serum carboxymethyl-lysine (CML), were measured in 493 adults, aged 26-93 years, who participated in the Baltimore Longitudinal Study of Aging. Results Mean (SD) PWV (m/sec) was 6.6 (1.8) m/sec. Mean CML was 0.47 (0.13) μg/mL. Serum CML (per 1 Standard Deviation [S.D.]) was associated with PWV (beta = 0.16, standard error [S.E.] = 0.07, P = 0.02), adjusting for age, sex, body mass index, mean arterial pressure, fasting plasma glucose, high density lipoprotein cholesterol, smoking, and other covariates. After excluding all diabetic patients, serum CML (per 1 S.D.) was associated with PWV (beta = 0.18, S.E. = 0.07, P = 0.009), adjusting for the same covariates. Conclusions Elevated AGEs are associated with increased arterial stiffness, a known predictor of adverse cardiovascular outcomes, among relatively healthy community-dwelling adults. Interventions to lower levels of AGEs, such as altering the pattern of dietary intake, warrant examination as putative novel strategies to lower arterial stiffness in adults. PMID:19023277

  8. Prunella vulgaris L. Upregulates eNOS expression in human endothelial cells.

    PubMed

    Xia, Ning; Bollinger, Larissa; Steinkamp-Fenske, Katja; Förstermann, Ulrich; Li, Huige

    2010-01-01

    The purported effects of "circulation-improving" herbs used in traditional Chinese medicine (TCM) show striking similarities with the vascular actions of nitric oxide (NO) produced by the endothelial NO synthase (eNOS). We have previously reported that Salviae miltiorrhizae radix and Zizyphi spinosae semen upregulate eNOS expression. In the present study, we studied the effect on eNOS gene expression of 15 Chinese herbs with potential effects on the vasculature, and identified Prunella vulgaris L. (PVL) (flowering spike) as a potent eNOS-upregulating agent. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVEC), an aqueous extract of PVL increased eNOS promoter activity, eNOS mRNA and protein expressions, as well as NO production in concentration- and time-dependent manners. We have previously shown that ursolic acid (a constituent of Salviae miltiorrhizae radix), betulinic acid (a compound present in Zizyphi spinosae semen), luteolin and cynaroside (ingredients of artichoke, Cynara scolymus L.) are capable of enhancing eNOS gene expression. These compounds are also present in significant quantities in PVL. Thus, PVL contains active principles that stimulate human eNOS gene expression, and such compounds may have therapeutic potential against cardiovascular diseases. PMID:20503475

  9. Reoperative transapical transcatheter aortic valve replacement for central aortic regurgitation.

    PubMed

    Zhu, Yuanjia; Kapadia, Samir; Krishnaswamy, Amar; Svensson, Lars G; Mick, Stephanie

    2016-09-01

    Paravalvular leak-related aortic regurgitation after transcatheter aortic valve replacement (TAVR) is a common complication and is associated with increased short- and long-term mortality. However, the impact of isolated central aortic regurgitation is unknown. We report a case of transapical (TA) TAVR with postprocedural central aortic regurgitation, who returned after two years with progression of regurgitation. A reoperative valve-in-valve TA-TAVR was performed. PMID:27405799

  10. A comparison of ENO and TVD schemes

    NASA Technical Reports Server (NTRS)

    Chang, Shih-Hung; Liou, Meng-Sing

    1988-01-01

    The numerical performance of a second-order upwind-based TVD scheme is compared with that of a uniform second-order ENO scheme on shock capturing. The cases considered include flows with Mach numbers of 2.9, 5.0, and 10.0. For cases with Mach numbers of 5.0 and 10.0, the computed ENO results are inferior to the corresponding TVD results.

  11. Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A–dependent eNOS inactivation

    PubMed Central

    García, Celina; Aranda, Jorge; Arnold, Edith; Thébault, Stéphanie; Macotela, Yazmín; López-Casillas, Fernando; Mendoza, Valentín; Quiroz-Mercado, Hugo; Hernández-Montiel, Hebert Luis; Lin, Sue-Hwa; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2008-01-01

    Increased retinal vasopermeability contributes to diabetic retinopathy, the leading cause of blindness in working-age adults. Despite clinical progress, effective therapy remains a major need. Vasoinhibins, a family of peptides derived from the protein hormone prolactin (and inclusive of the 16-kDa fragment of prolactin), antagonize the proangiogenic effects of VEGF, a primary mediator of retinal vasopermeability. Here, we demonstrate what we believe to be a novel function of vasoinhibins as inhibitors of the increased retinal vasopermeability associated with diabetic retinopathy. Vasoinhibins inhibited VEGF-induced vasopermeability in bovine aortic and rat retinal capillary endothelial cells in vitro. In vivo, vasoinhibins blocked retinal vasopermeability in diabetic rats and in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy. Inhibition by vasoinhibins was similar to that achieved following immunodepletion of VEGF from human diabetic retinopathy vitreous or blockage of NO synthesis, suggesting that vasoinhibins inhibit VEGF-induced NOS activation. We further showed that vasoinhibins activate protein phosphatase 2A (PP2A), leading to eNOS dephosphorylation at Ser1179 and, thereby, eNOS inactivation. Moreover, intravitreous injection of okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on endothelial cell permeability and retinal vasopermeability. These results suggest that vasoinhibins have the potential to be developed as new therapeutic agents to control the excessive retinal vasopermeability observed in diabetic retinopathy and other vasoproliferative retinopathies. PMID:18497878

  12. eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom.

    PubMed

    Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; da Cruz-Höfling, Maria Alice

    2015-09-15

    Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed-spider causes excitotoxic signals and blood-brain barrier breakdown (BBBb) in rats. Nitric oxide (NO) is a signaling molecule which has a role in endothelium homeostasis and vascular health. The present study investigated the relevance of endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution induced by PNV. eNOS immunoblotting of cerebellum lysates processed through low-temperature SDS-PAGE revealed significant increased monomerization of the enzyme at critical periods of severe envenoming (1-2 h), whereas eNOS dimerization reversal paralleled to amelioration of animals condition (5-72 h). Moreover, eNOS uncoupling was accompanied by increased expression in calcium-sensing calmodulin protein and calcium-binding calbindin-D28 protein in cerebellar neurons. It is known that greater eNOS monomers than dimers implies the inability of eNOS to produce NO leading to superoxide production and endothelial/vascular barrier dysfunction. We suggest that transient eNOS deactivation and disturbances in calcium handling reduce NO production and enhance production of free radicals thus contributing to endothelial dysfunction in the cerebellum of envenomed rats. In addition, eNOS uncoupling compromises the enzyme capacity to respond to shear stress contributing to perivascular edema and it is one of the mechanisms involved in the BBBb promoted by PNV.

  13. Glutathionylation Mediates Angiotensin II–Induced eNOS Uncoupling, Amplifying NADPH Oxidase‐Dependent Endothelial Dysfunction

    PubMed Central

    Galougahi, Keyvan Karimi; Liu, Chia‐Chi; Gentile, Carmine; Kok, Cindy; Nunez, Andrea; Garcia, Alvaro; Fry, Natasha A. S.; Davies, Michael J.; Hawkins, Clare L.; Rasmussen, Helge H.; Figtree, Gemma A.

    2014-01-01

    Background Glutathionylation of endothelial nitric oxide synthase (eNOS) “uncouples” the enzyme, switching its function from nitric oxide (NO) to O2•− generation. We examined whether this reversible redox modification plays a role in angiotensin II (Ang II)‐induced endothelial dysfunction. Methods and Results Ang II increased eNOS glutathionylation in cultured human umbilical vein endothelial cells (HUVECs), rabbit aorta, and human arteries in vitro. This was associated with decreased NO bioavailability and eNOS activity as well as increased O2•− generation. Ang II‐induced decrease in eNOS activity was mediated by glutathionylation, as shown by restoration of function by glutaredoxin‐1. Moreover, Ang II‐induced increase in O2•− and decrease in NO were abolished in HUVECs transiently transfected, with mutant eNOS rendered resistant to glutathionylation. Ang II effects were nicotinamide adenine dinucleotide phosphate (NADPH) oxidase dependent because preincubation with gp 91ds‐tat, an inhibitor of NADPH oxidase, abolished the increase in eNOS glutathionylation and loss of eNOS activity. Functional significance of glutathionylation in intact vessels was supported by Ang II‐induced impairment of endothelium‐dependent vasorelaxation that was abolished by the disulfide reducing agent, dithiothreitol. Furthermore, attenuation of Ang II signaling in vivo by administration of an angiotensin converting enzyme (ACE) inhibitor reduced eNOS glutathionylation, increased NO, diminished O2•−, improved endothelium‐dependent vasorelaxation and reduced blood pressure. Conclusions Uncoupling of eNOS by glutathionylation is a key mediator of Ang II‐induced endothelial dysfunction, and its reversal is a mechanism for cardiovascular protection by ACE inhibition. We suggest that Ang II‐induced O2•− generation in endothelial cells, although dependent on NADPH oxidase, is amplified by glutathionylation‐dependent eNOS uncoupling. PMID:24755153

  14. Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness.

    PubMed

    Carlsen, Rasmus K; Peters, Christian D; Khatir, Dinah S; Laugesen, Esben; Bøtker, Hans Erik; Winther, Simon; Buus, Niels H

    2016-10-01

    Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients.

  15. Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells

    PubMed Central

    Weikel, Karen A.; Cacicedo, José M.; Ruderman, Neil B.; Ido, Yasuo

    2016-01-01

    High concentrations of glucose and palmitate increase endothelial cell inflammation and apoptosis, events that often precede atherogenesis. They may do so by decreasing basal autophagy and AMP-activated protein kinase (AMPK) activity, although the mechanisms by which this occurs are not clear. Decreased function of the lysosome, an organelle required for autophagy and AMPK, have been associated with hyperactivity of glycogen synthase kinase 3β (GSK3β). To determine whether GSK3β affects nutrient-induced changes in autophagy and AMPK activity, we used a primary human aortic endothelial cell (HAEC) model of type 2 diabetes that we had previously characterized with impaired AMPK activity and autophagy [Weikel et al. (2015) Am. J. Phys. Cell Physiol. 308, C249–C263]. Presently, we found that incubation of HAECs with excess nutrients (25 mM glucose and 0.4 mM palmitate) increased GSK3β activity and impaired lysosome acidification. Suppression of GSK3β in these cells by treatment with a chemical inhibitor or overexpression of kinase-dead GSK3β attenuated these lysosomal changes. Under control and excess nutrient conditions, knockdown of GSK3β increased autophagosome formation, forkhead box protein O1 (FOXO1) activity and AMPK signalling and decreased Akt signalling. Similar changes in autophagy, AMPK and Akt signalling were observed in aortas from mice treated with the GSK3β inhibitor CHIR 99021. Thus, increasing basal autophagy and AMPK activity by inhibiting GSK3β may be an effective strategy in the setting of hyperglycaemia and dyslipidaemia for restoring endothelial cell health and reducing atherogenesis. PMID:27534430

  16. Increased expression of leukotriene C4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm

    PubMed Central

    Di Gennaro, Antonio; Wågsäter, Dick; Mäyränpää, Mikko I.; Gabrielsen, Anders; Swedenborg, Jesper; Hamsten, Anders; Samuelsson, Bengt; Eriksson, Per; Haeggström, Jesper Z.

    2010-01-01

    Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC4, LTD4, and LTE4 are important mediators of asthma, and LTB4 has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC4 synthase (LTC4S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA4 hydrolase, the enzyme responsible for the biosynthesis of LTB4, are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC4S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA4 into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB4. Furthermore, challenge of AAA wall tissue with exogenous LTD4 increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC4S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA. PMID:21078989

  17. Potassium channel openers increase aortic elastic fiber formation and reverse the genetically determined elastin deficit in the BN rat.

    PubMed

    Slove, Séverin; Lannoy, Morgane; Behmoaras, Jacques; Pezet, Mylène; Sloboda, Natacha; Lacolley, Patrick; Escoubet, Brigitte; Buján, Julia; Jacob, Marie-Paule

    2013-10-01

    Hypertension is a cardiovascular disorder that appears in more than half of the patients with Williams-Beuren syndrome, hemizygous for the elastin gene among 26 to 28 other genes. It was shown that the antihypertensive drug minoxidil, an ATP-dependent potassium channel opener, enhances elastic fiber formation; however, no wide clinical application was developed because of its adverse side effects. The Brown Norway rat was used here as an arterial elastin-deficient model. We tested 3 different potassium channel openers, minoxidil, diazoxide, and pinacidil, and 1 potassium channel blocker, glibenclamide, on cultured smooth muscle cells from Brown Norway rat aorta. All tested potassium channel openers increased mRNAs encoding proteins and enzymes involved in elastic fiber formation, whereas glibenclamide had the opposite effect. The higher steady-state level of tropoelastin mRNA in minoxidil-treated cells was attributable to an increase in both transcription and mRNA stability. Treatment of Brown Norway rats for 10 weeks with minoxidil or diazoxide increased elastic fiber content and decreased cell number in the aortic media, without changing collagen content. The minoxidil-induced cardiac hypertrophy was reduced when animals simultaneously received irbesartan, an angiotensin II-receptor antagonist. This side effect of minoxidil was not observed in diazoxide-treated animals. In conclusion, diazoxide, causing less undesirable side effects than minoxidil, or coadministration of minoxidil and irbesartan, increases elastic fiber content, decreases cell number in the aorta and, thus, could be suitable for treating vascular pathologies characterized by diminished arterial elastin content and simultaneous hypertension. PMID:23918751

  18. The antimetastatic drug NAMI-A potentiates the phenylephrine-induced contraction of aortic smooth muscle cells and induces a transient increase in systolic blood pressure.

    PubMed

    Vadori, M; Florio, C; Groppo, B; Cocchietto, M; Pacor, S; Zorzet, S; Candussio, L; Sava, G

    2015-07-01

    The ruthenium-based drug imidazolium trans-imidazoledimethylsulphoxidetetrachlorido ruthenate (NAMI-A) is a novel antitumour drug under clinical evaluation. In this study, NAMI-A is tested on aortic rings in vitro and on the systolic blood pressure in vivo with the aim of evaluating its effects on smooth muscle cells and, more in general, on the vascular system. Pre-incubation of aortic rings with 10 µM NAMI-A for 10 min potentiates the contraction induced by phenylephrine (PE). The reduction of the B max value of [(3)H]-prazosin bound to NAMI-A-treated aortic rings and the ability of NAMI-A to displace [(3)H]-prazosin and [(3)H]-IP3 binding by 25 and 42%, respectively, suggest the involvement of α1-adrenoceptor in mediating the effects on smooth muscle cells. NAMI-A also decreases the number of maximal sites of [(3)H]-prazosin bound to kidney membrane preparation from 34 to 24 fmol/mg proteins. A single i.p. dose (105 mg/kg) or a repeated treatment for 6 consecutive days (17 mg/kg/day) in Wistar rats increases the systolic blood pressure, respectively, 1 h and 3 days after treatment, and the responsiveness of rat aortic rings to PE. Atomic absorption spectroscopy confirms the presence of ruthenium in the aortic rings excised from the treated rats. These findings suggest monitoring the cardiovascular parameters when the drug is used in humans for treating cancer patients, particularly if the drug is associated with chemicals that are potentially active at the cardiovascular level.

  19. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Hwang, Jinah; Sykes, Michelle; Michell, Belinda J.; Kemp, Bruce E.; Lum, Hazel; Jo, Hanjoong

    2002-01-01

    Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

  20. Radiation results in IL-8 mediated intercellular signaling that increases adhesion between monocytic cells and aortic endothelium

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Babitz, Stephen; Dunaway, Chad; Steele, Chad

    Epidemiological evidence has established terrestrial radiation exposure as a risk factor for cardiovascular disease. For example, a major side effect of therapeutic radiation, especially for breast and head-and-neck cancers, is atherosclerosis, which can result in stroke years after treatment. Similarly, atomic bomb survivors were significantly more likely to die of cardiovascular disease than their countrymen. Even radiation technologists, prior to 1950 (when regulations governing shielding and occupational exposure were less rigorous) had an increased risk of clinically significant atherosclerosis. We have recently shown that 600 MeV (56) Fe similarly exacerbates plaque formation in the apoE mouse atherosclerosis model at doses 4-7 fold lower than required for x-rays to produce a similar pro-atherogenic effect. This raises concern that exposure to cosmic radiation might pose a similar risk for astronauts. Because so little is known about the mechanism of pro-atherogenic radiation effects, however, the current strategy to minimize risk from terrestrial radiation sources is to limit exposure. For astronauts on deep space missions, exposure to a significant amount of radiation will be unavoidable. Therefore, an understanding of the mechanism of radiation-induced atherosclerosis will be essential in order to develop countermeasures. Radiation can cause increased adhesiveness of vascular endothelium, leading to inappropriate accumulation of monocytes and other white blood cells, which can initiate a self-perpetuating inflammatory response. This vascular inflammation is an early event in atherosclerosis that can eventually lead to clinically significant cardiovascular events such as myocardial infarction and stroke. We showed earlier that x-rays, (56) Fe, and (28) Si all accelerate development of atherosclerosis in the apoE -/- mouse model. We also demonstrated that both x-rays and heavy ions increase adhesion of monocytic cells to vascular human aortic endothelial

  1. Correlation between pulmonary gas exchange and basal and nitroglycerin (GTN)-induced exhaled nitric oxide (eNO) in patients undergoing cardiac surgery.

    PubMed

    Kövesi, Tamás; Szabo, Anita; Royston, David; Marczin, Nándor

    2005-12-01

    The relationship between eNO and events in the alveolar-capillary unit in acute lung injury remains to be established. Since endogenous eNO largely originates from the airway epithelium, but nitroglycerin (GTN)-induced eNO is due to microvascular/alveolar metabolism, we have proposed to use basal and GTN-induced eNO as metabolic markers of the airway--and microvascular/alveolar function, respectively. The current work investigates the relationship between basal and GTN-induced eNO and oxygenation parameters (PaO(2)/FiO(2) ratio) in patients undergoing cardiac surgery utilising cardiopulmonary bypass (CPB). Breath by breath eNO measurements were made in 10 patients before, and 1 and 3 h after CPB either under basal conditions or following intravenous administration of GTN (1, 2 and 3 microg/kg). Basal eNO remained unchanged, whereas GTN-induced eNO was reduced following CPB. Also, there was a transient reduction in PaO(2)/FiO(2) ratio 1 h after CPB (32+/-4 vs. 44+/-3 kPa). A negative correlation was found between oxygenation and basal eNO by Pearson's correlation test and linear regression analysis suggesting that decreased oxygenation was associated with increased basal eNO. In contrast, a decrease in GTN-induced eNO positively correlated with reduced oxygenation index (R=0.533, p=0.002). These data suggest that differential relationships exist between basal and nitrovasodilator-induced eNO and oxygenation indices during subclinical lung injury in patients following CPB and that GTN-induced eNO evolution may reflect better microvascular events and injury.

  2. Narrowed Aortoseptal Angle Is Related to Increased Central Blood Pressure and Aortic Pressure Wave Reflection.

    PubMed

    Olafiranye, Oladipupo; Ibrahim, Mediha; Kamran, Haroon; Venner-Jones, Kinda; McFarlane, Samy I; Salciccioli, Louis; Lazar, Jason M

    2012-08-01

    The left ventricular (LV) aortoseptal angle (ASA) decreases with age, and is associated with basal septal hypertrophy (septal bulge). Enhanced arterial pressure wave reflection is known to impact LV hypertrophy. We assessed whether ASA is related to central blood pressure (BP) and augmentation index (AI), a measure of the reflected pressure wave. We studied 75 subjects (age 62 ± 16 years; 66% female) who were referred for transthoracic echocardiography and had radial artery applanation tonometry within 24 h. Peripheral systolic BP (P-SBP), peripheral diastolic BP (P-DBP), and peripheral pulse pressure (P-PP) were obtained by sphygmomanometry. Central BPs (C-SBP, C-DBP, C-PP) and AI were derived from applanation tonometry. AI was corrected for heart rate (AI75). The basal septal wall thickness (SWT), mid SWT and ASA were measured using the parasternal long axis echocardiographic view. Mean ASA and AI75 were 117 ± 11° and 22 ± 11%, respectively. ASA correlated with AI75 (r = -0.31, p ≤ 0.01), C-SBP (r = -0.24, p = 0.04), C-PP (r = -0.29, p = 0.01), but only showed a trend towards significance with P-SBP (r = -0.2, p = 0.09) and P-PP (r = -0.21, p = 0.08). Interestingly, C-PP was correlated with basal SWT (r = 0.27, p = 0.02) but not with mid SWT (r = 0.19, p = 0.11). On multivariate linear regression analysis, adjusted for age, gender, weight, and mean arterial pressure, AI75 was an independent predictor of ASA (p = 0.02). Our results suggest that a narrowed ASA is related to increased pressure wave reflection and higher central BP. Further studies are needed to determine whether narrowed LV ASA is a cause or consequence of enhanced wave reflection and whether other factors are involved.

  3. Essentially nonoscillatory (ENO) reconstructions via extrapolation

    NASA Technical Reports Server (NTRS)

    Suresh, Ambady; Jorgenson, Philip C. E.

    1995-01-01

    In this paper, the algorithm for determining the stencil of a one-dimensional Essentially Nonoscillatory (ENO) reconstruction scheme on a uniform grid is reinterpreted as being based on extrapolation. This view leads to another extension of ENO reconstruction schemes to two-dimensional unstructured triangular meshes. The key idea here is to select several cells of the stencil in one step based on extrapolation rather than one cell at a time. Numerical experiments confirm that the new scheme yields sharp nonoscillatory reconstructions and that it is about five times faster than previous schemes.

  4. 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.

  5. Sutureless aortic valve replacement

    PubMed Central

    Phan, Kevin

    2015-01-01

    The increasing incidence of aortic stenosis and greater co-morbidities and risk profiles of the contemporary patient population has driven the development of minimally invasive aortic valve surgery and percutaneous transcatheter aortic valve implantation (TAVI) techniques to reduce surgical trauma. Recent technological developments have led to an alternative minimally invasive option which avoids the placement and tying of sutures, known as “sutureless” or rapid deployment aortic valves. Potential advantages for sutureless aortic prostheses include reducing cross-clamp and cardiopulmonary bypass (CPB) duration, facilitating minimally invasive surgery and complex cardiac interventions, whilst maintaining satisfactory hemodynamic outcomes and low paravalvular leak rates. However, given its recent developments, the majority of evidence regarding sutureless aortic valve replacement (SU-AVR) is limited to observational studies and there is a paucity of adequately-powered randomized studies. Recently, the International Valvular Surgery Study Group (IVSSG) has formulated to conduct the Sutureless Projects, set to be the largest international collaborative group to investigate this technology. This keynote lecture will overview the use, the potential advantages, the caveats, and current evidence of sutureless and rapid deployment aortic valve replacement (AVR). PMID:25870807

  6. 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.

  7. Genetics, Pregnancy, and Aortic Degeneration.

    PubMed

    Crawford, Jeffrey D; Hsieh, Cindy M; Schenning, Ryan C; Slater, Matthew S; Landry, Gregory J; Moneta, Gregory L; Mitchell, Erica L

    2016-01-01

    We present a case of familial thoracic aortic aneurysm and dissection (FTAAD) in a pregnant female. FTAAD is an inherited, nonsyndromic aortopathy resulting from several genetic mutations critical to aortic wall integrity have been identified. One such mutation is the myosin heavy chain gene (MYH11) which is responsible for 1-2% of all FTAAD cases. This mutation results in aortic medial degeneration, loss of elastin, and reticulin fiber fragmentation predisposing to TAAD. Aortic disease is more aggressive during pregnancy as a result of increased wall stress from hyperdynamic cardiovascular changes and estrogen-induced aortic media degeneration. Our patient was a 29-year-old G2P1 woman at 26 weeks gestation presenting with abdominal and back pain. Work-up revealed a 6.4-cm ascending aortic aneurysm with a type A dissection extending into all arch vessels, aortic coarctation at the isthmus, and a separate focal type B aortic dissection with visceral involvement. Surgical management included concomitant cesarean section with delivery of a live premature infant, tubal ligation, ascending aortic replacement with reconstruction of the arch vessels, and aortic valve resuspension. The type B dissection was managed medically without complication. This is the first reported case of aortic dissection in a patient with FTAAD/MYH11 mutation and pregnancy. This case highlights that FTAAD and pregnancy cause aortic degeneration via distinct mechanisms and that hyperdynamics of pregnancy increase aortic wall stress. Management of pregnancy associated with aortopathy requires early transfer to a tertiary center, careful investigation to identify familial aortopathy, fetal monitoring, and a multidisciplinary team approach. PMID:26381327

  8. SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

    PubMed Central

    Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

    2016-01-01

    Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

  9. Intra-aortic balloon pumping reduces the increased arterial load caused by acute cardiac depression, modifying central and peripheral load determinants in a time- and flow-related way.

    PubMed

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

    2012-09-01

    The mechanisms that explain intra-aortic balloon pumping (IABP) effects are not completely understood, and attributing them only to pressure-associated changes in cardiac function would be an oversimplification. Since IABP modifies the aortic and systemic blood-flow pattern, flow-related effects could be expected. To characterize effects of acute heart failure (AHF) on the arterial biomechanics; IABP effects on the arterial biomechanics during AHF, and their potential time-dependence; the association between hemodynamics and biomechanical changes during AHF and IABP. Sheep (n = 6) aortic pressure, flow, and diameter were measured: (1) before (Basal) and (2) 1-3 (HF(1-3)) and 28-30 (HF(28-30)) min after starting halothane to induce AHF; and (3) at specific times (1-3, 14-15 and 28-30 min) during IABP assistance. Calculus: aortic characteristic impedance (Z(c)), beta stiffness (β), incremental (E(INC)) and pressure-strain elastic modulus (E(P)); total arterial compliance (C(G)), total systemic vascular resistance and wave propagation parameters. (1) AHF resulted in an acute increase in aortic and systemic stiffness (HF(28-30) % changes with respect to Basal conditions: β +217%, E (P) +143%, E(INC) +101%, Z(c) +52%, C(G) -13%), associated with the reduction in the aortic blood flow; (2) during AHF IABP resulted in acute beneficial changes aortic and systemic biomechanics (% changes in IABP(1-3) with respect HF(28-30): β -62%, E(P) -68%, E (INC) -66%, Z(c) -38%, C(G) 66%), and in wave propagation parameters, (3) IABP-related changes were time-dependent and associated with changes in aortic blood flow. Aortic and systemic biomechanical and impedance properties are detrimentally modified during AHF, being the changes rapidly reverted during IABP. IABP-related beneficial changes in arterial biomechanics were time-dependent and associated with IABP capability to increase blood flow.

  10. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function

    PubMed Central

    Chen, Chun-An; Wang, Tse-Yao; Varadharaj, Saradhadevi; Reyes, Levy A.; Hemann, Craig; Hassan Talukder, M. A.; Chen, Yeong-Renn; Druhan, Lawrence J.; Zweier, Jay L.

    2012-01-01

    Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O2•−), which are key mediators of cellular signalling. In the presence of Ca2+/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from L-arginine (L-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH4) and L-Arg1–3. In the absence of BH4, NO synthesis is abrogated and instead O2•− is generated4–7. While NOS dysfunction occurs in diseases with redox stress, BH4 repletion only partly restores NOS activity and NOS-dependent vasodilation7. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation8,9. Under oxidative stress, S-glutathionylation occurs through thiol–disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione10,11. Cysteine residues are critical for the maintenance of eNOS function12,13; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O2•− generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O2•− generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol

  11. Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr−/− mice expressing CETP*s⃞

    PubMed Central

    Hime, Neil J.; Black, Audrey S.; Bulgrien, Josh J.; Curtiss, Linda K.

    2008-01-01

    In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages. The combined actions of these proteins have profound effects on HDL structure and function. It is not known how these HDL changes influence atherosclerosis. To elucidate the role of leukocyte-derived HL on atherosclerosis in a background of CETP expression, we studied low density lipoprotein receptor-deficient mice expressing human CETP (CETPtgLDLr−/−) with a leukocyte-derived HL deficiency (HL−/− BM). HL−/− bone marrow (BM), CETPtgLDLr−/− mice were generated via bone marrow transplantation. Wild-type bone marrow was transplanted into CETPtgLDLr−/− mice to generate HL+/+ BM, CETPtgLDLr−/− controls. The chimeras were fed a high-fat, high-cholesterol diet for 14 weeks to promote atherosclerosis. In female HL−/− BM, CETPtgLDLr−/− mice plasma HDL-cholesterol concentration during high-fat feeding was decreased 27% when compared with HL+/+ BM, CETPtgLDLr−/− mice (P < 0.05), and this was associated with a 96% increase in en face aortic atherosclerosis (P < 0.05). In male CETPtgLDLr−/− mice, leukocyte-derived HL deficiency was associated with a 16% decrease in plasma HDL-cholesterol concentration and a 25% increase in aortic atherosclerosis. Thus, leukocyte-derived HL in CETPtgLDLr−/− mice has an atheroprotective role that may involve increased HDL levels. PMID:18599739

  12. Aortic Aneurysm Statistics

    MedlinePlus

    ... Blood Pressure Salt Cholesterol Million Hearts® WISEWOMAN Aortic Aneurysm Fact Sheet Recommend on Facebook Tweet Share Compartir ... cause of most deaths from aortic aneurysms. Aortic Aneurysm in the United States Aortic aneurysms were the ...

  13. Abdominal Aortic Aneurysm (AAA)

    MedlinePlus

    ... Resources Professions Site Index A-Z Abdominal Aortic Aneurysm (AAA) Abdominal aortic aneurysm (AAA) occurs when atherosclerosis ... aortic aneurysm treated? What is an abdominal aortic aneurysm? The aorta, the largest artery in the body, ...

  14. 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 ...

  15. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients.

    PubMed

    Altun, Ibrahim; Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-06-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm(2) ·dyn(-1); P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients.

  16. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients

    PubMed Central

    Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-01-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm2·dyn−1; P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients. PMID:27303237

  17. Aortic Aneurysm

    MedlinePlus

    ... these occur in the part of the aorta running through the chest Abdominal aortic aneurysms (AAA) - these occur in the part of the aorta running through the abdomen Most aneurysms are found during ...

  18. Aortic dissection.

    PubMed

    Nienaber, Christoph A; Clough, Rachel E; Sakalihasan, Natzi; Suzuki, Toru; Gibbs, Richard; Mussa, Firas; Jenkins, Michael T; Thompson, Matt M; Evangelista, Arturo; Yeh, James S M; Cheshire, Nicholas; Rosendahl, Ulrich; Pepper, John

    2016-01-01

    Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation (dissection) of the layers of the aortic wall. Aortic dissection is most common in those 65-75 years of age, with an incidence of 35 cases per 100,000 people per year in this population. Other risk factors include hypertension, dyslipidaemia and genetic disorders that involve the connective tissue, such as Marfan syndrome. Swift diagnostic confirmation and adequate treatment are crucial in managing affected patients. Contemporary management is multidisciplinary and includes serial non-invasive imaging, biomarker testing and genetic risk profiling for aortopathy. The choice of approach for repairing or replacing the damaged region of the aorta depends on the severity and the location of the dissection and the risks of complication from surgery. Open surgical repair is most commonly used for dissections involving the ascending aorta and the aortic arch, whereas minimally invasive endovascular intervention is appropriate for descending aorta dissections that are complicated by rupture, malperfusion, ongoing pain, hypotension or imaging features of high risk. Recent advances in the understanding of the underlying pathophysiology of aortic dissection have led to more patients being considered at substantial risk of complications and, therefore, in need of endovascular intervention rather than only medical or surgical intervention. PMID:27440162

  19. Aortic stenting.

    PubMed

    Droc, Ionel; Calinescu, Francisca Blanca; Droc, Gabriela; Blaj, Catalin; Dammrau, Rolf

    2015-01-01

    The approach to aortic pathology is nowadays more and more endovascular at both thoracic and abdominal levels. Thoracic stenting has gained worldwide acceptance as first intention to treat pathologies of the descending thoracic aorta. Indications have been extended to aortic arch aneurysms and also to diseases of the ascending aorta. The current devices in use for thoracic endovascular repair (TEVAR) are Medtronic Valiant, Gore TAG, Cook Tx2 and Jotec. The choice of the endograft depends on the thoracic aortic pathology and the anatomical suitability. The technological evolution of the abdominal aortic endografts was very rapid, arriving now at the fourth generation. We report the results of 55 elective cases of endovascular abdominal aortic repair (EVAR) performed in two vascular surgical centers in Romania and Germany. The prostheses used were 16 E-vita Abdominal XT, 12 Excluder, eight Talent, seven PowerLink, three Endurant and nine custom-made, fenestrated or branched from Jotec. The mean follow-up was 18 months with CT-scan, duplex ultrasound and contrast-enhanced ultrasound. The mortality was 2%. EVAR tends to become the gold standard for abdominal aortic aneurysm repair. Technological development of the devices with lowest profile introduction systems will permit to extend the anatomical indications to new frontiers. PMID:26200430

  20. The role of transesophageal echocardiography in aortic surgery.

    PubMed

    Nowak-Machen, Martina

    2016-09-01

    Aortic disease, when left untreated, is still associated with major morbidity and mortality. Aortic dissection and aortic aneurysm are the main reasons for performing aortic surgery procedures in the adult. Imaging techniques such as computed tomography and magnetic resonance imaging play a key role in the preoperative evaluation. Transesophageal echocardiography (TEE) has become a safe and invaluable perioperative imaging tool for aortic disease over the past decade with high sensitivity and specificity. TEE can increase patient safety and improve overall patient outcome in aortic surgery. Especially during endovascular aortic repair, TEE is more sensitive than other imaging modalities in diagnosing complications such as graft endoleaks. Newer echocardiographic techniques such as three-dimensional (3D) TEE and contrast-enhanced TEE are emerging and seem to have a valuable role especially in aortic dissection repair and endovascular aortic stent procedures. In the absence of contraindications, TEE should generally be performed during aortic surgery and endovascular aortic procedures. PMID:27650342

  1. 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

  2. Surgical repair for aortic dissection accompanying a right-sided aortic arch.

    PubMed

    Obitsu, Yukio; Koizumi, Nobusato; Iwahashi, Toru; Saiki, Naozumi; Shigematsu, Hiroshi

    2010-01-01

    Aortic anomaly in which a right-sided aortic arch associated with Kommerell's diverticulum and aberrant left subclavian artery is rare. The present report describes a patient with type-B aortic dissection accompanying aortic anomalies consisting of right-sided aortic arch and the left common carotid and left subclavian artery arising from Kommerell's diverticulum. As dissecting aortic aneurysm diameter increased rapidly, Single-stage surgical repair of extensive thoracic aorta was performed through median sternotomy and right posterolateral fifth intercostal thoracotomy, yielding favorable results. Our surgical procedures are discussed.

  3. Surgical repair for aortic dissection accompanying a right-sided aortic arch

    PubMed Central

    2010-01-01

    Aortic anomaly in which a right-sided aortic arch associated with Kommerell's diverticulum and aberrant left subclavian artery is rare. The present report describes a patient with type-B aortic dissection accompanying aortic anomalies consisting of right-sided aortic arch and the left common carotid and left subclavian artery arising from Kommerell's diverticulum. As dissecting aortic aneurysm diameter increased rapidly, Single-stage surgical repair of extensive thoracic aorta was performed through median sternotomy and right posterolateral fifth intercostal thoracotomy, yielding favorable results. Our surgical procedures are discussed. PMID:20459743

  4. Balloon aortic valvuloplasty as a bridge to aortic valve surgery for severe aortic stenosis.

    PubMed

    Nwaejike, Nnamdi; Mills, Keith; Stables, Rod; Field, Mark

    2015-03-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, in patients with severe aortic stenosis, can balloon valvuloplasty be used as a bridge to aortic valve replacement? Altogether 463 papers were found using the reported search, of which 11 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that balloon aortic valvuloplasty is recommended as a bridge to aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI) in patients with severe symptomatic aortic stenosis. Institutional practices, local and logistic factors can affect patient selection and management approaches to severe aortic stenosis, but having the facility to offer balloon aortic valvuloplasty (especially in the TAVI era) provides another management option for patients who would otherwise have been considered unacceptably high risk for aortic valve surgery. The increased incidence of balloon aortic valvuloplasty mirrors the increase in the use of TAVI with a sharp increase in activity from 2006. Success rates for bridging from balloon aortic valvuloplasty to definite surgical intervention are in the range 26.3-74%, with AVR or TAVI occurring within 8 weeks to 7 months. Complications from balloon aortic valvuloplasty such as aortic regurgitation (AR) can be managed successfully. Up to 40% of patients selected by balloon aortic valvuloplasty to have TAVI or AVR do not have these procedures within 2 years. While most of these patients are excluded for objective clinical reasons such as terminal disease/malignancy or other persistent contraindication, some patients refuse definitive treatment and others die while on the waiting list. Outcomes in patients bridged to AVR/TAVI are better than in patients treated with balloon aortic valvuloplasty

  5. 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.

  6. Management of Acute Aortic Syndrome and Chronic Aortic Dissection

    SciTech Connect

    Nordon, Ian M. Hinchliffe, Robert J.; Loftus, Ian M.; Morgan, Robert A.; Thompson, Matt M.

    2011-10-15

    Acute aortic syndrome (AAS) describes several life-threatening aortic pathologies. These include intramural hematoma, penetrating aortic ulcer, and acute aortic dissection (AAD). Advances in both imaging and endovascular treatment have led to an increase in diagnosis and improved management of these often catastrophic pathologies. Patients, who were previously consigned to medical management or high-risk open surgical repair, can now be offered minimally invasive solutions with reduced morbidity and mortality. Information from the International Registry of Acute Aortic Dissection (IRAD) database demonstrates how in selected patients with complicated AAD the 30-day mortality from open surgery is 17% and endovascular stenting is 6%. Despite these improvements in perioperative deaths, the risks of stroke and paraplegia remain with endovascular treatment (combined outcome risk 4%). The pathophysiology of each aspect of AAS is described. The best imaging techniques and the evolving role of endovascular techniques in the definitive management of AAS are discussed incorporating strategies to reduce perioperative morbidity.

  7. Ganoderma atrum polysaccharide improves aortic relaxation in diabetic rats via PI3K/Akt pathway.

    PubMed

    Zhu, Ke-Xue; Nie, Shao-Ping; Li, Chuan; Gong, Deming; Xie, Ming-Yong

    2014-03-15

    A newly identified polysaccharide (PSG-1) has been purified from Ganoderma atrum. The study was to investigate the protective effect of PSG-1 on diabetes-induced endothelial dysfunction in rat aorta. Rats were fed a high fat diet for 8 weeks and then injected with a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were orally treated with PSG-1 for 4 weeks. It was found that administration of PSG-1 significantly reduced levels of fasting blood glucose, improved endothelium-dependent aortic relaxation, increased levels of phosphoinositide 3-kinase (PI3K), phospho-Akt (p-Akt), endothelial nitric oxide synthase (eNOS) and nitric oxide in the aorta from diabetic rats, compared to un-treated diabetics. These results suggested that the protective effects of PSG-1 against endothelial dysfunction may be related to activation of the PI3K/Akt/eNOS pathway.

  8. 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

    2009-01-01

    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 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. PMID:19654415

  9. 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.

  10. [Thoracoabdominal aortic aneurysm].

    PubMed

    Kalder, J; Kotelis, D; Jacobs, M J

    2016-09-01

    Thoracoabdominal aortic aneurysms (TAAA) are rare events with an incidence of 5.9 cases per 100,000 persons per year. In Germany approximately 940 TAAA procedures are performed annually. The cause of TAAA is mostly degenerative but they can also occur on the basis of an aortic dissection or connective tissue disease (e. g. Marfan's syndrome). Patients often have severe comorbidities and suffer from hypertension, coronary heart disease or chronic obstructive pulmonary disease, mostly as a result of smoking. Operative treatment is indicated when the maximum aortic diameter has reached 6 cm (> 5 cm in patients with connective tissue disease) or the aortic diameter rapidly increases (> 5 mm/year). Treatment options are open surgical aortic repair with extracorporeal circulation, endovascular repair with branched/fenestrated endografts and parallel grafts (chimneys) or a combination of open and endovascular procedures (hybrid procedures). Mortality rates after both open and endovascular procedures are approximately 8 % depending on the extent of the repair. Furthermore, there are relevant risks of complications, such as paraplegia (up to 20 %) and the necessity for dialysis. In recent years several approaches to minimize these risks have been proposed. Besides cardiopulmonary risk evaluation, clinical assessment of patients by the physician with respect to the patient-specific anatomy influences the allocation of patients to one treatment option or another. Surgery of TAAA should ideally be performed in high-volume centers in order to achieve better results. PMID:27558261

  11. Regular Cocaine Use Is Associated with Increased Systolic Blood Pressure, Aortic Stiffness and Left Ventricular Mass in Young Otherwise Healthy Individuals

    PubMed Central

    Kozor, Rebecca; Grieve, Stuart M.; Buchholz, Stefan; Kaye, Sharlene; Darke, Shane; Bhindi, Ravinay; Figtree, Gemma A.

    2014-01-01

    Background The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves ‘social’ users is not well established. Methods/Results Twenty regular cocaine users and 20 control subjects were recruited by word-of-mouth. Cardiovascular magnetic resonance was performed to assess cardiac and vascular structure and function. Cocaine users had higher systolic blood pressure compared to non-users (134±11 vs 126±11 mmHg, p = 0.036), a finding independent of age, body surface area, smoking and alcohol consumption. Cocaine use was associated with increased arterial stiffness - reflected by reduced aortic compliance (1.3±0.2 vs 1.7±0.5 cm2×10−2.mmHg−1, p = 0.004), decreased distensibility (3.8±0.9 vs 5.1±1.4 mmHg−1.10−3, p = 0.001), increased stiffness index (2.6±0.6 vs 2.1±0.6, p = 0.005), and higher pulse wave velocity (5.1±0.6 vs 4.4±0.6 m.s−1, p = 0.001). This change in aortic stiffness was independent of vessel wall thickness. Left ventricular mass was 18% higher in cocaine users (124±25 vs 105±16 g, p = 0.01), a finding that was independent of body surface area, and left atrial diameter was larger in the user group than controls (3.8±0.6 vs 3.5±0.3 cm, p = 0.04). The increased left ventricular mass, systolic blood pressure and vascular stiffness measures were all associated with duration and/or frequency of cocaine use. No late gadolinium enhancement or segmental wall motion abnormalities were seen in any of the subjects. Conclusions Compared with the non-user control cohort, cocaine users had increased aortic stiffness and systolic blood pressure, associated with greater left ventricular mass. These measures are all well known risk factors for premature cardiovascular events, highlighting the dangers of cocaine use, even in a ‘social’ setting, and have important public health implications. PMID:24717541

  12. Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2

    PubMed Central

    Wang, Chunmao; Qian, Xiangyang; Sun, Xiaogang

    2015-01-01

    Increased levels of angiotensin II (Ang II) and activated matrix metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human ASMCs) have recently been implicated in the pathogenesis of thoracic aortic aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA development in Marfan Syndrome. However, there is scant data regarding the relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we investigated the effect of Ang II on MMP-2 expression in human ASMCs and used Western blotting to identify the Ang II receptors and intracellular signaling pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence data demonstrated that Ang II receptors were expressed on human ASMCs. Additionally, Ang II increased the expression of Ang II type 2 receptor (AT2R) but not AT1R at both the transcriptional and translational levels. Furthermore, Western blotting showed that Ang II increased MMP-2 expression in human ASMCs in a dose- and time-dependent manner. This response was completely inhibited by the AT1R inhibitor candesartan but not by the AT2R blocker PD123319. In addition, Ang II–induced upregulation of MMP-2 was mediated by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In conclusion, these results indicate that Ang II can increase the expression of MMP-2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that antagonists of AT1R and ERK1/2 may be useful for treating TAAs. PMID:25767191

  13. Aortic biomechanics in hypertrophic cardiomyopathy

    PubMed Central

    Badran, Hala Mahfouz; Soltan, Ghada; Faheem, Nagla; Elnoamany, Mohamed Fahmy; Tawfik, Mohamed; Yacoub, Magdi

    2015-01-01

    Background: Ventricular-vascular coupling is an important phenomenon in many cardiovascular diseases. The association between aortic mechanical dysfunction and left ventricular (LV) dysfunction is well characterized in many disease entities, but no data are available on how these changes are related in hypertrophic cardiomyopathy (HCM). Aim of the work: This study examined whether HCM alone is associated with an impaired aortic mechanical function in patients without cardiovascular risk factors and the relation of these changes, if any, to LV deformation and cardiac phenotype. Methods: 141 patients with HCM were recruited and compared to 66 age- and sex-matched healthy subjects as control group. Pulse pressure, aortic strain, stiffness and distensibility were calculated from the aortic diameters measured by M-mode echocardiography and blood pressure obtained by sphygmomanometer. Aortic wall systolic and diastolic velocities were measured using pulsed wave Doppler tissue imaging (DTI). Cardiac assessment included geometric parameters and myocardial deformation (strain and strain rate) and mechanical dyssynchrony. Results: The pulsatile change in the aortic diameter, distensibility and aortic wall systolic velocity (AWS') were significantly decreased and aortic stiffness index was increased in HCM compared to control (P < .001) In HCM AWS' was inversely correlated to age(r = − .32, P < .0001), MWT (r = − .22, P < .008), LVMI (r = − .20, P < .02), E/Ea (r = − .16, P < .03) LVOT gradient (r = − 19, P < .02) and severity of mitral regurg (r = − .18, P < .03) but not to the concealed LV deformation abnormalities or mechanical dyssynchrony. On multivariate analysis, the key determinant of aortic stiffness was LV mass index and LVOT obstruction while the role LV dysfunction in aortic stiffness is not evident in this population. Conclusion: HCM is associated with abnormal aortic mechanical properties. The severity of cardiac

  14. Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis.

    PubMed

    Sung, J H; Lee, B E; Kim, J O; Jeon, Y J; Kim, S H; Lim, S W; Moon, J Y; Cha, D H; Kim, O J; Kim, I J; Kim, N K

    2015-01-01

    Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk. PMID:26662450

  15. Alpha(1)-adrenergic-mediated eNOS phosphorylation in intact arteries.

    PubMed

    Looft-Wilson, Robin C; Todd, Sarah E; Araj, Christina A; Mutchler, Stephanie M; Goodell, Cara A Raphael

    2013-01-01

    Activation of arterial smooth muscle alpha(1)-adrenergic receptors results in vasoconstriction, as well as a secondary release of nitric oxide and slow vasodilation, presumably through gap junction communication from smooth muscle to endothelium. We hypothesized that this slow vasodilation is due to activation of eNOS through phosphorylation at Ser1179 and dephosphorylation at Thr495. Phosphorylation was measured by western blot using mouse mesenteric arteries that were cannulated and pressurized (75 mm Hg) and treated either by 1) 5 min of phenylephrine superfusion (10(-5)M) (PE5), 2) 15 min of phenylephrine (PE15), 3) 15 min phenylephrine followed by acetylcholine (10(-4)M) (PE+ACh), or 4) 20 min time control with no treatment (NT) [4-5 arteries pooled per treatment per blot; 5 blots performed]. These treatments allowed correlation between vasomotor changes, namely maximal constriction (PE5), slow vasodilation (PE15), and maximal dilation (PE+ACh), and relative phosphorylation changes. Phosphorylation of eNOS at Ser1179 was increased relative to NT by more than 2-fold at PE5 and remained similarly increased at PE15 and PE+ACh. Phosphorylation of eNOS at Thr495 was less in all treatments relative to NT, but not significantly. Treatment with L-NAME (10(-4)M) or endothelial denudation indicated that the slow dilation in response to phenylephrine was completely due to nitric oxide synthase and was endothelial dependent. These results indicate that eNOS phosphorylation at Ser1179 occurs before the slow dilation and is not actively involved in this vasodilation or dilation to acetylcholine, but may play a permissive role in eNOS activation by other mechanisms. It is not yet known what mechanism is responsible for Ser1179 phosphorylation with phenylephrine stimulation.

  16. Ablation of eNOS does not promote adipose tissue inflammation.

    PubMed

    Jurrissen, Thomas J; Sheldon, Ryan D; Gastecki, Michelle L; Woodford, Makenzie L; Zidon, Terese M; Rector, R Scott; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-04-15

    Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, 10-wk-old C57BL6 wild-type and endothelial nitric oxide synthase (eNOS) knockout male mice were randomized to either a control diet (10% kcal from fat) or a Western diet (44.9% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 wk (n= 7 or 8/group). In wild-type mice, Western diet-induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNF-α, and CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs, and Mac-2 protein), as well as reduced markers of mitochondrial content (e.g., OXPHOS complex I and IV protein). Unexpectedly, these effects of Western diet on visceral white AT were not accompanied by decreases in eNOS phosphorylation at Ser-1177 or increases in eNOS phosphorylation at Thr-495. Also counter to expectations, eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared with wild-type mice. Collectively, these findings do not support the hypothesis that reduced NO production from eNOS contributes to obesity-related AT inflammation. PMID:26864812

  17. 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

  18. Whole-body vibration attenuates the increase in leg arterial stiffness and aortic systolic blood pressure during post-exercise muscle ischemia.

    PubMed

    Figueroa, Arturo; Gil, Ryan; Sanchez-Gonzalez, Marcos A

    2011-07-01

    Exercise with whole-body vibration (WBV) decreases brachial-ankle pulse wave velocity (baPWV), a marker of systemic arterial stiffness. To examine the effect of WBV on arterial responses, 12 young men underwent three experimental trials: (1) no-exercise control (CON), (2) static squat with WBV, and (3) static squat without WBV (no-WBV). Bilateral baPWV and femoral-ankle PWV (faPWV), carotid-femoral PWV (cfPWV), augmentation index (AIx), first (P1) and second (P2) systolic peaks, aortic systolic blood pressure (aSBP), and heart rate (HR) were assessed at rest, during 4-min post-exercise muscle ischemia (PEMI) on the left thigh, and 4-min recovery. During PEMI, right faPWV increased (P < 0.05) after no-WBV and did not change after CON and WBV. Right baPWV, P2, and aSBP increased (P < 0.05) after both exercise trials, but the increase was lower (P < 0.05) after WBV than no-WBV. The increases in cfPWV (P < 0.05), AIx (P < 0.05), P1 (P < 0.01), and HR (P < 0.05) were similar in both trials during PEMI. During recovery, right faPWV and baPWV remained similar than rest after WBV and CON, but remained elevated (P < 0.05) after no-WBV. Aortic SBP, P1, and P2 remained elevated (P < 0.05) in both exercise trials during recovery, but the levels were lower (P < 0.05) than PEMI. Left faPWV and baPWV were reduced (P < 0.05) from rest in the three trials. CfPWV, AIx, and HR returned to resting levels in both exercises. WBV prevents the increases in faPWV and attenuates the increase in baPWV and aSBP induced by post-static squat muscle ischemia due to an attenuated P2 response.

  19. [Remote results of reimplantation of the aortic valve in patients with ascending aortic aneurysm accompanied by aortic insufficiency].

    PubMed

    Cherniavskiĭ, A M; Al'sov, S A; Sirota, D A; Khvan, D S; Liashenko, M M; Ponomarev, D N; Kadyrbaev, D Zh

    2015-01-01

    Valve-sparing operations on the aorta has recently been gaining ever increasing popularity due to more detailed study of physiology of the aortic root, as well as promising mid- and long-term results. The world practice uses various techniques making it possible to remove both ascending aortic aneurysm and aortic valve insufficiency. The authors herein describe and analyse their experience in performing reimplantation of the aortic valve in patients with ascending aortic aneurysm and concomitant aortic insufficiency. Specialists of the clinic of the Novosibirsk Scientific Research Institute for Circulatory Pathology during the period from 2003 to 2013 performed a total of 77 operations of reimplantation of the aortic valve in patients with ascending aortic aneurysm and pronounced aortic valve insufficiency. The majority of patients were men (57 males and 20 females), mean age 53.1±12.2 years (range 21-72). 80% of cases had NYHA functional class II-III circulatory insufficiency (degree 2.3±0.7). Preoperative examination revealed in the majority of patients (97.4%) moderate-to-severe aortic valve insufficiency and ascending aortic aneurysm. All patients underwent reimplantation of the aortic valve. The duration of artificial circulation amounted to 202.4±33 minutes, with the average time of aortic occlusion being 164±28 min. Accompanying procedures (annuloplasty of the mitral valve and/or coronary aortic bypass grafting) were performed in 12 (15.6%) cases. Additional plasty of valvular cusps was carried out in 9 (11.7%) patients, with rethoracotomy required in 5 (6.4%) cases due to haemorrhage. The average period of follow up amounted to 53.3±8.5 (3-115) months. During this time total survival amounted to 91%, with freedom from aortic valve prosthetic repair equalling 93%. The obtained findings suggest that aortic valve reimplantation into the prosthesis is a safe intervention and associated with a comparatively low level of operative lethality. Moderate aortic

  20. (−)-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

  1. Minimally invasive aortic valve surgery

    PubMed Central

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-01-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  2. Minimally invasive aortic valve surgery.

    PubMed

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-09-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  3. Aortic Valve Disease

    MedlinePlus

    ... Disease Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that ... Disease Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Aortic Valve Disease Overview The human heart has ...

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

    PubMed

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

    2016-03-01

    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 N(ω)-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.

  5. 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

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

    PubMed

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

    2016-03-01

    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 N(ω)-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

  7. Myxomavirus anti-inflammatory chemokine binding protein reduces the increased plaque growth induced by chronic Porphyromonas gingivalis oral infection after balloon angioplasty aortic injury in mice.

    PubMed

    Lucas, Alexandra R; Verma, Raj K; Dai, Erbin; Liu, Liying; Chen, Hao; Kesavalu, Sheela; Rivera, Mercedes; Velsko, Irina; Ambadapadi, Sriram; Chukkapalli, Sasanka; Kesavalu, Lakshmyya

    2014-01-01

    Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virus-derived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE-/- mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P<0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P<0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE-/- mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine

  8. Serum from Calorie-Restricted Rats Activates Vascular Cell eNOS through Enhanced Insulin Signaling Mediated by Adiponectin

    PubMed Central

    Cerqueira, Fernanda M.; Brandizzi, Laura I.; Cunha, Fernanda M.; Laurindo, Francisco R. M.; Kowaltowski, Alicia J.

    2012-01-01

    eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO• signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR. PMID:22319612

  9. MDCT evaluation of acute aortic syndrome (AAS).

    PubMed

    Valente, Tullio; 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

  10. [ENDOVASCULAR ABDOMINAL AORTIC ANEURISM REPAIR].

    PubMed

    Maĭstrenko, D N; Generalov, M I; Tarazov, P G; Zherebtsov, F K; Osovskikh, V V; Ivanov, A S; Oleshchuk, A N; Granov, D A

    2015-01-01

    The authors analyzed the single-center experience of treatment of 72 patients with abdominal aortic aneurisms and severe accompanied pathology. The aneurisms were repaired by stent-grafts. All the patients had abdominal aortic aneurisms with the diameters from 41 to 84 mm against the background of severe somatic pathology. It was a contraindication to planned open surgery. An installation of stent-graft was successful in all 72 follow-ups. It wasn't necessary to use a conversion to open surgery. The follow-up period consisted of 44,6?2,1 months. Control ultrasound and computer tomography studies hadn't revealed an increase of aneurism sack sizes or "eakages". A reduction of abdominal aortic aneurism sizes was noted in 37 patients on 4-5% during first year after operation. The stent-graft implantation extends the possibilities of abdominal aortic aneurism treatment for patients from a high surgical risk group. PMID:26234059

  11. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells.

    PubMed

    Spigoni, Valentina; Mena, Pedro; Cito, Monia; Fantuzzi, Federica; Bonadonna, Riccardo C; Brighenti, Furio; Dei Cas, Alessandra; Del Rio, Daniele

    2016-08-02

    The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MS(n). The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism.

  12. Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells.

    PubMed

    Spigoni, Valentina; Mena, Pedro; Cito, Monia; Fantuzzi, Federica; Bonadonna, Riccardo C; Brighenti, Furio; Dei Cas, Alessandra; Del Rio, Daniele

    2016-01-01

    The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MS(n). The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism. PMID:27490528

  13. Vascular nitric oxide: Beyond eNOS.

    PubMed

    Zhao, Yingzi; Vanhoutte, Paul M; Leung, Susan W S

    2015-10-01

    As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA) or production of cyclic inosine monophosphate (cIMP)] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS) but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis. PMID:26499181

  14. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2.

    PubMed

    Ramesh, Sangeetha; Morrell, Craig N; Tarango, Cristina; Thomas, Gail D; Yuhanna, Ivan S; Girardi, Guillermina; Herz, Joachim; Urbanus, Rolf T; de Groot, Philip G; Thorpe, Philip E; Salmon, Jane E; Shaul, Philip W; Mineo, Chieko

    2011-01-01

    In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to β2 glycoprotein I (β2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms. Here we show that in mice both of these processes are caused by the inhibition of eNOS. In studies of cultured human, bovine, and mouse endothelial cells, the promotion of monocyte adhesion by aPL entailed decreased bioavailable NO, and aPL fully antagonized eNOS activation by diverse agonists. Similarly, NO-dependent, acetylcholine-induced increases in carotid vascular conductance were impaired in aPL-treated mice. The inhibition of eNOS was caused by antibody recognition of domain I of β2GPI and β2GPI dimerization, and it was due to attenuated eNOS S1179 phosphorylation mediated by protein phosphatase 2A (PP2A). Furthermore, LDL receptor family member antagonism with receptor-associated protein (RAP) prevented aPL inhibition of eNOS in cell culture, and ApoER2-/- mice were protected from aPL inhibition of eNOS in vivo. Moreover, both aPL-induced increases in leukocyte-endothelial cell adhesion and thrombus formation were absent in eNOS-/- and in ApoER2-/- mice. Thus, aPL-induced leukocyte-endothelial cell adhesion and thrombosis are caused by eNOS antagonism, which is due to impaired S1179 phosphorylation mediated by β2GPI, apoER2, and PP2A. Our results suggest that novel therapies for APS can now be developed targeting these mechanisms. PMID:21123944

  15. Phenylephrine activates eNOS Ser 1177 phosphorylation and nitric oxide signaling in renal hypertensive rat aorta.

    PubMed

    Silva, Bruno R; Pernomian, Laena; Grando, Marcella D; Bendhack, Lusiane M

    2014-09-01

    The endothelial nitric oxide synthase (eNOS) plays an important role in the control of the vascular tone. This work aimed to evaluate the role of an α1-adrenoceptor agonist phenylephrine (PE) on eNOS activity and downstream signaling pathway activation in normotensive (2K) and renal hypertensive (2K-1C) intact-endothelium rat aortas. Concentration-effect curves were performed for PE in intact-endothelium aortas from 2K and 2K-1C rats, in the absence of or in the presence of NOS or soluble guanylyl cyclase (sGC) inhibitor. Intact endothelium aortas were stimulated with PE in organ chambers and eNOS Ser(1177)/Thr(495) phosphorylation expression was evaluated by western blot. Nitric Oxide (NO) production was evaluated in isolated endothelial cells from 2K and 2K-1C rat aortas by flow-cytometry using NO selective fluorescent probe, DAF-2DA. The sGC activity/expression was also evaluated. PE-induced contractile response is lower in 2K-1C than in 2K intact-endothelium rat aorta. This is due to higher eNOS Ser(1177) phosphorylation in 2K-1C, which induces the eNOS overactivation. It was abolished by NOS or sGC inhibition. Phenylephrine reduces NO production in 2K as compared to the basal level, but it is not modified in 2K-1C. In PE-stimulated endothelial cells, the NO production is higher in 2K-1C than in 2K. Phenylephrine induces higher cGMP production in 2K-1C than in 2K, despite the lower expression of sGC in 2K-1C. Our results suggest that alpha1-adrenoceptor activation contributes to the increased activity of the enzyme eNOS by Ser(1177) phosphorylation in 2K-1C intact-endothelium aorta, which consequently decreases PE-induced contractile response.

  16. 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

  17. Adenosine A2B receptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells

    PubMed Central

    Du, Xiaolong; Ou, Xuehai; Song, Tao; Zhang, Wentao; Cong, Fei; Zhang, Shihui

    2015-01-01

    Angiogenesis is critical to wound repair due to its role in providing oxygen and nutrients that are required to support the growth and function of reparative cells in damaged tissues. Adenosine receptors are claimed to be of paramount importance in driving wound angiogenesis by inducing VEGF. However, the underlying mechanisms for the regulation of adenosine receptors in VEGF as well as eNOS remain poorly understood. In the present study, we found that adenosine and the non-selective adenosine receptor agonists (NECA) induced tube formation in HMEC-1 in a dose-dependent manner. Adenosine or NECA (10 µmol/L) significantly augmented the number and length of the segments in comparison with the control. Simultaneously, VEGF and eNOS were significantly upregulated following the administration of 10 µmol/L NECA, while they were suppressed after A2B AR genetic silencing and pharmacological inhibition by MRS1754. In addition, VEGF expression and eNOS bioavailability elimination significantly reduced the formation of capillary-like structures. Furthermore, the activation of A2B AR by NECA significantly increased the intracellular cAMP levels and concomitant CREB phosphorylation, eventually leading to the production of VEGF in HMEC-1. However, the activated PKA-CREB pathway seemed to be invalidated in the induction of eNOS. Moreover, we found that the elicited PI3K/AKT signaling in response to the induction of NECA assisted in regulating eNOS but failed to impact on VEGF generation. In conclusion, the A2B AR activation-driven angiogenesis via cAMP-PKA-CREB mediated VEGF production and PI3K/AKT-dependent upregulation of eNOS in HMEC-1. PMID:25966978

  18. Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

    SciTech Connect

    Nagy, Edit; Caidahl, Kenneth; Franco-Cereceda, Anders; Baeck, Magnus

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. Black-Right-Pointing-Pointer We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. Black-Right-Pointing-Pointer Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. Black-Right-Pointing-Pointer The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. Black-Right-Pointing-Pointer Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C{sub 4} (LTC{sub 4}) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = -0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = -0.498; P = 0.0298) only in tricuspid aortic valves

  19. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase

    PubMed Central

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  20. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase.

    PubMed

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  1. Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications.

    PubMed

    Miao, Xiao Niu; Siu, Kin Lung; Cai, Hua

    2015-10-01

    Rupture of abdominal aortic aneurysm (AAA) is a lethal event. No oral medicine has been available to prevent or treat AAA. We have recently identified a novel mechanism of eNOS uncoupling by which AAA develops, in angiotensin II (Ang II) infused hyperphenylalaninemia 1 (hph-1) mice. Using this unique model we investigated effects on AAA formation of the L-type calcium channel blocker nifedipine, in view of the unclear relationship between hypertension and AAA, and unclear mechanisms of aneurysm protective effects of some blood pressure lowering drugs. Six-month old hph-1 mice were infused with Ang II (0.7 mg/kg/day) for 2 weeks, and fed nifedipine chow at two different doses (5 and 20 mg/kg/day). While the high dose of nifedipine reduced blood pressure, the lower dose had no effect. Interestingly, the incidence rate of AAA dropped from 71% to 7 and 12.5% for low and high dose nifedipine, respectively. Expansion of abdominal aorta, determined by ultrasound imaging, was abolished by both doses of nifedipine, which recoupled eNOS completely to improve NO bioavailability. Both also abrogated aortic superoxide production. Of note, Ang II activation of NADPH oxidase in vascular smooth muscle cells and endothelial cells, known to uncouple eNOS, was also attenuated by nifedipine. Although low dose was a sub-pressor while the high dose reduced blood pressure via inhibition of calcium channels, both doses were highly effective in preventing AAA by preserving eNOS coupling activity to eliminate sustained oxidative stress from uncoupled eNOS. These data demonstrate that oral treatment of nifedipine is highly effective in preserving eNOS function to attenuate AAA formation. Nifedipine may be used for AAA prevention either at low dose in AAA risk group, or at high dose in patients with co-existing hypertension. PMID:26254182

  2. Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

    PubMed Central

    Cooper, Leroy L.; Mitchell, Gary F.

    2016-01-01

    Background Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. Summary Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery. Aortic stiffening thereby impairs a protective mechanism that shields the peripheral microcirculation from excessive pulsatility within downstream target organs. Beyond midlife, aortic stiffness increases rapidly and exposes the cerebral microcirculation to abnormal pulsatile mechanical forces that are associated with microvascular damage and remodeling in the brain. Aortic stiffening and high-flow pulsatility are associated with alterations in the microvasculature of the brain; however, a mechanistic link between aortic stiffness and memory has not been established. We showed that in a community-based sample of older individuals, cerebrovascular resistance and white matter hyperintensities - markers of cerebrovascular remodeling and damage - mediated the relation between higher aortic stiffness and lower performance on memory function tests. These data suggest that microvascular and white matter damage associated with excessive aortic stiffness contribute to impaired memory function with advancing age. Key Messages Increasing evidence suggests that vascular etiologies - including aortic stiffness and microvascular damage - contribute to memory impairment and the pathogenesis of dementia, including Alzheimer's disease. Interventions that reduce aortic stiffness may delay memory decline among older individuals. PMID:27752478

  3. Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

    SciTech Connect

    Knuckles, Travis L.; Lund, Amie K.; Lucas, Selita N.; Campen, Matthew J.

    2008-08-01

    Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 {mu}g/m{sup 3} for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS.

  4. ENO2 activity is required for the development and reproductive success of plants, and is feedback-repressed by AtMBP-1.

    PubMed

    Eremina, Marina; Rozhon, Wilfried; Yang, Saiqi; Poppenberger, Brigitte

    2015-03-01

    Enolases are key glycolytic enzymes that are highly conserved in prokaryotic and eukaryotic organisms, and are among the most abundant cytosolic proteins. In this study we provide evidence that activity of the enolase ENO2 is essential for the growth and development of plants. We show that Arabidopsis plants with compromised ENO2 function, which were generated by mutating the LOS2/ENO2 locus, have severe cellular defects, including reduced cell size and defective cell differentiation with restricted lignification. At the tissue and organ level LOS2/ENO2-deficient plants are characterized by the reduced growth of shoots and roots, altered vascular development and defective secondary growth of stems, impaired floral organogenesis and defective male gametophyte function, resulting in embryo lethality as well as delayed senescence. These phenotypes correlate with reduced lignin and increased salicylic acid contents as well as altered fatty acid and soluble sugar composition. In addition to an enolase the LOS2/ENO2 locus encodes the transcription factor AtMBP-1, and here we reveal that this bifunctionality serves to maintain the homeostasis of ENO2 activity. In summary, we show that in plants enolase function is required for the formation of chorismate-dependent secondary metabolites, and that this activity is feedback-inhibited by AtMBP-1 to enable the normal development and reproductive success of plants.

  5. Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture.

    PubMed

    Xiao, Yangming; Liu, Qin; Han, Hai-Chao

    2016-09-01

    Artery buckling alters the fluid shear stress and wall stress in the artery but its temporal effect on vascular wall remodeling is poorly understood. The purpose of this study was to investigate the early effect of artery buckling on endothelial nitric oxide synthase (eNOS) expression and extracellular matrix remodeling. Bilateral porcine carotid arteries were maintained in an ex vivo organ culture system with and without buckling while under the same physiological pressure and flow rate for 3-7 days. Matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin, elastin, collagen I, III and IV, tissue inhibitor of metalloproteinase-2 (TIMP-2), and eNOS were determined using Western blotting and immunohistochemistry. Our results showed that MMP-2 expression level was significantly higher in buckled arteries than in the controls and higher at the inner curve than at the outer curve of buckled arteries, while collagen IV content showed an opposite trend, suggesting that artery buckling increased MMP-2 expression and collagen IV degradation in a site-specific fashion. However, no differences for MMP-9, fibronectin, elastin, collagen I, III, and TIMP-2 were observed among the outer and inner curve sides of buckled arteries and straight controls. Additionally, eNOS expression was significantly decreased in buckled arteries. These results suggest that artery buckling triggers uneven wall remodeling that could lead to development of tortuous arteries. PMID:26913855

  6. Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system.

    PubMed

    Akasaki, Takashi; Ohya, Yusuke; Kuroda, Junya; Eto, Kimika; Abe, Isao; Sumimoto, Hideki; Iida, Mitsuo

    2006-10-01

    Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension. PMID:17283869

  7. Fo Shou San, an Ancient Chinese Herbal Decoction, Protects Endothelial Function through Increasing Endothelial Nitric Oxide Synthase Activity

    PubMed Central

    Bi, Cathy W. C.; Xu, Li; Tian, Xiao Yu; Liu, Jian; Zheng, Ken Y. Z.; Lau, Chi Wai; Lau, David T. W.; Choi, Roy C. Y.; Dong, Tina T. X.; Huang, Yu; Tsim, Karl W. K.

    2012-01-01

    Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2∶3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca2+ levels in HUVECs, and the Ca2+ chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca2+ and a reduction of ROS. PMID:23284736

  8. From Unicuspid to Quadricuspid: Influence of Aortic Valve Morphology on Aortic 3D Hemodynamics

    PubMed Central

    Entezari, Pegah; Schnell, Susanne; Mahadevia, Riti; Malaisrie, Chris; McCarthy, Patrick; Mendelson, Marla; Collins, Jeremy; Carr, James C.; Markl, Michael; Barker, Alex J.

    2016-01-01

    Purpose To assess the impact of aortic valve morphology on aortic hemodynamicsbetweennormal tricuspid and congenitally anomalous aortic valvesranging from unicuspid to quadricuspid morphology. Materials and Methods Aortic 3D blood flow was evaluated by 4D flow MRI in 14 healthy volunteers with normal trileaflet valves and 14 patients withunicuspid(n=3), bicuspid (n=9, 3 ‘true’ bicuspid, 3 right-left (RL), 3 right-non (RN) coronary leaflet fusion, and quadricuspid aortic valves (n=2). Data analysis included the co-registered visualization of aortic valve morphology with systolic 3D blood flow. The influence of valve morphology on aortic hemodynamics was quantified by valve flow angle. Results All RL-BAV were associated with flow jets directed towards the right anterior aortic wallwhile RN-fusion and unicuspid valves resulted in flow jet patterns towards the right-posterior or posterior wall. Flow angles were clearly influenced by valve morphology(47°±10, 28°±2, 29°±18, 18°±12, 15°±2 for unicuspid, trueBAV, RN-BAV, RL-BAV, quadricuspid valves) and increased compared to controls (7.2°±1.1, p=0.001). Conclusions Altered 3D aortic hemodynamics are impacted by the morphology of congenitally malformed aortic valves. PMID:24265266

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

    PubMed

    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

  10. 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

  11. Exercise training in athletes with bicuspid aortic valve does not result in increased dimensions and impaired performance of the left ventricle.

    PubMed

    Stefani, Laura; Galanti, Giorgio; Innocenti, Gabriele; Mercuri, Roberto; Maffulli, Nicola

    2014-01-01

    Background. Bicuspid aortic valve (BAV) is one of the most common congenital heart disease (0.9%-2%) and is frequently found in the athletes and in the general population. BAV can lead to aortic valve dysfunction and to a progressive aortic dilatation. Trained BAV athletes exhibit a progressive enlargement of the left ventricle (LV) compared to athletes with normal aortic valve morphology. The present study investigates the possible relationship between different aortic valve morphology and LV dimensions. Methods. In the period from 2000 to 2011, we investigated a total of 292 BAV subjects, divided into three different groups (210 athletes, 59 sedentaries, and 23 ex-athletes). A 2D echocardiogram exam to classify BAV morphology and measure the standard LV systo-diastolic parameters was performed. The study was conducted as a 5-year follow-up echocardiographic longitudinal and as cross-sectional study. Results. Typical BAV was more frequent in all three groups (68% athletes, 67% sedentaries, and 63% ex-athletes) than atypical. In BAV athletes, the typical form was found in 51% (107/210) of soccer players, 10% (21/210) of basketball players, 10% track and field athletics (20/210), 8% (17/210) of cyclists, 6% (13/210) swimmers, and 15% (32/210) of rugby players and others sport. Despite a progressive enlargement of the LV (P < 0.001) observed during the follow-up study, no statistical differences of the LV morphology and function were evident among the diverse BAV patterns either in sedentary subjects or in athletes. Conclusion. In a large population of trained BAV athletes, with different prevalence of typical and atypical BAV type, there is a progressive nonstatistically significant enlargement of the LV. In any case, the dimensions of the LV remained within normal range. The metabolic requirements of the diverse sport examined in the present investigations do not seem to produce any negative impact in BAV athletes.

  12. Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta

    PubMed Central

    Silva, Josiane F.; Correa, Izabella C.; Diniz, Thiago F.; Lima, Paulo M.; Santos, Roger L.; Cortes, Steyner F.; Coimbra, Cândido C.; Lemos, Virginia S.

    2016-01-01

    Background: The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process. Methods: High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown. Results: Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS−/− animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet–fed animals

  13. Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta

    PubMed Central

    Silva, Josiane F.; Correa, Izabella C.; Diniz, Thiago F.; Lima, Paulo M.; Santos, Roger L.; Cortes, Steyner F.; Coimbra, Cândido C.; Lemos, Virginia S.

    2016-01-01

    Background: The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process. Methods: High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown. Results: Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS−/− animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet–fed animals

  14. Balloon aortic valvuloplasty.

    PubMed

    Wang, A; Harrison, J K; Bashore, T M

    1997-01-01

    Balloon aortic valvuloplasty is a percutaneous, therapeutic option for patients with severe aortic stenosis, yet the effectiveness of this procedure is dependent on the morphology of the stenotic aortic valve and the respective mechanism of dilation. In younger patients with congenital aortic stenosis, acute and intermediate-term results are good. However, in adult patients, in whom degenerative aortic stenosis is the most common cause, the acute clinical and hemodynamic benefits of balloon aortic valvuloplasty are not lasting, as restenosis occurs in most patients within 6 months. Sympatomatic relief for adults undergoing balloon aortic valvuloplasty is only apparent in patients with normal left ventricular function, who generally are also candidates for aortic valve replacement. Furthermore, the long-term survival for adults after balloon aortic valvuloplasty is similar to the natural history of untreated severe aortic stenosis. In this article, the mechanism of balloon aortic valvuloplasty, as well as its clinical and hemodynamic effects, are reviewed in the context of the different morphological types of aortic stenosis. In addition, two large registries of adult patients treated with balloon aortic valvuloplasty provide important information regarding the acute and long-term results of this procedure and are reviewed.

  15. Aortic Annular Enlargement during Aortic Valve Replacement

    PubMed Central

    Dumani, Selman; Likaj, Ermal; Dibra, Laureta; Llazo, Stavri; Refatllari, Ali

    2016-01-01

    In the surgery of aortic valve replacement is always attempted, as much as possible, to implant the larger prosthesis with the mains goals to enhance the potential benefits, to minimise transvalvular gradient, decrease left ventricular size and avoid the phenomenon of patient-prosthesis mismatch. Implantation of an ideal prosthesis often it is not possible, due to a small aortic annulus. A variety of aortic annulus enlargement techniques is reported to avoid patient-prosthesis mismatch. We present the case that has submitted four three times open heart surgery. We used Manouguian technique to enlarge aortic anulus with excellent results during the fourth time of surgery. PMID:27703574

  16. Multi-dimensional ENO schemes for general geometries

    NASA Technical Reports Server (NTRS)

    Harten, Ami; Chakravarthy, Sukumar R.

    1991-01-01

    A class of ENO schemes is presented for the numerical solution of multidimensional hyperbolic systems of conservation laws in structured and unstructured grids. This is a class of shock-capturing schemes which are designed to compute cell-averages to high order accuracy. The ENO scheme is composed of a piecewise-polynomial reconstruction of the solution form its given cell-averages, approximate evolution of the resulting initial value problem, and averaging of this approximate solution over each cell. The reconstruction algorithm is based on an adaptive selection of stencil for each cell so as to avoid spurious oscillations near discontinuities while achieving high order of accuracy away from them.

  17. Abdominal Aortic Aneurysms: Treatments

    MedlinePlus

    ... information Membership Directory (SIR login) Interventional Radiology Abdominal Aortic Aneurysms Interventional Radiologists Treat Abdominal Aneurysms Nonsurgically Interventional radiologists ...

  18. Resistance exercise training increase activation of AKT-eNOS and Ref-1 expression by FOXO-1 activation in aorta of F344 rats

    PubMed Central

    Li, Meng; Li, Wei; Yoon, Jin-Hwan; Jeon, Byeong Hwa; Lee, Sang Ki

    2015-01-01

    Purpose This study investigated the effects of resistance exercise on the Akt-eNOS, the activation of antioxidant protein and FOXO1 in the aorta of F344 rats. Methods Male 7 week-old F344 rats were randomly divided into 2 groups: a climbing group (n = 6) and a sedentary group (n = 6). H&E staining and western blotting were used to analyze the rat aortas and target proteins. Results Resistance exercise training did not significantly affect aortic structure. Phosphorylation of AKT and eNOS and expression of MnSOD and Ref-1 were significantly increased while FOXO1 phosphorylation was significantly decreased in the resistance exercise group compared with the sedentary group. Conclusion We demonstrate that resistance exercise activates the Akt-eNOS and Ref-1 protein without changes to aortic thickness via FOXO-1 activation in the aorta of F344 rats. PMID:26526775

  19. Comparative immunoprophylactic efficacy of Haemonchus contortus recombinant enolase (rHcENO) and Con A purified native glycoproteins in sheep.

    PubMed

    Kalyanasundaram, Aravindan; Jawahar, Shabnam; Ilangopathy, Manikkavasagan; Palavesam, Azahahianambi; Raman, Muthusamy

    2015-07-01

    Haemonchus contortus is the most economically important blood feeding nematode parasite of sheep and goats all over the world. Enolase in helminth parasites is a multi-functional enzyme which involves in glycolysis and host tissue invasion. In this study, the recombinant H. contortus enolase (rHcENO) was evaluated for its immunoprophylactic efficacy in sheep along with Con A purified native glycoproteins in a vaccine challenge trial. Group I and Group II experimental sheep were immunized thrice with rHcENO and Con A purified native glycoproteins along with Montanide ISA 61 VG adjuvant. The animals were challenged with 5000 L3 stage active H. contortus larvae after 21 days of third immunization. A significant increase in the IgG titre was observed in rHcENO and Con A purified native glycoproteins immunized animals as compared to the control animals. Immunoprotective efficacy of Con A purified native glycoproteins was comparatively higher than rHcENO antigen.

  20. Triterpenoic Acids from Apple Pomace Enhance the Activity of the Endothelial Nitric Oxide Synthase (eNOS).

    PubMed

    Waldbauer, Katharina; Seiringer, Günter; Nguyen, Dieu Linh; Winkler, Johannes; Blaschke, Michael; McKinnon, Ruxandra; Urban, Ernst; Ladurner, Angela; Dirsch, Verena M; Zehl, Martin; Kopp, Brigitte

    2016-01-13

    Pomace is an easy-accessible raw material for the isolation of fruit-derived compounds. Fruit consumption is associated with health-promoting effects, such as the prevention of cardiovascular disease. Increased vascular nitric oxide (NO) bioavailability, for example, due to an enhanced endothelial nitric oxide synthase (eNOS) activity, could be one molecular mechanism mediating this effect. To identify compounds from apple (Malus domestica Borkh.) pomace that have the potential to amplify NO bioavailability via eNOS activation, a bioassay-guided fractionation of the methanol/water (70:30) extract has been performed using the (14)C-L-arginine to (14)C-L-citrulline conversion assay (ACCA) in the human endothelium-derived cell line EA.hy926. Phytochemical characterization of the active fractions was performed using the spectrophotometric assessment of the total phenolic content, as well as TLC, HPLC-DAD-ELSD, and HPLC-MS analyses. Eleven triterpenoic acids, of which one is a newly discovered compound, were identified as the main constituents in the most active fraction, accompanied by only minor contents of phenolic compounds. When tested individually, none of the tested compounds exhibited significant eNOS activation. Nevertheless, cell stimulation with the reconstituted compound mixture restored eNOS activation, validating the potential of apple pomace as a source of bioactive components.

  1. Association of eNOS gene polymorphisms with essential hypertension in the Han population in southwestern China.

    PubMed

    Li, J; Cun, Y; Tang, W R; Wang, Y; Li, S N; Ouyang, H R; Wu, Y R; Yu, H J; Xiao, C J

    2011-01-01

    Endothelial nitric oxide synthase (eNOS) plays an important role in maintaining blood pressure homeostasis and vascular integrity. Polymorphisms in the eNOS gene have been found to be associated with hypertension in different human populations, including Northern and Southern Chinese Han populations. To examine the relationship of three eNOS gene polymorphisms, T-786C (rs2070744), G894T (rs1799983), and G10T (rs7830), with hypertension in the Han population in southwestern China, we carried out a study of the genotypes of three SNPs in 510 hypertensive and 510 normotensive subjects from the Yunnan Province by using PCR-RFLP and sequencing. Our SNP analyses showed that the distribution of the T-786C polymorphism did not differ between patients and controls, and that G894T and G10T are significantly associated with hypertension in females, adjusted for covariates. Compared with the other haplotypes, haplotype H1 (TGG), carrying protective 10G and 894G alleles, significantly decreased the risk of increased essential hypertension in females, with an odds ratio of 0.68 (P = 10(-5)). These results suggest that the eNOS polymorphism is one of the factors contributing to the predisposition for essential hypertension in the Han population in southwestern China. PMID:21968727

  2. Increased serum IgG4 levels and intimal IgG4-positive cell infiltration in rapidly growing aortic aneurysm

    PubMed Central

    Fujita, Shuichi; Nishioka, Nobu; Ito, Takahide; Wada, Yuki; Kakita, Ken; Ozawa, Hideki; Tsuji, Motomu; Katsumata, Takahiro

    2013-01-01

    A 67-year-old Japanese man had been complaining of discomfort in the chest and back and feeling febrile for 2 weeks. Chest computed tomography indicated a thoracic aortic aneurysm. He occasionally showed a high fever (up to 38.0°C), even after hospital admission, irrespective of antibiotic therapy. The patient was found to have elevated serum IgG4 levels (366 mg/dL). The aneurysm demonstrated rapid growth; therefore, rifampicin-soaked woven Dacron synthetic graft replacement was performed 22 days after admission. Immunohistostatining of the resected aorta segment showed an IgG4-positive plasma cell infiltrate within the intimal layer neighboring the cholesterol-rich atheromatous plaque. After surgery, the patient’s serum IgG4 level dropped acutely; however, it did not reach the normal range. The possible role of IgG4 in the development or suppression of aortic remodeling, as well as in atherogenesis, among patients with rapidly growing aortic aneurysm requires further investigation. PMID:27489625

  3. Vasoinhibins Prevent Bradykinin-Stimulated Endothelial Cell Proliferation by Inactivating eNOS via Reduction of both Intracellular Ca2+ Levels and eNOS Phosphorylation at Ser1179

    PubMed Central

    Thebault, Stéphanie; González, Carmen; García, Celina; Zamarripa, David Arredondo; Nava, Gabriel; Vaca, Luis; López-Casillas, Fernando; de la Escalera, Gonzalo Martínez; Clapp, Carmen

    2011-01-01

    Vasoinhibins, a family of antiangiogenic peptides derived from prolactin proteolysis, inhibit the vascular effects of several proangiogenic factors, including bradykinin (BK). Here, we report that vasoinhibins block the BK-induced proliferation of bovine umbilical vein endothelial cells. This effect is mediated by the inactivation of endothelial nitric oxide synthase (eNOS), as the NO donor DETA-NONOate reverted vasoinhibin action. It is an experimentally proven fact that the elevation of intracellular Ca2+ levels ([Ca2+]i) upon BK stimulation activates eNOS, and vasoinhibins blocked the BK-mediated activation of phospholipase C and the formation of inositol 1,4,5-triphosphate leading to a reduced release of Ca2+ from intracellular stores. The [Ca2+]i rise evoked by BK also involves the influx of extracellular Ca2+ via canonical transient receptor potential (TRPC) channels. Vasoinhibins likely interfere with TRPC-mediated Ca2+ entry since La3+, which is an enhancer of TRPC4 and TRPC5 channel activity, prevented vasoinhibins from blocking the stimulation by BK of endothelial cell NO production and proliferation, and vasoinhibins reduced the BK-induced increase of TRPC5 mRNA expression. Finally, vasoinhibins prevented the BK-induced phosphorylation of eNOS at Ser1179, a post-translational modification that facilitates Ca2+-calmodulin activation of eNOS. Together, our data show that vasoinhibins, by lowering NO production through the inhibition of both [Ca2+]i mobilization and eNOS phosphorylation, prevent the BK-induced stimulation of endothelial cell proliferation. Thus, vasoinhibins help to regulate BK effects on angiogenesis and vascular homeostasis.

  4. Effect of Exercise Training on Enos Expression, NO Production and Oxygen Metabolism in Human Placenta

    PubMed Central

    Ramírez-Vélez, Robinson; Bustamante, Juanita; Czerniczyniec, Analia; Aguilar de Plata, Ana C.; Lores-Arnaiz, Silvia

    2013-01-01

    Objective To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS), nitric oxide (NO) production and oxygen metabolism in human placenta. Methods The study included 20 nulliparous in gestational week 16–20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10) took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55–75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each) using barbells (1–3 kg/exercise) and low-to-medium resistance bands. The control group (n = 10) undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. Results Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05). Conclusion Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of

  5. Endovascular Repair of Thoracic Aortic Aneurysms

    PubMed Central

    Findeiss, Laura K.; Cody, Michael E.

    2011-01-01

    Degenerative aneurysms of the thoracic aorta are increasing in prevalence; open repair of descending thoracic aortic aneurysms is associated with high rates of morbidity and mortality. Repair of isolated descending thoracic aortic aneurysms using stent grafts was introduced in 1995, and in an anatomically suitable subgroup of patients with thoracic aortic aneurysm, repair with endovascular stent graft provides favorable outcomes, with decreased perioperative morbidity and mortality relative to open repair. The cornerstones of successful thoracic endovascular aneurysm repair are appropriate patient selection, thorough preprocedural planning, and cautious procedural execution, the elements of which are discussed here. PMID:22379281

  6. Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS

    PubMed Central

    Song, Kai; Shang, Zheng-Jun

    2013-01-01

    Hypoxia, ephrin-A1 and endothelial nitric oxide synthase (eNOS) have been proved to play critical roles in tumor angiogenesis. However, how ephrin-A1 is regulated by hypoxia and whether ephrin-A1 cooperates with eNOS in modulation of angiogenesis remain to be addressed in details. Here we demonstrated that both ephrin-A1 in squamous cell carcinoma cells (SCC-9) and especially soluble ephrin-A1 in the supernatants were up-regulated under hypoxic condition. An increased nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was observed in ephrin-A1-induced angiogenesis which was reversed after co-culture with eNOS specific inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Western blot analysis confirmed that both phosphorylation of AktSer473 and eNOSSer1177 were up-regulated in ephrin-A1-stimulated HUVECs, with the total eNOS expression unchanged. The specific inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002, significantly down-regulated ephrin-A1-induced expression of phosphorylated AktSer473 as well as phosphorylation of eNOSSer1177. These results revealed a possible novel mechanism whereby ephrin-A1 is regulated in tumor microenvironment and promotes angiogenesis through a coordinated cross-talk with PI3K/Akt-dependent eNOS activation which may relate to normal vascular development and tumor neovascularization. PMID:24040255

  7. Acute aortic syndrome

    PubMed Central

    2016-01-01

    Acute aortic syndrome (AAS) is a term used to describe a constellation of life-threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another. PMID:27386405

  8. Para-aortic lymphocyst.

    PubMed

    Helmkamp, B F; Krebs, H B; Isikoff, M B; Poliakoff, S R; Averette, H E

    1980-10-15

    Although numerous articles regarding the etiology, incidence, complications, and management of pelvic lymphocysts have been published in the American literature since 1958, there has been no mention of para-aortic lymphocyst as a complication of para-aortic node dissection. Two recent cases of symptomatic para-aortic lymphocyst have prompted a review of our para-aortic node dissection technique when this procedure is not combined with a more extensive pelvic lymphadenectomy. Our modification in technique is to use retroperitoneal para-aortic drainage by constant pressure-controlled suction following closure of the posterior parietal peritoneum, and the results in our first 15 patients are presented. There were no complications related to the drainage technique. Abdominal ultrasound and intravenous urography have proved to be excellent diagnostic tools in the initial evaluation and subsequent follow-up of para-aortic lymphocytes.

  9. Acute aortic syndrome.

    PubMed

    Corvera, Joel S

    2016-05-01

    Acute aortic syndrome (AAS) is a term used to describe a constellation of life-threatening aortic diseases that have similar presentation, but appear to have distinct demographic, clinical, pathological and survival characteristics. Many believe that the three major entities that comprise AAS: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU), make up a spectrum of aortic disease in which one entity may evolve into or coexist with another. Much of the confusion in accurately classifying an AAS is that they present with similar symptoms: typically acute onset of severe chest or back pain, and may have similar radiographic features, since the disease entities all involve injury or disruption of the medial layer of the aortic wall. The accurate diagnosis of an AAS is often made at operation. This manuscript will attempt to clarify the similarities and differences between AD, IMH and PAU of the ascending aorta and describe the challenges in distinguishing them from one another. PMID:27386405

  10. Combined surgical and catheter-based treatment of extensive thoracic aortic aneurysm and aortic valve stenosis.

    PubMed

    De Backer, Ole; Lönn, Lars; Søndergaard, Lars

    2015-02-15

    An extensive thoracic aortic aneurysm (TAA) is a potentially life-threatening condition and remains a technical challenge to surgeons. Over the past decade, repair of aortic arch aneurysms has been accomplished using both hybrid (open and endovascular) and totally endovascular techniques. Thoracic endovascular aneurysm repair (TEVAR) has changed and extended management options in thoracic aorta disease, including in those patients deemed unfit or unsuitable for open surgery. Accordingly, transcatheter aortic valve replacement (TAVR) is increasingly used to treat patients with symptomatic severe aortic valve stenosis (AS) who are considered at high risk for surgical aortic valve replacement. In this report, we describe the combined surgical and catheter-based treatment of an extensive TAA and AS. To our knowledge, this is the first report of hybrid TAA repair combined with TAVR.

  11. The many faces of aortic dissections: Beware of unusual presentations.

    PubMed

    Scaglione, Mariano; Salvolini, Luca; Casciani, Emanuele; Giovagnoni, Andrea; Mazzei, Maria Antonietta; Volterrani, Luca

    2008-03-01

    Aortic dissection is gaining recognition in Western societies, and it is being diagnosed with increasing frequency. New diagnostic imaging modalities, longer life expectancy, as well as the increase in the number patients suffering from hypertension have all contributed to the growing awareness of aortic dissection. Nevertheless, as many as 30% of patients ultimately diagnosed with acute dissection are first thought to be suffering from something else. The increased availability and use of multidetector computed tomography has led to the incidental discovery of aortic dissection in very different settings. This article focuses on unusual presentations of painless aortic dissection. It is important for radiologists to remember that aortic dissections may present in different ways, not only as an acute, critical fatality but also with subtle, unusual signs and symptoms, which apparently do not seem to be strictly related to aortic diseases. PMID:17950552

  12. Aortic Wall Injury Related to Endovascular Therapy for Aortic Coarctation.

    PubMed

    Tretter, Justin T; Jones, Thomas K; McElhinney, Doff B

    2015-09-01

    Aortic wall complications can occur in unrepaired aortic coarctation (CoA) and after surgical repair or endovascular treatment. This review summarizes the available literature and current understanding of aortic wall injury (AWI) surrounding the management of CoA, focusing specifically on acute and follow-up AWI after endovascular treatment. There have been 23 reported cases of aortic rupture after endovascular treatment for CoA, including angioplasty alone, bare metal stenting, and primary covered stent therapy. Even if these published cases represent only a minority of ruptures that have actually occurred, the incidence is substantially <1%. The incidence of acute aneurysm formation was 0% to 13% after angioplasty, 0% to 5% after bare metal stent placement, and <1% after covered stent placement. The reported incidence and natural history of both acute and new AWI during follow-up after endovascular therapy for CoA varies considerably, likely secondary to ascertainment and reporting biases and inconsistent definitions. Although important AWI after endovascular treatment of CoA seems to be declining in frequency with increasing experience and improving technology, it remains one of the most important potential adverse outcomes. Long-term surveillance for new AWI and monitoring of existing AWI is mandatory, with institution of appropriate treatment when necessary. A central research focus in this population should be determination of the appropriate treatment for both native and recurrent CoA across various ages with regard to limiting recurrent CoA and preventing associated aortic wall complications, in addition to determining the appropriate treatment of various AWI. Consistent definitions and reporting are necessary to truly understand the incidence of, risk factors for, and measures protective against AWI after angioplasty or stent implantation for CoA.

  13. Two functionally distinct pools of eNOS in endothelium are facilitated by myoendothelial junction lipid composition.

    PubMed

    Biwer, Lauren A; Taddeo, Evan P; Kenwood, Brandon M; Hoehn, Kyle L; Straub, Adam C; Isakson, Brant E

    2016-07-01

    In resistance arteries, endothelial cells (EC) make contact with smooth muscle cells (SMC), forming myoendothelial junctions (MEJ). Endothelial nitric oxide synthase (eNOS) is present in the luminal side of the EC (apical EC) and the basal side of the EC (MEJ). To test if these eNOS pools acted in sync or separately, we co-cultured ECs and SMCs, then stimulated SMCs with phenylephrine (PE). Adrenergic activation causes inositol [1,4,5] triphosphate (IP3) to move from SMC to EC through gap junctions at the MEJ. PE increases MEJ eNOS phosphorylation (eNOS-P) at S1177, but not in EC. Conversely, we used bradykinin (BK) to increase EC calcium; this increased EC eNOS-P but did not affect MEJ eNOS-P. Inhibiting gap junctions abrogated the MEJ eNOS-P after PE, but had no effect on BK eNOS-P. Differential lipid composition between apical EC and MEJ may account for the compartmentalized eNOS-P response. Indeed, DAG and phosphatidylserine are both enriched in MEJ. These lipids are cofactors for PKC activity, which was significantly increased at the MEJ after PE. Because PKC activity also relies on endoplasmic reticulum (ER) calcium release, we used thapsigargin and xestospongin C, BAPTA, and PKC inhibitors, which caused significant decreases in MEJ eNOS-P after PE. Functionally, BK inhibited leukocyte adhesion and PE caused an increase in SMC cGMP. We hypothesize that local lipid composition of the MEJ primes PKC and eNOS-P for stimulation by PE, allowing for compartmentalized function of eNOS in the blood vessel wall. PMID:27106139

  14. Abdominal Aortic Aneurysmectomy in Renal Transplant Patients

    PubMed Central

    Jebara, Victor A.; Fabiani, Jean-Noël; Moulonguet-Deloris, L.; Acar, Christophe; Debauchez, Mathieu; Chachques, J.C.; Glotz, Denis; Duboust, Alain; Langanay, Thierry; Carpentier, Alain

    1990-01-01

    Because renal transplantation is allowing an increased number of patients to survive for prolonged periods, abdominal aortic aneurysms can be expected to occur with growing frequency in these patients. Surgical management of such cases involves the provision of allograft protection. To date, the literature contains 15 reports of abdominal aortic aneurysms in renal allograft recipients. We describe a 16th case and discuss the management of these patients. (Texas Heart Institute Journal 1990;17:240-4) Images PMID:15227179

  15. A family of high-order targeted ENO schemes for compressible-fluid simulations

    NASA Astrophysics Data System (ADS)

    Fu, Lin; Hu, Xiangyu Y.; Adams, Nikolaus A.

    2016-01-01

    Although classical WENO schemes have achieved great success and are widely accepted, they exhibit several shortcomings. They are too dissipative for direct simulations of turbulence and lack robustness when very-high-order versions are applied to complex flows. In this paper, we propose a family of high-order targeted ENO schemes which are applicable for compressible-fluid simulations involving a wide range of flow scales. In order to increase the numerical robustness as compared to very-high-order classical WENO schemes, the reconstruction dynamically assembles a set of low-order candidate stencils with incrementally increasing width. While discontinuities and small-scale fluctuations are efficiently separated, the numerical dissipation is significantly diminished by an ENO-like stencil selection, which either applies a candidate stencil with its original linear weight, or removes its contribution when it is crossed by a discontinuity. The background linear scheme is optimized under the constraint of preserving an approximate dispersion-dissipation relation. By means of quasi-linear analyses and practical numerical experiments, a set of case-independent parameters is determined. The general formulation of arbitrarily high-order schemes is presented in a straightforward way. A variety of benchmark-test problems, including broadband waves, strong shock and contact discontinuities are studied. Compared to well-established classical WENO schemes, the present schemes exhibit significantly improved robustness, low numerical dissipation and sharp discontinuity capturing. They are particularly suitable for DNS and LES of shock-turbulence interactions.

  16. Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications.

    PubMed

    ALrefai, Abeer A; Habib, Mona Salah El-Din; Yaseen, Rehab I; Gabr, Mahmoud K; Habeeb, Rabab M

    2016-10-01

    This study evaluated the association of NOS3 polymorphisms with hypertension risk and complications. eNOS (G894T) SNP was performed by RT-PCR on 70 hypertensive patients (25 were hypertensive, 25 were hypertensive with CAD, and 20 were diabetic with hypertension) and 30 age- and gender-matched individuals. Lipid and glucose profile were assessed by standard colorimetric assay. Our results revealed that combination of (GT + TT) genotype and T allele significantly increases the risk of hypertension (OR = 3.86 and 4.33), respectively. Subgroup analysis showed significant association between CAD with eNOS (G894T) mutant genotype (P = 0.002) and allele frequency (P < 0.001). Moreover, the mutant homozygous and heterozygous eNOS genotype together were significantly associated with higher TC, LDLc, (P < 0.001), and TG (P = 0.001). Thus, hypercholesterolemia (P < 0.001 and OR = 12.48) increases the risk of hypertension among T carrier. These results indicated that the T carriers significantly increase hypertension risk and complication (CAD), mainly with hypercholesterolemia and in elderly. PMID:27557897

  17. Physical exercise, aortic blood pressure, and aortic wall elasticity and composition in rats.

    PubMed

    Niederhoffer, N; Kieffer, P; Desplanches, D; Lartaud-Idjouadiene, I; Sornay, M H; Atkinson, J

    2000-04-01

    With a training schedule (8 weeks' treadmill running at 30 m/min up a 10% incline 5 d/wk for 90 min/day), we investigated whether exercise modifies aortic wall dimensions, composition (calcium and elastin content), or stiffness in normotensive 6-month-old male Wistar WAG/Rij rats. Maximal oxygen uptake was measured in half of the rats (n=10 per group). Wall stiffness was evaluated in the other half (9 trained and 10 untrained) on the basis of changes in thoracoabdominal pressure pulse wave velocity and differences in amplitude between the peripheral and central aortic pressure signals. Experiments were performed in nonanesthetized, unrestrained rats and then after pithing. The impact of exercise on the oxidative capacity of the plantaris muscles was evaluated with the measurement of citrate synthase activity. Training increased maximal oxygen uptake by 34% and citrate synthase activity by 40%. Mean peripheral aortic pressure increased by 6% and 19% in trained rats, under awake and pithed conditions, whereas mean central aortic pressure increased by 16%, after pithing only. All indexes of aortic stiffness were similar in trained and control rats, as were aortic wall dimensions, composition, cardiac mass, and heart rate. In conclusion, physical exercise in young rats appears to have no effect on aortic stiffness. PMID:10775562

  18. Nanobacteria-associated calcific aortic valve stenosis.

    PubMed

    Jelic, Tomislav M; Chang, Ho-Huang; Roque, Rod; Malas, Amer M; Warren, Stafford G; Sommer, Andrei P

    2007-01-01

    Calcific aortic valve stenosis is the most common valvular disease in developed countries, and the major reason for operative valve replacement. In the US, the current annual cost of this surgery is approximately 1 billion dollars. Despite increasing morbidity and mortality, little is known of the cellular basis of the calcifications, which occur in high-perfusion zones of the heart. The case is presented of a patient with calcific aortic valve stenosis and colonies of progressively mineralized nanobacteria in the fibrocalcific nodules of the aortic cusps, as revealed by transmission electron microscopy. Consistent with their outstanding bioadhesivity, nanobacteria might serve as causative agents in the development of calcific aortic valve stenosis. PMID:17315391

  19. Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria-style diet

    PubMed Central

    López-Canales, Jorge Skiold; Lozano-Cuenca, Jair; López-Canales, Oscar Alberto; Aguilar-Carrasco, José Carlos; Aranda-Zepeda, Lidia; López-Sánchez, Pedro; Castillo-Henkel, Enrique Fernando; López-Mayorga, Ruth Mery; Valencia-Hernández, Ignacio

    2015-01-01

    The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10−9–10−5-mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10−5-mol/L NG-nitro-l-arginine methyl ester, 10−2-mol/L tetraethylammonium, 10−3-mol/L 4-aminopyridine, 10−7-mol/L apamin plus 10−7-mol/L charybdotoxin, 10−5-mol/L indomethacin, or 10−5-mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca2+-activated and voltage-activated K+ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect. PMID:25881486

  20. Living Water. Eno River State Park: An Environmental Education Learning Experience Designed for the Middle Grades.

    ERIC Educational Resources Information Center

    Hartley, Scott; Woods, Martha

    This learning packet, one in a series of eight, was developed by the Eno River State Park in North Carolina for Grades 5-6 to teach about various aspects of water life on the Eno River. Loose-leaf pages are presented in nine sections that contain: (1) introductions to the North Carolina State Park System, the Eno River State Park, and to the…

  1. 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

  2. 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.

  3. Small aortic valve annulus in children with fixed subaortic stenosis.

    PubMed

    Thilenius, O G; Campbell, D; Bharati, S; Lev, M; Arcilla, R A

    1989-01-01

    Twenty-one hearts with fixed subaortic stenosis (FSAS) were examined pathologically. Thirty children with no hemodynamically significant heart disease, 31 children with valvar aortic stenosis, and 25 children with FSAS were studied by echo- and angiocardiography. The following conclusions were drawn: (1) Patients with FSAS often have abnormal aortic valve leaflets as well as small aortic valve annulus. (2) A small aortic annulus/descending aorta ratio is probably present at birth, and may decrease with increasing age. (3) In some patients with FSAS the aortic valve annulus is too small for simple resection of the fibroelastic tissue. A Konno operation is needed for these patients. (4) M-mode echocardiography has not been useful in identifying abnormally small aortic valve annulus in FSAS patients.

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

    PubMed

    Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong; Park, Young Mi; Kang, Duk-Hee; Jo, Inho

    2013-07-12

    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 and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser(1179)) in a time-dependent manner (up to 40min 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(2+) levels. Treatment with KN-93, a selective inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser(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(1179) phosphorylation. This study suggests that FIR radiation increases NO production via increasing CaMKII-mediated eNOS-Ser(1179) phosphorylation but TRPV channels may not be involved in this pathway. Our results may provide the molecular mechanism by which FIR radiation improves endothelial function.

  5. 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

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

    PubMed Central

    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

    2014-01-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca2+-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. PMID:25015964

  7. Intra-aortic balloon pump associated with dynamic left ventricular outflow tract obstruction after valve replacement for aortic stenosis.

    PubMed

    Morewood, G H; Weiss, S J

    2000-03-01

    An unstable patient with critical aortic stenosis had an intra-aortic balloon pump placed preoperatively for hemodynamic support and alleviation of symptoms. After separation from cardiopulmonary bypass following aortic valve replacement, the patient was hypotensive with increased pulmonary artery pressures. Transesophageal echocardiography revealed left ventricular outflow tract obstruction associated with systolic anterior motion of the mitral valve and severe mitral regurgitation. This pathophysiology was present when ventricular systole was preceded by balloon counterpulsation, but was absent during unassisted systole. This case report demonstrates a potentially significant untoward effect of intra-aortic balloon pump augmentation after aortic valve replacement for aortic stenosis. The timely diagnosis of this iatrogenic condition in the operating room permitted the prompt implementation of appropriate management strategies and avoided unnecessary surgical intervention.

  8. RNase G-dependent degradation of the eno mRNA encoding a glycolysis enzyme enolase in Escherichia coli.

    PubMed

    Kaga, Naoko; Umitsuki, Genryou; Nagai, Kazuo; Wachi, Masaaki

    2002-10-01

    Escherichia coli RNase G, encoded by the rng gene, is involved in the processing of 16S rRNA and degradation of the adhE mRNA encoding a fermentative alcohol dehydrogenase. In a search for the intracellular target RNAs of RNase G other than the 16S rRNA precursor and adhE mRNA, total cellular proteins from rng+ and rng::cat cells were compared by two-dimensional gel electrophoresis. The amount of enolase encoded by the eno gene reproducibly increased two- to three-fold in the rng::cat mutant strain compared with the rng+ parent strain. Rifampicin chase experiments showed that the half-life of the eno mRNA was some 3 times longer in the rng::cat mutant than in the wild type. These results indicate that the eno mRNA was a substrate of RNase G in vivo, in addition to 16S rRNA precursor and adhE mRNA. PMID:12450135

  9. A three-dimensional co-culture model of the aortic valve using magnetic levitation.

    PubMed

    Tseng, Hubert; Balaoing, Liezl R; Grigoryan, Bagrat; Raphael, Robert M; Killian, T C; Souza, Glauco R; Grande-Allen, K Jane

    2014-01-01

    The aortic valve consists of valvular interstitial cells (VICs) and endothelial cells (VECs). While these cells are understood to work synergistically to maintain leaflet structure and valvular function, few co-culture models of these cell types exist. In this study, aortic valve co-cultures (AVCCs) were assembled using magnetic levitation and cultured for 3 days. Immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction were used to assess the maintenance of cellular phenotype and function, and the formation of extracellular matrix. AVCCs stained positive for CD31 and α-smooth muscle actin (αSMA), demonstrating that the phenotype was maintained. Functional markers endothelial nitric oxide synthase (eNOS), von Willebrand factor (VWF) and prolyl-4-hydroxylase were present. Extracellular matrix components collagen type I, laminin and fibronectin also stained positive, with reduced gene expression of these proteins in three dimensions compared to two dimensions. Genes for collagen type I, lysyl oxidase and αSMA were expressed less in AVCCs than in 2-D cultures, indicating that VICs are quiescent. Co-localization of CD31 and αSMA in the AVCCs suggests that endothelial-mesenchymal transdifferentiation might be occurring. Differences in VWF and eNOS in VECs cultured in two and three dimensions also suggests that the AVCCs possibly have anti-thrombotic potential. Overall, a co-culture model of the aortic valve was designed, and serves as a basis for future experiments to understand heart valve biology. PMID:24036238

  10. Abdominal aortic aneurysm.

    PubMed

    Keisler, Brian; Carter, Chuck

    2015-04-15

    Abdominal aortic aneurysm refers to abdominal aortic dilation of 3.0 cm or greater. The main risk factors are age older than 65 years, male sex, and smoking history. Other risk factors include a family history of abdominal aortic aneurysm, coronary artery disease, hypertension, peripheral artery disease, and previous myocardial infarction. Diagnosis may be made by physical examination, an incidental finding on imaging, or ultrasonography. The U.S. Preventive Services Task Force released updated recommendations for abdominal aortic aneurysm screening in 2014. Men 65 to 75 years of age with a history of smoking should undergo one-time screening with ultrasonography based on evidence that screening will improve abdominal aortic aneurysm-related mortality in this population. Men in this age group without a history of smoking may benefit if they have other risk factors (e.g., family history of abdominal aortic aneurysm, other vascular aneurysms, coronary artery disease). There is inconclusive evidence to recommend screening for abdominal aortic aneurysm in women 65 to 75 years of age with a smoking history. Women without a smoking history should not undergo screening because the harms likely outweigh the benefits. Persons who have a stable abdominal aortic aneurysm should undergo regular surveillance or operative intervention depending on aneurysm size. Surgical intervention by open or endovascular repair is the primary option and is typically reserved for aneurysms 5.5 cm in diameter or greater. There are limited options for medical treatment beyond risk factor modification. Ruptured abdominal aortic aneurysm is a medical emergency presenting with hypotension, shooting abdominal or back pain, and a pulsatile abdominal mass. It is associated with high prehospitalization mortality. Emergent surgical intervention is indicated for a rupture but has a high operative mortality rate. PMID:25884861

  11. Predicting long-term outcomes of acute aortic dissection: a focus on gender.

    PubMed

    Divchev, Dimitar; Najjar, Tarek; Tillwich, Falko; Rehders, Tim; Palisch, Holger; Nienaber, Christoph A

    2015-03-01

    Acute aortic disease ranks as the 19th leading cause of death with steadily increasing incidence. The prevalence of aneurysms varies depending on the localization along the aorta with a mortality of aortic rupture of around 80%. Traditionally, aortic disease affects men more frequently than women, however, with a varying gender ratio. Nevertheless, in the setting of acute aortic dissection, the International Registry of Acute Aortic Dissections identified significant gender-related differences in the management of both sexes with acute aortic conditions. Current data suggest that women are at an increased risk of both dying from aortic dissection and having aorta-related complications than men. This review aims to report on current evidence of gender impact on natural history, treatment and outcomes in patients with acute aortic dissection. PMID:25608580

  12. Aortic valve replacement with sutureless and rapid deployment aortic valve prostheses.

    PubMed

    Berretta, Paolo; Di Eusanio, Marco

    2016-09-01

    Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement (AVR) interventions has increased with outcomes that have been improved despite increasing age of patients and increasing burden of comorbidities. However, despite such excellent results and its well-established position, conventional AVR has undergone great development over the previous two decades. Such progress, by way of less invasive incisions and use of new technologies, including transcatheter aortic valve implantation and sutureless valve prostheses, is intended to reduce the traumatic impact of the surgical procedure, thus fulfilling lower risk patients' expectations on the one hand, and extending the operability toward increasingly high-risk patients on the other. Sutureless and rapid deployment aortic valves are biological, pericardial prostheses that anchor within the aortic annulus with no more than three sutures. The sutureless prostheses, by avoiding the passage and the tying of the sutures, significantly reduce operative times and may improve outcomes. However, there is still a paucity of robust, evidence-based data on the role and performance of sutureless AVR. Therefore, strongest long-term data, randomized studies and registry data are required to adequately assess the durability and long-term outcomes of sutureless aortic valve replacement. PMID:27582765

  13. Aortic valve replacement with sutureless and rapid deployment aortic valve prostheses

    PubMed Central

    Berretta, Paolo; Di Eusanio, Marco

    2016-01-01

    Aortic valve stenosis is the most common valve disease in the western world. Over the past few years the number of aortic valve replacement (AVR) interventions has increased with outcomes that have been improved despite increasing age of patients and increasing burden of comorbidities. However, despite such excellent results and its well-established position, conventional AVR has undergone great development over the previous two decades. Such progress, by way of less invasive incisions and use of new technologies, including transcatheter aortic valve implantation and sutureless valve prostheses, is intended to reduce the traumatic impact of the surgical procedure, thus fulfilling lower risk patients' expectations on the one hand, and extending the operability toward increasingly high-risk patients on the other. Sutureless and rapid deployment aortic valves are biological, pericardial prostheses that anchor within the aortic annulus with no more than three sutures. The sutureless prostheses, by avoiding the passage and the tying of the sutures, significantly reduce operative times and may improve outcomes. However, there is still a paucity of robust, evidence-based data on the role and performance of sutureless AVR. Therefore, strongest long-term data, randomized studies and registry data are required to adequately assess the durability and long-term outcomes of sutureless aortic valve replacement. PMID:27582765

  14. Transcatheter aortic valve implantation.

    PubMed

    Kapadia, Samir R; Tuzcu, E Murat

    2009-12-01

    Aortic stenosis is the most important valvular heart disease affecting the elderly population. Surgical aortic valve replacement is the mainstay of treatment, although a substantial number of patients are considered high risk for surgery. Many of these patients do not undergo surgery and have poor outcomes from medically treated symptomatic, severe aortic stenosis. Transcatheter aortic valve implantation (TAVI) provides a promising treatment option for some of these patients. Several devices are under investigation. The Edwards Sapien valve (Edwards Lifesciences, Irvine, CA) and the CoreValve (Medtronic, Minneapolis, MN) have the largest human experience to date. Initial data suggest that these devices have an acceptable safety profile and provide excellent hemodynamic relief of aortic stenosis. The Edwards Sapien valve is currently under investigation in the United States in the PARTNER (Placement of Aortic Transcatheter Valve) trial in high-risk surgical or inoperable patients; TAVI is available for clinical use in both Canada and Europe. TAVI is not used in low- or intermediate-risk surgical patients; however, future studies may prove its applicability in these subsets. The major complications of TAVI include access site-related problems and device malpositioning/migration. There are several new-generation prosthetic valves and delivery systems designed to be low profile and repositionable. Technical advances and refinement of the implantation methods may make TAVI even safer and ultimately a better treatment option, not only for patients with high surgical risk but also for those with moderate or low risk.

  15. [Inflammatory abdominal aortic aneurysm].

    PubMed

    Ziaja, K; Sedlak, L; Urbanek, T; Kostyra, J; Ludyga, T

    2000-01-01

    The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.

  16. Enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

    PubMed Central

    Mutze, Kathrin; Vierkotten, Sarah; Milosevic, Jadranka; Eickelberg, Oliver; Königshoff, Melanie

    2015-01-01

    ABSTRACT The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI) and type II (ATII) cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2) and an increase in enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker), exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC), whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair. PMID:26035385

  17. eNOS gene deletion restores blood-brain barrier integrity and attenuates neurodegeneration in the thiamine-deficient mouse brain.

    PubMed

    Beauchesne, Elizabeth; Desjardins, Paul; Hazell, Alan S; Butterworth, Roger F

    2009-10-01

    Wernicke's encephalopathy is a cerebral disorder caused by thiamine (vitamin B(1)) deficiency (TD). Neuropathologic consequences of TD include region-selective neuronal cell loss and blood-brain barrier (BBB) breakdown. Early increased expression of the endothelial isoform of nitric oxide synthase (eNOS) occurs selectively in vulnerable brain regions in TD. We hypothesize that region-selective eNOS induction in TD leads to altered expression of tight junction proteins and BBB breakdown. In order to address this issue, TD was induced in C57BL/6 wild-type (WT) and eNOS(-/-) mice by feeding a thiamine-deficient diet and treatment with the thiamine antagonist pyrithiamine. Pair-fed control mice were fed the same diet with additional thiamine. In medial thalamus of TD-WT mice (vulnerable area), increased heme oxygenase-1 and S-nitrosocysteine immunostaining was observed in vessel walls, compared to pair-fed control-WT mice. Concomitant increases in IgG extravasation, decreases in expression of the tight junction proteins occludin, zona occludens-1 and zona occludens-2, and up-regulation of matrix metalloproteinase-9 in endothelial cells were observed in the medial thalamus of TD-WT mice. eNOS gene deletion restored these BBB alterations, suggesting that eNOS-derived nitric oxide is a major factor leading to cerebrovascular alterations in TD. However, eNOS gene deletion only partially attenuated TD-related neuronal cell loss, suggesting the presence of mechanisms additional to BBB disruption in the pathogenesis of these changes.

  18. The role of balloon aortic valvuloplasty in the era of transcatheter aortic valve implantation.

    PubMed

    Wacławski, Jacek; Wilczek, Krzysztof; Pres, Damian; Krajewski, Adam; Poloński, Lech; Zembala, Marian; Gąsior, Mariusz

    2015-03-01

    Balloon aortic valvuloplasty is recommended in patients not suitable for transcatheter aortic valve implantation/aortic valve replacement (TAVI/AVR) or when such interventions are temporarily contraindicated. The number of performed balloon aortic valvuloplasty (BAV) procedures has been increasing in recent years. Valvuloplasty enables the selection of individuals with severe left ventricular dysfunction or with symptoms of uncertain origin resulting from concomitant disorders (including chronic obstructive pulmonary disease [COPD]) who can benefit from destination therapy (AVR/TAVI). Thanks to improved equipment, the number of adverse effects is now lower than it was in the first years after the advent of BAV. Valvuloplasty can be safely performed even in unstable patients, but long-term results remain poor. In view of the limited availability of TAVI in Poland, it is reasonable to qualify patients for BAV more often, as it is a relatively safe procedure improving the clinical condition of patients awaiting AVR/TAVI. PMID:26336471

  19. Endovascular Management of Chronic Type B Dissecting Aortic Aneurysm Utilizing Aortic and Renal Stents

    SciTech Connect

    Taylor, J. D. Dunckley, M.; Thompson, M.; Morgan, R. A.

    2008-07-15

    Over the last 10 years endovascular stent-graft placement has been increasingly used to treat complicated acute Type B thoracic aortic dissections. While studies have demonstrated the use of additional aortic stent-grafts to treat continued false lumen perfusion and case reports have detailed the use of renal artery stents to treat renal ischemia related to aortic dissection, to our knowledge the adjuvant use of renal artery stents to reduce false lumen perfusion has not been reported. We present the case of a 72-year-old male who had previously undergone endovascular repair of a complicated Type B thoracic aortic dissection and presented with an expanding false lumen in the peridiaphragmatic aorta despite coverage of the entire thoracic aorta. This was treated by closure of a right renal fenestration using a renal stent.

  20. 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

  1. Comparison of Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement to Improve Quality of Life in Patients >70 Years of Age with Severe Aortic Stenosis

    PubMed Central

    Kocaaslan, Cemal; Ketenci, Bülend; Yılmaz, Mehmet; Kehlibar, Tamer; Memetoğlu, Mehmet Erdem; Ertaş, Gökhan; Eren, Mehmet; Demirtaş, Mahmut Murat

    2016-01-01

    Objective: Transcatheter aortic valve implantation has recently been used in the treatment of severe aortic valve stenosis, particularly in patients with high mortality and morbidity rates for open surgery. The purpose of this study was to compare quality of life in patients over 70 years of age undergoing surgical or transcatheter aortic valve implantation, before the procedure and in the early post-procedural period. Methods: Seventy-nine patients were included in the study, 38 (48.1%) male and 41 (51.9%) female. Mean age of patients was 74.3±5.2 (70-91) years. The surgical aortic valve replacement group consisted of 51 (64.6%) patients and the transcatheter aortic valve replacement group of 28 (35.4%). Quality of life data before the procedure and at the 3rd month postoperatively in patients aged 70 years and older undergoing surgical or transcatheter aortic valve implantation were assessed using the 36-item Short Form Health Survey form. Results: Positive increases in physical task difficulty (13.2±9.8 vs. 5.1±7.3) (P=0.001), emotional task difficulty (14.4±11.9 vs. 8.5±6.4) (P=0.035), and mental health (0.4±10.4 vs. 9.6±15.1) (P=0.001; P<0.01) scores in patients undergoing transcatheter aortic valve replacement were significantly higher compared to the surgical aortic valve replacement group. No statistically significant difference was determined between the groups in terms of pain, vitality, social function, physical function or general health scores in the preoperative and postoperative periods. Conclusion: The positive increase in quality of life parameters in the transcatheter aortic valve implantation group at the 3rd month postoperatively was significantly higher compared to the surgical aortic valve replacement group. PMID:27074268

  2. Differential Activation of Multiple Signaling Pathways Dictates eNOS Upregulation by FGF2 but not VEGF in Placental Artery Endothelial Cells1

    PubMed Central

    Mata-Greenwood, Eugenia; Liao, Wu-Xiang; Zheng, Jing; Chen, Dong-Bao

    2008-01-01

    Fibroblast growth factor (FGF2), but not vascular endothelial growth factor (VEGF), upregulates endothelial nitric oxide synthase (eNOS) protein expression, at least in part, via activation of extracellular signal-regulated kinase 2/1 (ERK2/1) in ovine fetoplacental artery endothelial (oFPAE) cells. Herein we further investigated the temporal effects of FGF2 and VEGF on other signaling pathways including members (Jun N-terminal kinase JNK1/2 and p38MAPK) of mitogen-activated protein kinases (MAPK), phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene homolog 1 (PI3K/AKT1), and the tyrosine kinase c-SRC, and examined if either one or more of these pathways play a role in the differential regulation of eNOS by FGF2 and VEGF. We first confirmed that in oFPAE cells, FGF2, but not VEGF, increased eNOS protein. FGF2 stimulated eNOS protein in a time and concentration dependent manner, which also depended on cell density. FGF2 provoked sustained (5 min to 12 h) whereas VEGF only stimulated transient (5 min) ERK2/1 phosphorylation. FGF2 was 1.7-fold more potent in stimulating ERK2/1 phosphorylation than VEGF. FGF2 and VEGF only transiently activated JNK1/2 and AKT1 within 5 min; however, FGF2 was a stronger stimulus than VEGF. FGF2 and VEGF did not significantly activate p38MAPK at 5 min; however, VEGF stimulated p38MAPK phosphorylation at 60 min. VEGF but not FGF2 significantly stimulated c-SRC phosphorylation. Inhibitors of MEK-ERK2/1 (PD98059), JNK1/2 (SP600125) and PI3K (wortmannin), but not p38MAPK (SB203580) and SRC (PP2), decreased the FGF2-increased eNOS protein expression. Thus, the FGF2-induced eNOS protein expression requires activation of multiple signaling pathways including ERK2/1, JNK1/2 and PI3K/AKT1. Differences in intensity and temporal patterns of activation of these pathways by FGF2 and VEGF may account for their differential effects on eNOS expression in OFPAE cells. PMID:18571718

  3. Echocardiographic assessment of severity of aortic regurgitation.

    PubMed Central

    Gray, K E; Barritt, D W

    1975-01-01

    An echocardiographic study of left ventricular diameter was made in 27 patients with aortic regurgitation. Comparison was made with a group of 21 normal subjects and a group of 6 patients with large left ventricles without valvar regurgitation. Total stroke volume, total left ventricular output, and ejection fraction were derived by the method of cubing the left ventricular diameter to give approximate left ventricular volumes at and-diastole and end-systole. The patients were assessed independently and placed into three grades of severity. The eechocardiographic dimensions of patients with mild aortic regurgitation were not significantly different from those of the normal subjects. With increasing severity of aortic regurgitation, there were increases in group values for left ventricular diameter, total stroke volume, and total left ventricular output. The ejection fraction was depressed below the normal range in only one patient with aortic regurgitation. It is concluded that echocardiographic measurement of left ventribular dimensions is of value in assessing the severity of aortic regurgitation. Images PMID:1156476

  4. Transcatheter aortic valve implantation: current trends and future directions.

    PubMed

    Allahwala, Usaid K; Hansen, Peter S; Danson, Edward J; Straiton, Nicola; Sinhal, Ajay; Walters, Darren L; Bhindi, Ravinay

    2016-01-01

    Transcatheter aortic valve implantation (TAVI) has been increasingly utilized for the treatment of severe symptomatic aortic stenosis in inoperable and high surgical risk patients. Recent advances in valve technology include repositionable scaffolds and smaller delivery systems, as well as improvement in periprocedural imaging. These advances have resulted in reduction of vascular complications, rates of paravalvular aortic regurgitation and periprocedural stroke and improved overall outcomes. Increasingly, TAVI is the preferred treatment for high-risk surgical patients with severe aortic stenosis. Consequently, there is growing interest for the use of TAVI in lower surgical risk patients. Furthermore, the role of TAVI has expanded to include valve-in-valve procedures for the treatment of degenerative bioprosthetic valves and bicuspid aortic valves. Questions remain in regard to the optimal management of concurrent coronary artery disease, strategies to minimize valve leaflet restriction and treatment of conduction abnormalities as well as identifying newer indications for its use.

  5. Surgical Aortic Valvuloplasty Versus Balloon Aortic Valve Dilatation in Children.

    PubMed

    Donald, Julia S; Konstantinov, Igor E

    2016-09-01

    Balloon aortic valve dilatation (BAD : is assumed to provide the same outcomes as surgical aortic valvuloplasty (SAV). However, the development of precise modern surgical valvuloplasty techniques may result in better long-term durability of the aortic valve repair. This review of the recent literature suggests that current SAV provides a safe and durable repair. Furthermore, primary SAV appears to have greater freedom from reintervention and aortic valve replacement when compared to BAD. PMID:27587493

  6. Hybrid Endovascular Repair in Aortic Arch Pathologies: A Retrospective Study

    PubMed Central

    Ma, Xiaohui; Guo, Wei; Liu, Xiaoping; Yin, Tai; Jia, Xin; Xiong, Jiang; Zhang, Hongpeng; Wang, Lijun

    2010-01-01

    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. PMID:21151464

  7. Screening for Abdominal Aortic Aneurysm

    MedlinePlus

    Understanding Task Force Recommendations Screening for Abdominal Aortic Aneurysm The U.S. Preventive Services Task Force (Task Force) ... final recommendation statement on Screening for Abdominal Aortic Aneurysm. This final recommendation statement applies to adults ages ...

  8. Inflammatory Characteristics of Stenotic Aortic Valves: A Comparison between Rheumatic and Nonrheumatic Aortic Stenosis.

    PubMed

    Wallby, Lars; Steffensen, Thora; Jonasson, Lena; Broqvist, Mats

    2013-01-01

    Background. Although our comprehension of nonrheumatic aortic stenosis (NRAS) has increased substantially during the last decade, less is known about the histopathology of rheumatic aortic stenosis (RAS). The aim of this study was to investigate rheumatic aortic stenosis by means of analyses previously used in nonrheumatic stenosis. Material and Methods. Valve specimens were obtained from 39 patients referred to hospital due to significant aortic stenosis. According to established macroscopic criteria the valves were divided into two groups consisting of 29 NRAS and 10 RAS valves. Mononuclear inflammatory cells and apolipoproteins were investigated using immunohistochemical analyses. Results. The localisation of calcification differed in tricuspid nonrheumatic valves when compared to bicuspid nonrheumatic and rheumatic valves. The RAS valves revealed a lower degree of T lymphocyte infiltration compared with the NRAS valves. Infiltration of macrophages was seen in all valves and there were no differences regarding deposition of apolipoprotein. Conclusion. Rheumatic and nonrheumatic aortic stenotic valves show a similar and significant chronic inflammation. The similarities regarding the localisation of calcification indicate that the valve anomaly/morphology can influence the pathogenesis of aortic stenosis. Finally, our findings highlight the question of a postinflammatory valvular disease of other causes than rheumatic fever.

  9. 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.

  10. Aneurysms: thoracic aortic aneurysms.

    PubMed

    Chun, Kevin C; Lee, Eugene S

    2015-04-01

    Thoracic aortic aneurysms (TAAs) have many possible etiologies, including congenital heart defects (eg, bicuspid aortic valves, coarctation of the aorta), inherited connective tissue disorders (eg, Marfan, Ehlers-Danlos, Loeys-Dietz syndromes), and degenerative conditions (eg, medial necrosis, atherosclerosis of the aortic wall). Symptoms of rupture include a severe tearing pain in the chest, back, or neck, sometimes associated with cardiovascular collapse. Before rupture, TAAs may exert pressure on other thoracic structures, leading to a variety of symptoms. However, most TAAs are asymptomatic and are found incidentally during imaging for other conditions. Diagnosis is confirmed with computed tomography scan or echocardiography. Asymptomatic TAAs should be monitored with imaging at specified intervals and patients referred for repair if the TAAs are enlarging rapidly (greater than 0.5 cm in diameter over 6 months for heritable etiologies; greater than 0.5 cm over 1 year for degenerative etiologies) or reach a critical aortic diameter threshold for elective surgery (5.5 cm for TAAs due to degenerative etiologies, 5.0 cm when associated with inherited syndromes). Open surgery is used most often to treat asymptomatic TAAs in the ascending aorta and aortic arch. Asymptomatic TAAs in the descending aorta often are treated medically with aggressive blood pressure control, though recent data suggest that endovascular procedures may result in better long-term survival rates. PMID:25860136

  11. Quadricuspid aortic valves.

    PubMed

    Timperley, Jonathan; Milner, Robert; Marshall, Andrew J; Gilbert, Timothy J

    2002-12-01

    Quadricuspid aortic valves (QAV) are a rare but well recognized cause of significant aortic regurgitation. The first case was found reported in 1862. Since then there have been 110 reported cases of QAV and we report 4 more. Previously, these were diagnosed at the time of surgery or postmortem examination. With advances in echocardiography, including harmonic imaging, and also the advent of transesophageal echocardiography, more cases are being diagnosed prior to surgery. We describe four more cases, three diagnosed preoperatively and one at the time of surgery, and then review the previously reported cases. Of the 114 cases reported, 46 had the aortic valve replaced, most commonly in the 5th and 6th decade of life. Hurwitz and Roberts classified quadricuspid valves according to the size of the leaflets. It has previously been believed that QAVs with four equal sized leaflets were less likely to develop significant aortic regurgitation; however, on review of the available cases, this would not appear to be the case. The preoperative diagnosis of QAVs is important as they can be associated with abnormally placed coronary ostium. Of the 114 cases reported, there are 10 reports of abnormally placed ostia. There has been at least one reported case of death occurring because of obstruction of an abnormally placed right coronary ostium by a prosthetic aortic valve.

  12. Awake transapical aortic valve implantation.

    PubMed

    Petridis, Francesco Dimitri; Savini, Carlo; Castelli, Andrea; Di Bartolomeo, Roberto

    2012-05-01

    Transapical aortic valve implantation is being employed as a less invasive alternative to open heart surgery in high-risk patients with severe aortic stenosis. Here we report the case of an awake transapical aortic valve implantation in a patient with severe chronic obstructive pulmonary disease.

  13. Premature aortic stiffness in systemic lupus erythematosus by transesophageal echocardiography.

    PubMed

    Roldan, C A; Joson, J; Qualls, C R; Sharrar, J; Sibbitt, W L

    2010-12-01

    To assess aortic stiffness by transesophageal echocardiography (TEE) and to determine its clinical predictors and relation to age, blood pressure, renal function, and atherosclerosis, 50 patients with systemic lupus erythematosus (SLE), 94% women, with a mean age of 38 ± 12 years, and 22 age and gender-matched healthy controls underwent clinical and laboratory evaluations and multiplane TEE to assess stiffness, intima-media thickness (IMT), and plaques of the proximal, mid, and distal descending thoracic aorta. Stiffness at each level and overall aortic stiffness by the pressure-strain elastic modulus was higher in patients than in controls after adjusting for age (overall, 8.25 ± 4.13 versus 6.1 ± 2.5 Pascal units, p = 0.01). Patients had higher aortic stiffness than controls after adjusting both groups to the same mean age, blood pressure, creatinine, and aortic IMT (p = 0.005). Neither IMT nor plaques were predictors of aortic stiffness. Moreover, normotensive patients, those without aortic plaques, and non-smokers had higher stiffness than controls (all p < 0.05). Age at SLE diagnosis and non-neurologic damage score were the only SLE-specific independent predictors of aortic stiffness (both p ≤ 0.01). Thus, increased aortic stiffness is an early manifestation of lupus vasculopathy that seems to precede the development of hypertension and atherosclerosis.

  14. Abdominal aortic aneurysmectomy in renal transplant patients.

    PubMed Central

    Lacombe, M

    1986-01-01

    Five patients who had undergone renal transplantation 3 months to 23 years ago were operated on successfully for an abdominal aortic aneurysm. In the first case, dating from 1973, the kidney was protected by general hypothermia. In the remaining patients, no measure was used to protect the kidney. Only one patient showed a moderate increase of blood creatinine in the postoperative period; renal function returned to normal in 15 days. All five patients have normal renal function 6 months to 11 years after aortic repair. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided adequate surgical technique is used. Such a technique is described in detail. Its use simplifies surgical treatment of such lesions and avoids the complex procedures employed in the seven previously published cases. Images FIGS. 1A and B. FIGS. 2A and B. FIGS. 3A and B. FIGS. 4A and B. FIGS. 5A and B. PMID:3510592

  15. Endovascular repair of thoracic aortic aneurysm

    PubMed Central

    Akin, Ibrahim; Kische, Stephan; Rehders, Tim C.; Nienaber, Christoph A.; Rauchhaus, Mathias

    2010-01-01

    A thoracic aortic aneurysm (TAA) is a potentially life-threatening condition with structural weakness of the aortic wall, which can progress to arterial dilatation and rupture. Today, both an increasing awareness of vascular disease and the access to tomographic imaging facilitate the diagnosis of TAA even in an asymptomatic stage. The risk of rupture for untreated aneurysms beyond a diameter of 5.6 cm ranges from 46% to 74% and the two-year mortality rate is greater than 70%, with most deaths resulting from rupture. Treatment options include surgical and non-surgical repair to prevent aneurysm enlargement and rupture. While most cases of ascending aortic involvement are subject to surgical repair (partially with valve-preserving techniques), aneurysm of the distal arch and descending thoracic aorta are amenable to emerging endovascular techniques as an alternative to classic open repair or to a hybrid approach (combining debranching surgery with stent grafting) in an attempt to improve outcomes. PMID:22419919

  16. Proximal aortic dissection (dissecting aortic aneurysm) in a mature ostrich.

    PubMed

    Ferreras, M C; González, J; Pérez, V; Reyes, L E; Gómez, N; Pérez, C; Corpa, J M; García-Marín, J F

    2001-01-01

    The gross and histopathologic lesions observed in a case of spontaneous proximal aortic dissection (dissecting aortic aneurysm) in a mature ostrich are reported. At necropsy, a dissecting intramural hematoma was seen in the proximal aorta, extended about 12 cm distally from the aortic valves. Histopathologic changes in aortic dissection included fragmentation and disruption of elastic laminae, presence of cystic extracellular spaces, and pooling of ground substance in the tunica media. Hepatic copper levels were measured, and the low concentration found suggested that a copper deficiency together with other risk factors such as the elevation of blood pressure may have been implicated in the development of the aortic dissection seen in this ostrich.

  17. Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies.

    PubMed

    da Guarda, Caroline C; Santiago, Rayra P; Pitanga, Thassila N; Santana, Sanzio S; Zanette, Dalila L; Borges, Valéria M; Goncalves, Marilda S

    2016-07-01

    The sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p<0.01), while treatment with HU and simvastatin reduced the production (p<0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p<0.01). Heme increased eNOS production, (p<0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p<0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p<0.001) and was reduced by treatment with HU (p<0.001), ascorbic acid (p<0.001) and simvastatin (p<0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients.

  18. Transcatheter Aortic Valve Implantation.

    PubMed

    Malaisrie, S Chris; Iddriss, Adam; Flaherty, James D; Churyla, Andrei

    2016-05-01

    Severe aortic stenosis (AS) is a life-threatening condition when left untreated. Aortic valve replacement (AVR) is the gold standard treatment for the majority of patients; however, transcatheter aortic valve implantation/replacement (TAVI/TAVR) has emerged as the preferred treatment for high-risk or inoperable patients. The concept of transcatheter heart valves originated in the 1960s and has evolved into the current Edwards Sapien and Medtronic CoreValve platforms available for clinical use. Complications following TAVI, including cerebrovascular events, perivalvular regurgitation, vascular injury, and heart block have decreased with experience and evolving technology, such that ongoing trials studying TAVI in lower risk patients have become tenable. The multidisciplinary team involving the cardiac surgeon and cardiologist plays an essential role in patient selection, procedural conduct, and perioperative care.

  19. Critical Transitions in Early Embryonic Aortic Arch Patterning and Hemodynamics

    PubMed Central

    Kowalski, William J.; Dur, Onur; Wang, Yajuan; Patrick, Michael J.; Tinney, Joseph P.; Keller, Bradley B.; Pekkan, Kerem

    2013-01-01

    Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a

  20. Aortic Input Impedance during Nitroprusside Infusion

    PubMed Central

    Pepine, Carl J.; Nichols, W. W.; Curry, R. C.; Conti, C. Richard

    1979-01-01

    Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through “impedance” reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m2 and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 μg/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 μg/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 μg/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction. PMID:457874

  1. Aortic stiffness and distensibility among hypertensives.

    PubMed

    Meenakshisundaram, R; Kamaraj, K; Murugan, S; Thirumalaikolundusubramanian, P

    2009-09-01

    significant. Aortic stiffness was greater in hypertensives and it was independent of gender, but increased with duration of hypertension. Hypertension has effects on the aorta (decreased aortic distensibility and increased aortic stiffness) and left ventricle (increased left ventricular mass and left ventricular hypertrophy). These changes can be identified and monitored while the patient is on antihypertensive therapy along with life-style modifications, as these are reversible. Nevertheless, these aspects do not receive due attention in medical education and training on hypertension.

  2. Endovascular aortic aneurysm operations.

    PubMed

    Najibi, Sasan; Terramani, Thomas T; Weiss, Victor J; Smith, Robert B; Salam, Atef A; Dodson, Thomas F; Chaikof, Elliot L; Lumsden, Alan B

    2002-02-01

    Options for the treatment of abdominal and thoracic aortic aneurysms are in a state of evolutionary change. The development and continued refinement of the endoluminal approaches has decreased the need for open aortic aneurysm surgery. Endovascular stent graft technology is an area of active research in which both the delivery systems and the endografts are undergoing continued improvement so that patients with what was previously thought to be unfavorable anatomy may be treated by these means. The design and deployment techniques of the currently available endografts, as well as those in clinical trials, are presented. PMID:11822962

  3. Sodium nitrite exerts an antihypertensive effect and improves endothelial function through activation of eNOS in the SHR.

    PubMed

    Ling, Wei Chih; Murugan, Dharmani Devi; Lau, Yeh Siang; Vanhoutte, Paul M; Mustafa, Mohd Rais

    2016-01-01

    Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS. PMID:27616322

  4. Sodium nitrite exerts an antihypertensive effect and improves endothelial function through activation of eNOS in the SHR

    PubMed Central

    Ling, Wei Chih; Murugan, Dharmani Devi; Lau, Yeh Siang; Vanhoutte, Paul M.; Mustafa, Mohd Rais

    2016-01-01

    Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L−1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS. PMID:27616322

  5. Aortic wraps a modification to aortic grafting.

    PubMed

    Gordon, J A

    1989-09-01

    Aortic wrapping has been attempted on occasion when the standard replacement of a diseased lower third of the aorta by a trouser graft is not feasible. Cellophane has been the most common agent employed, but these wraps have met with minimal success and on occasion has even been passed rectally. Kartchner and Lovett have reviewed the techniques and results of the later procedures replacing the cellophane wraps. In most instances a Dacron sheet was utilized. Six cases are reviewed from a solo private practice in which a standard trouser graft replacement was varied by using an alternative form of wrapping.

  6. Molecular mechanisms underlying the onset of degenerative aortic valve disease.

    PubMed

    Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi

    2009-01-01

    Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-beta(1), BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease. PMID:18766323

  7. A Comparison of ENO and TVD Schemes for the Computation of Shock-Turbulence Interaction

    NASA Astrophysics Data System (ADS)

    Hannappel, Ralf; Hauser, Thomas; Friedrich, Rainer

    1995-10-01

    A quantitative analysis of solutions to the Euler equations of fluid dynamis with the MUSCL, ENO-Harten, and efficient ENO-Shu algorithms is performed. Investigations of different test problems in one and two dimensions are presented. These are chosen as to model the shock-turbulence interaction in fluid dynamical systems. The notion of subcell resolution developed by Harten for the ENO schemes clearly improves the solution in one dimension; however, the effect is less prominent in a Strang-type extension to two dimensions. Our results confirm the superiority of the ENO schemes over the MUSCL approach in solving problems of flow fields with discontinuities which, at the same time, contain fine structure in its smooth parts.

  8. ED 02-1 ACUTE AORTIC SYNDROME.

    PubMed

    Song, Jae-Kwan

    2016-09-01

    The successful clinical introduction of various non-invasive imaging modalities has contributed to the establishment of 'acute aortic syndrome', a relatively new clinical syndrome incorporating several disease entities with similar clinical features (at the time of clinical presentation). Aortic dissection (AD) with intimal flap and two aortic channels (true and false lumens) is the most important disease entity in acute aortic syndrome. Clinical characteristics of AD have been established, with standardized treatment strategies depending on the affected site of the aorta. For the past several decades, variant forms of classic AD, including aortic intramural hematoma (IMH) and incomplete dissection, have been increasingly diagnosed in routine clinical practice worldwide, and imaging findings characteristic of these variant forms have been established for their differential diagnosis. As imaging findings, rather than clinical features, are critical for the differential diagnosis of acute aortic syndrome, careful interpretation of imaging results is necessary for accurate diagnosis and better clinical decision-making, thus improving patient outcomes. IMH is probably the most important variant form of classic AD and has been the source of intense controversy regarding its pathogenesis and optimal treatment options. Clinical reports regarding outcomes of patients with IMH from different centers have shown conflicting results and risk stratification based on imaging findings remains a challenging clinical issue.Intimal tears can have a very wide spectrum. For example, a stellate or linear intimal tear can involve the exposure of the underlying aortic media or adventitial layers but without the progression and separation of the medial layers, resulting in extensive undermining of the intimal layers. This incomplete dissection, characterized by an intimal tear without an intimal flap or hematoma, was reported to be present in 9 of 181 (5%) consecutive patients with

  9. Upregulation of ERK1/2-eNOS via AT2 Receptors Decreases the Contractile Response to Angiotensin II in Resistance Mesenteric Arteries from Obese Rats

    PubMed Central

    Hagihara, Graziela N.; Lobato, Nubia S.; Filgueira, Fernando P.; Akamine, Eliana H.; Aragão, Danielle S.; Casarini, Dulce E.; Carvalho, Maria Helena C.; Fortes, Zuleica B.

    2014-01-01

    It has been clearly established that mitogen-activated protein kinases (MAPKS) are important mediators of angiotensin II (Ang II) signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese) and non-obese Wistar rats (control) were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats. PMID:25170617

  10. Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells.

    PubMed

    Headley, Colwyn A; DiSilvestro, David; Bryant, Kelsey E; Hemann, Craig; Chen, Chun-An; Das, Amlan; Ziouzenkova, Ouliana; Durand, Grégory; Villamena, Frederick A

    2016-03-15

    Hyperglycemia has been implicated in the development of endothelial dysfunction through heightened ROS production. Since nitrones reverse endothelial nitric oxide synthase (eNOS) dysfunction, increase antioxidant enzyme activity, and suppress pro-apoptotic signaling pathway and mitochondrial dysfunction from ROS-induced toxicity, the objective of this study was to determine whether nitrone spin traps DMPO, PBN and PBN-LA were effective at duplicating these effects and improving glucose uptake in an in vitro model of hyperglycemia-induced dysfunction using bovine aortic endothelial cells (BAEC). BAEC were cultured in DMEM medium with low (5.5mM glucose, LG) or high glucose (50mM, HG) for 14 days to model in vivo hyperglycemia as experienced in humans with metabolic disease. Improvements in cell viability, intracellular oxidative stress, NO and tetrahydrobiopterin (BH4)​ levels, mitochondrial membrane potential, glucose transport, and activity of antioxidant enzymes were measured from single treatment of BAEC with nitrones for 24h after hyperglycemia. Chronic hyperglycemia significantly increased intracellular ROS by 50%, decreased cell viability by 25%, reduced NO bioavailability by 50%, and decreased (BH4) levels by 15% thereby decreasing NO production. Intracellular glucose transport and superoxide dismutase (SOD) activity were also decreased by 50% and 25% respectively. Nitrone (PBN and DMPO, 50 μM) treatment of BAEC grown in hyperglycemic conditions resulted in the normalization of outcome measures except for SOD and catalase activities. Our findings demonstrate that the nitrones reverse the deleterious effects of hyperglycemia in BAEC. We believe that in vivo testing of these nitrone compounds in models of cardiometabolic disease is warranted.

  11. Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells.

    PubMed

    Headley, Colwyn A; DiSilvestro, David; Bryant, Kelsey E; Hemann, Craig; Chen, Chun-An; Das, Amlan; Ziouzenkova, Ouliana; Durand, Grégory; Villamena, Frederick A

    2016-03-15

    Hyperglycemia has been implicated in the development of endothelial dysfunction through heightened ROS production. Since nitrones reverse endothelial nitric oxide synthase (eNOS) dysfunction, increase antioxidant enzyme activity, and suppress pro-apoptotic signaling pathway and mitochondrial dysfunction from ROS-induced toxicity, the objective of this study was to determine whether nitrone spin traps DMPO, PBN and PBN-LA were effective at duplicating these effects and improving glucose uptake in an in vitro model of hyperglycemia-induced dysfunction using bovine aortic endothelial cells (BAEC). BAEC were cultured in DMEM medium with low (5.5mM glucose, LG) or high glucose (50mM, HG) for 14 days to model in vivo hyperglycemia as experienced in humans with metabolic disease. Improvements in cell viability, intracellular oxidative stress, NO and tetrahydrobiopterin (BH4)​ levels, mitochondrial membrane potential, glucose transport, and activity of antioxidant enzymes were measured from single treatment of BAEC with nitrones for 24h after hyperglycemia. Chronic hyperglycemia significantly increased intracellular ROS by 50%, decreased cell viability by 25%, reduced NO bioavailability by 50%, and decreased (BH4) levels by 15% thereby decreasing NO production. Intracellular glucose transport and superoxide dismutase (SOD) activity were also decreased by 50% and 25% respectively. Nitrone (PBN and DMPO, 50 μM) treatment of BAEC grown in hyperglycemic conditions resulted in the normalization of outcome measures except for SOD and catalase activities. Our findings demonstrate that the nitrones reverse the deleterious effects of hyperglycemia in BAEC. We believe that in vivo testing of these nitrone compounds in models of cardiometabolic disease is warranted. PMID:26774452

  12. The role of eNOS phosphorylation in causing drug-induced vascular injury.

    PubMed

    Tobin, Grainne A McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; González, Carlos; Bancos, Simona; Zhang, Leshuai; Lawton, Michael P; Enerson, Bradley E; Weaver, James L

    2014-06-01

    Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.

  13. Ascending-to-descending aortic bypass and aortic valve replacement for concomitant severe aortic coarctation and aortic stenosis.

    PubMed

    Chu, Michael W A; Adams, Corey; Torres, Pedro

    2011-04-01

    We present a 33-year-old male with severe, symptomatic aortic coarctation and aortic stenosis assessed on a humanitarian medical mission to a developing country. Contemplating limited time and available resources, we performed a simultaneous single-stage approach with ascending-to-descending aortic bypass with a reinforced gortex graft and concomitant aortic valve replacement through a median sternotomy. The patient had an uneventful postoperative convalescence and was discharged on postoperative day 5. At 1-year follow-up, he was asymptomatic and doing well with good blood pressure control and complete equalization of upper and lower limb blood pressure measurements. Computed tomography and transthoracic echocardiography demonstrated a widely patent ascending-to-descending aortic bypass graft and a normally functioning prosthetic aortic valve, respectively. In developing countries where health care resources are limited, a combined approach with an extra-anatomic, thoracic aortic bypass, and aortic valve replacement resulted in good early and 1-year outcomes. This procedure may represent the most effective surgical option for patients with concomitant aortic coarctation and aortic stenosis.

  14. Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases.

    PubMed

    Ni, Xiaojia; Wong, Siu Ling; Wong, Chi Ming; Lau, Chi Wai; Shi, Xiaogeng; Cai, Yefeng; Huang, Yu

    2014-01-01

    Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2 (∙-)) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy. Results. ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2 in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reduced O2 (∙-) accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2. Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP's role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation. PMID:25258643

  15. The effects of PBDE-209 exposure during pregnancy on placental ET-1 and eNOS expression and the birth weight of offspring.

    PubMed

    Du, Peili; Li, Zhihua; Du, Lili; Zhang, Huili; Zhou, Yanmei; Sun, Wen; Xiao, Xue; He, Yutian; Sun, Bin; Yu, Yanhong; Chen, Dunjin

    2015-06-01

    Decabrominated diphenyl ether (PBDE-209) is a persistent organic pollutant. Gestational exposure to PBDE-209 can accumulate in pregnant women and fetuses via the placenta and umbilical cord, affecting perinatal outcome. In this study, pregnant Sprague-Dawley (SD) rats were randomly divided into five groups and intragastrically administered peanut oil (vehicle) 1, 5 and 10mg/kg by body weight (b.w.) of PBDE-209, or nothing (control) from day 0 (G0) to day 21 (G21) gestation, respectively. Placental samples were collected on G21 by cesarean section. The mRNA and protein expressions of ET-1, eNOS and iNOS in the placenta were examined using qRT-PCR and Western blot, respectively. Total nitric oxide (NO) in the placenta was measured using a specific ELISA kit. Compared with the control and vehicle groups, the mRNA expression of ET-1 and iNOS in the placenta was gradually and significantly increased after exposure to increasing concentrations of PBDE-209 (P<0.05), while the mRNA level of eNOS in the placenta was gradually and significantly reduced after exposure to increasing concentrations of PBDE-209 (P<0.05). The expression trends of ET-1, eNOS and iNOS proteins were consistent with those of mRNA expression. Interestingly, the production of total NO was significantly increased after exposure to 5 and 10mg/kg b.w. PBDE-209 (P<0.05). Finally, the birth weight of the offspring rats was significantly reduced after maternal exposure to 5 and 10 mg/kg b.w. PBDE-209 compared with the control and vehicle groups (P<0.05). These results suggest that PBDE-209 exposure during pregnancy upregulates ET-1 and iNOS expression, but decreases eNOS expression in the placenta, as well as reduces the birth weight of offspring.

  16. Aortic dissection presenting as gait disturbance: a case report.

    PubMed

    Estreicher, Michael; Portale, Joseph; Lopez, Bernard

    2013-01-01

    Emergency medicine dogma traditionally teaches that aortic dissection presents as tearing chest pain, radiating to the back. This case report describes a 55-year-old woman presenting with a left homonymous hemianopsia and resultant gait disturbance. Initial head computed tomography demonstrated a right parietal infarct, and chest radiograph demonstrated a markedly widened mediastinum. Acute Stanford type A aortic dissection was subsequently confirmed. This report provides further evidence for atypical, painless presentations of aortic dissection. Given recent literature on the increasing prevalence of painless dissection, the disease entity should be included in the differential diagnosis for stroke, and a simple portable chest x-ray should always be obtained before administering thrombolytics.

  17. Redox-Sensitive Up-Regulation of eNOS by Purple Grape Juice in Endothelial Cells: Role of PI3-Kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a

    PubMed Central

    Rashid, Sherzad; Kim, Jong Hun; Frota Madeira, Socorro Vanesca; Bronner, Christian; Schini-Kerth, Valérie B.

    2013-01-01

    The vascular protective effect of grape-derived polyphenols has been attributable, in part, to their direct action on blood vessels by stimulating the endothelial formation of nitric oxide (NO). The aim of the present study was to determine whether Concord grape juice (CGJ), which contains high levels of polyphenols, stimulates the expression of endothelial NO synthase (eNOS) in porcine coronary artery endothelial cells and, if so, to determine the signaling pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein levels and this effect is associated with an increased formation of NO in endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated with an increased eNOS mRNA stability and inhibited by antioxidants such as MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3-kinase), SB 203580 (an inhibitor of p38 MAPK), and SP 600125 (an inhibitor of JNK). Moreover, CGJ induced the formation of reactive oxygen species (ROS) in endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1 and FoxO3a, which regulate negatively eNOS expression, and this effect is prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover, chromatin immunoprecipitation assay indicated that the FoxO3a protein is associated with the eNOS promoter in control cells and that CGJ induced its dissociation. Thus, the present study indicates that CGJ up-regulates the expression of eNOS mRNA and protein leading to an increased formation of NO in endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression of the eNOS gene. PMID:23533577

  18. First direct aortic retrievable transcatheter aortic valve implantation in humans.

    PubMed

    Chandrasekhar, Jaya; Glover, Chris; Labinaz, Marino; Ruel, Marc

    2014-11-01

    We describe 2 cases in which transcatheter aortic valve implantation was performed with a Portico prosthesis (St Jude Medical, St Paul, MN) through a direct aortic approach. In 1 of the cases, prosthesis retrieval was needed during the procedure and was essential to the successful outcome. This is the first report, to our knowledge, of direct aortic Portico prosthesis implantation, and it highlights the significance of the retrievable nature of this device. PMID:25442452

  19. 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.

  20. Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely associated with the risk of ischemic stroke development for Asians: meta-analysis of epidemiological studies.

    PubMed

    Guo, Xiaolong

    2014-01-01

    Although the relationships between endothelial nitric oxide synthase (eNOS) gene polymorphisms (including G894T, VNTR and T786C) and risk of ischemic stroke (IS) have been extensively studied, controversial results have been reported. The aim of this study was to assess the relationships between them by using a meta-analysis. Literatures were retrieved through the following databases: Medline, Embase and Wangfang (updated to January 1st, 2013). Fixed- or random-effects model was used to calculate pooled odds ratio and 95 % confidence interval (OR and 95 % CI). A total of 31 case-control studies including 8,547 patients and 9,117 controls were included in this meta-analysis eventually. For eNOS G894T polymorphism, the results indicated that TT genotype was significantly associated with increased risk of IS incidence compared to G allele (OR and 95 % CI 1.25 (1.09-1.42) for TT vs. GT+GG, P < 0.001). When subgroup analysis was conducted according to ethnicities, T allele was significantly associated with risk of IS for Asians rather than for Caucasians. For eNOS VNTR polymorphism, 4aa genotype was significantly associated with risk of IS incidence compared to 4bb genotype (OR (95 % CI) 2.22 (1.66-2.97) for aa vs. bb, P < 0.001). Similarly, when subgroup analyses were conducted, 4aa was closely associated with increased risk of IS for Asians rather than for Caucasians. For eNOS T786C polymorphism, it was not associated with risk of IS incidence. In conclusion, this study indicated that eNOS 894T and VNTR 4a allele was significantly associated with risk of IS incidence for Asians. However, eNOS T786C polymorphism was not a likely risk factor for IS incidence.

  1. Mechanics of the pulmonary valve in the aortic position.

    PubMed

    Soares, A L F; van Geemen, D; van den Bogaerdt, A J; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2014-01-01

    Mathematical models can provide valuable information to assess and evaluate the mechanical behavior and remodeling of native tissue. A relevant example when studying collagen remodeling is the Ross procedure because it involves placing the pulmonary autograft in the more demanding aortic valve mechanical environment. The objective of this study was therefore to assess and evaluate the mechanical differences between the aortic valve and pulmonary valve and the remodeling that may occur in the pulmonary valve when placed in the aortic position. The results from biaxial tensile tests of pairs of human aortic and pulmonary valves were compared and used to determine the parameters of a structurally based constitutive model. Finite element analyzes were then performed to simulate the mechanical response of both valves to the aortic diastolic load. Additionally, remodeling laws were applied to assess the remodeling of the pulmonary valve leaflet to the new environment. The pulmonary valve showed to be more extensible and less anisotropic than the aortic valve. When exposed to aortic pressure, the pulmonary leaflet appeared to remodel by increasing its thickness and reorganizing its collagen fibers, rotating them toward the circumferential direction. PMID:24035437

  2. [Stent Grafting for Aortic Dissection].

    PubMed

    Uchida, Naomichi

    2016-07-01

    The purpose of stent graft for aortic dissection is to terminate antegrade blood flow into the false lumen through primary entry. Early intervention for primary entry makes excellent aortic remodeling and emergent stent grafting for complicated acute type B aortic dissection is supported as a class I. On the other hand stent grafting for chronic aortic dissection is controversial. Early stent grafting is considered with in 6 months after on-set if the diameter of the descending aorta is more than 40 mm. Additional interventions for residual false lumen on the downstream aorta are still required. Stent graft for re-entry, candy-plug technique, and double stenting, other effective re-interventions were reported. Best treatment on the basis of each anatomical and physical characteristics should be selected in each institution. Frozen elephant trunk is alternative procedure for aortic dissection without the need to take account of proximal anatomical limitation and effective for acute type A aortic dissection. PMID:27440026

  3. Lipid Interventions in Aortic Valvular Disease.

    PubMed

    Choi, Kwang Jin; Tsomidou, Christiana; Lerakis, Stamatios; Madanieh, Raef; Vittorio, Timothy J; Kosmas, Constantine E

    2015-10-01

    Aortic valve stenosis is the most common valvular disease in the elderly population. Presently, there is increasing evidence that aortic stenosis (AS) is an active process of lipid deposition, inflammation, fibrosis and calcium deposition. The pathogenesis of AS shares many similarities to that of atherosclerosis; therefore, it was hypothesized that certain lipid interventions could prevent or slow the progression of aortic valve stenosis. Despite the early enthusiasm that statins may slow the progression of AS, recent large clinical trials did not consistently demonstrate a decrease in the progression of AS. However, some researchers believe that statins may have a benefit early on in the disease process, where inflammation (and not calcification) is the predominant process, in contrast to severe or advanced AS, where calcification (and not inflammation) predominates. Positron emission tomography using 18F-fluorodeoxyglucose and 18F-sodium fluoride can demonstrate the relative contributions of valvular calcification and inflammation in AS, and thus this method might potentially be useful in providing the answer as to whether lipid interventions at the earlier stages of AS would be more effective in slowing the progression of the disease. Currently, there is a strong interest in recombinant apolipoprotein A-1 Milano and in the development of new pharmacological agents, targeting reduction of lipoprotein (a) levels and possibly reduction of the expression of lipoprotein-associated phospholipase A2, as potential means to slow the progression of aortic valvular stenosis. PMID:26263237

  4. Aortic valve replacement with combined myocardial revascularisation.

    PubMed Central

    Jones, M; Schofield, P M; Brooks, N H; Dark, J F; Moussalli, H; Deiraniya, A K; Lawson, R A; Rahman, A N

    1989-01-01

    Early and late outcome was studied in 630 patients who underwent aortic valve replacement between 1974 and 1982. Group 1 (506 patients) did not have important coronary artery disease, group 2 (69 patients) had coronary artery disease and underwent coronary artery bypass grafting, and group 3 (55 patients) had coronary artery disease but did not undergo myocardial revascularisation. Early mortality (within 30 days of operation) was significantly lower for group 1 (6%) than for group 2 (13%) and for group 3 (16%). Operative mortality in all three groups was lower in patients operated on more recently. The three year survival of patients in group 1 (83%) was significantly higher than that of patients in group 3 (62%) but not than that of patients in group 2 (76%). The findings of this study suggest that the presence of coronary artery disease increases the risk of aortic valve replacement whether or not coronary artery grafting is performed. Myocardial revascularisation, however, seems to return patients with aortic valve and coronary artery disease to a survival curve similar to that of patients with isolated aortic valve disease. PMID:2788003

  5. A tailed primers protocol to identify the association of eNOS gene variable number of tandem repeats polymorphism with ischemic stroke in Chinese Han population by capillary electrophoresis.

    PubMed

    Tong, Yeqing; Yin, Xiaoxu; Wang, Zhihong; Zhan, Faxian; Zhang, Yanwei; Ye, Jianjun; Hou, Shuangyi; Geng, Yijie; Li, Yang; Guan, Xuhua; Jiang, Yongzhong; Zhang, Lingyao; Dai, Jifang; Mason, Katherine A; Liu, Jiafa; Lu, Zuxun; Cheng, Jinquan

    2013-04-01

    Endothelial nitric oxide synthase (eNOS) plays an important role in mediating endothelium-dependent vasodilatation and antithrombotic action and is thus involved in the development of ischemic stroke (IS). Controversial results regarding the association of eNOS gene variable number of tandem repeats (VNTR) polymorphism with IS have been reported by conventional PCR-polyacrylamide gel electrophoresis methods. We aimed to identify any common association of eNOS gene VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by CE with specially designed tailed primers in Chinese Han patients with IS (n=457) and matched elderly controls without IS (n=457). Significant differences in BMI, WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed between cases and controls. The distributions of eNOS VNTR polymorphism were not significantly associated with IS after adjustment for cardiovascular risk factors (OR=1.18, 95% CI: 0.82-1.69). This finding was consistent with the further meta-analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b+4a/4a genotype was significantly associated with IS risk with an OR of 1.54 (95% CI, 1.09-2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR, hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS. However, eNOS VNTR polymorphism may be not an independent major contributor for IS in Chinese Han population. The VNTR polymorphism might be associated with IS in Americans based on meta-analysis.

  6. HLA class I-mediated stress fiber formation requires ERK1/2 activation in the absence of an increase in intracellular Ca2+ in human aortic endothelial cells.

    PubMed

    Ziegler, Mary E; Jin, Yi-Ping; Young, Steven H; Rozengurt, Enrique; Reed, Elaine F

    2012-10-15

    Following transplantation, HLA class I antibodies targeting donor endothelium stimulate cell proliferation and migration, which contribute to the development of transplant vasculopathy and chronic allograft rejection. Dynamic remodeling of the actin cytoskeleton regulates cell proliferation and migration in endothelial cells (ECs), but the mechanism(s) involved remain incompletely understood. We explored anti-HLA class I antibody-mediated alterations of the cytoskeleton in human aortic ECs (HAECs) and contrasted these findings to thrombin-induced cytoskeleton remodeling. Our results identify two different signaling pathways leading to myosin light chain (MLC) phosphorylation in HAECs. Stimulation of HAECs with thrombin at 1 U/ml induced a robust elevation of intracellular Ca(2+) concentration, increased MLC phosphorylation, and promoted stress fiber formation via MLC kinase (MLCK) and Rho kinase (ROK) in an ERK-independent manner. In contrast, HAECs stimulated with HLA class I antibodies did not promote any detectable change in intracellular Ca(2+) concentration but instead induced MLC phosphorylation and stress fiber assembly via MLCK and ROK in an ERK1/2-dependent manner. Stimulation of HAECs with low-dose thrombin (1 mU/ml) induced signaling cascades that were similar to stimulation with HLA class I antibodies. HLA class I antibodies also stimulated the translocation of mammalian target of rapamycin complex 2 (mTORC2) and ERK1/2 from the cytoplasm to the plasma membrane independently of stress fiber assembly. These findings identify novel roles for HLA class I signaling in ECs and provide new insights into the role of ERK1/2 and mTORC2 in cytoskeleton regulation, which may be important in promoting transplant vasculopathy, tumor angiogenesis, and atherosclerosis. PMID:22914643

  7. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

    SciTech Connect

    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun; Wang, Yuchan; He, Song

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  8. (−)-Epicatechin activation of endothelial cell eNOS, NO and related signaling pathways

    PubMed Central

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

    2010-01-01

    Recent reports indicate that (−)-epicatechin can exert cardioprotective actions, which may involve eNOS-mediated nitric oxide production in endothelial cells. However, the mechanism by which (−)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (−)-epicatechin-induced effects on eNOS, utilizing human coronary artery endothelial cells in culture. Treatment of cells with (−)-epicatechin leads to time- and dose-dependent effects, which peaked at 10 min at 1 μmol/L. (−)-Epicatechin treatment activates eNOS via serine-633 and serine-1177 phosphorylation and threonine-495 dephosphorylation. Using specific inhibitors, we have established the participation of the PI3K pathway in eNOS activation. (−)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (−) epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (−)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (−)-epicatechin-treated cells. The inhibitory effects of the pre-incubation of cells with the CaMKII inhibitor KN-93 indicate that (−)-epicatechin-induced eNOS activation is at least partially mediated via the Ca2+/CaMKII pathway. The (−)-epicatechin stereoisomer catechin was only able to partially stimulate nitric oxide production in cells. Altogether, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (−)-epicatechin, which may mediate its cardiovascular effects. PMID:20404222

  9. 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.

  10. 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.

  11. 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. PMID:26118429

  12. Almanac 2014: aortic valve disease.

    PubMed

    Otto, Catherine M

    2015-06-01

    The past few years have seen major advances in the diagnosis of aortic valve disease and in our understanding of the pathophysiology of disease. In addition, transcatheter aortic valve implantation has transformed our clinical management options. This article summarises new aortic valve disease research published in Heart in 2013 and 2014, within the context of other major studies published in general medical journals, including a discussion of the potential impact of these new research findings on the clinical approach to management of adults with aortic valve disease.

  13. β3-Adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation.

    PubMed

    Niu, Xiaolin; Zhao, Lianyou; Li, Xue; Xue, Yusheng; Wang, Bin; Lv, Zongqiang; Chen, Jianghong; Sun, Dongdong; Zheng, Qiangsun

    2014-01-01

    β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Animals were administrated with β3-AR agonist BRL37344 (BRL) or β3-AR inhibitor SR59230A (SR) respectively at 0.1 mg/kg/hour one day after MI operation. The scar area, cardiac function and the apoptosis of myocardial were assessed by Masson's trichrome stain, echocardiography and TUNEL assay respectively. Western blot analysis was performed to elucidate the expressions of target proteins. β3-AR activation with BRL administration significantly attenuated fibrosis and decreased scar area after MI. Moreover, BRL also preserved heart function, and reduced the apoptosis of cardiomyocyte induced by MI. Furthermore, BRL treatment altered the phosphorylation status of endothelial NOS (eNOS) and increased the expression of neuronal NOS (nNOS). These results suggested that β3-AR stimulation has a substantial effect on recovery of heart function. In addition, the activations of both eNOS and nNOS may be associated with the cardiac protective effects of β3-AR.

  14. Infrarenal Aortic Occlusion

    PubMed Central

    Traverso, L. W.; Baker, J. D.; Dainko, E. A.; Machleder, H. I.

    1978-01-01

    Twenty-eight patients with total occlusion of the infrarenal aorta have been seen at the UCLA Hospitals in the past 11 years. Claudication was the presenting complaint in all but one patient, with one-third having ischemic rest pain. The average age of these patients was 54 years, and their histories revealed a surprising absence of myocardial infarction, stroke, or diabetes, although 40% had essential hypertension. Heavy tobacco use, however, was characteristic of the entire group. Arteriography proved valuable in identifying and characterizing the vascular abnormalities, but posed problems in technique and interpretation. Significant distal arterial disease was detected radiographically in only 21% of these patients. Operative correction of the aortic occlusion was performed on 26 patients, 18 by aortic bypass grafts and eight by aorto-iliac endarterectomy, with one early postoperative death. Although the thrombus extended to the renal artery origins in 77% of the cases, a well-designed technical approach did not require renal artery occlusion. Using serial creatinine determinations, one case of renal insufficiency was detected which was associated with prolonged postoperative hypotension. Although the extent of distal disease was more severe in those who underwent bypass, symptoms of claudication returned earlier and were more prominent in the endarterectomy group. This recurrence of systems was not favorably altered by sympathectomy performed concomitantly with the initial procedure. Even though this condition seems to pose difficult technical obstacles and has a poor prognosis, infrarenal aortic occlusion can be successfully treated by aortic bypass, with favorable long-term results, if particular attention is paid to elements of the preoperative evaluation and the intraoperative technical requirements peculiar to this relatively uncommon disease entity. ImagesFig. 1.Fig. 2.Fig. 3. PMID:646479

  15. Neuroprotection during aortic surgery.

    PubMed

    Lindsay, Helen; Srinivas, Coimbatore; Djaiani, George

    2016-09-01

    Neurological injury is a major limitation of aortic surgery, whether it involves spinal cord injury following intervention to the thoracoabdominal aorta, or stroke following surgery on the arch and ascending aorta. Despite an extensive body of literature and various proposals, a completely effective strategy to prevent or treat neurological injury remains elusive. In this article, we summarise the evidence for established and emerging strategies, and review current concepts in pathophysiology and risk assessment as they relate to neurological injury. PMID:27650340

  16. Cytokine amplification and macrophage effector functions in aortic inflammation and abdominal aortic aneurysm formation.

    PubMed

    Ijaz, Talha; Tilton, Ronald G; Brasier, Allan R

    2016-08-01

    On April 29, 2015, Son and colleagues published an article entitled "Granulocyte macrophage colony-stimulating factor (GM-CSF) is required for aortic dissection/intramural haematoma" in Nature Communications. The authors observed that the heterozygous Kruppel-like transcription factor 6 (KLF6) deficiency or absence of myeloid-specific KLF6 led to upregulation of macrophage GM-CSF expression, promoted the development of aortic hematoma/dissection, and stimulated abdominal aortic aneurysm (AAA) formation when the vessel wall was subjected to an inflammatory stimulus. The additional findings of increased adventitial fibrotic deposition, marked infiltration of macrophages, and increased expression of matrix metalloprotease-9 (MMP-9) and IL-6 were blocked with neutralizing GM-CSF antibodies, or recapitulated in normal mice with excess GM-CSF administration. The authors concluded that GM-CSF is a key regulatory molecule in the development of AAA and further suggested that activation of GM-CSF is independent of the transforming growth factor β (TGFβ)-Smad pathway associated with the Marfan aortic pathology. In this perspective, we expand on this mechanism, drawing from previous studies implicating a similar essential role for IL-6 signaling in macrophage activation, Th17 expansion and aortic dissections. We propose a sequential "two-hit" model of vascular inflammation involving initial vascular injury followed by recruitment of Ly6C(hi) macrophages. Aided by fibroblast interactions inflammatory macrophages produce amplification of IL-6 and GM-CSF expression that converge on a common, pathogenic Janus kinase (JAK)-signal transducers and activations of transcription 3 (STAT3) signaling pathway. This pathway stimulates effector functions of macrophages, promotes differentiation of Th17 lymphocytes and enhances matrix metalloproteinase expression, ultimately resulting in deterioration of vascular wall structural integrity. Further research evaluating the impact of

  17. Cytokine amplification and macrophage effector functions in aortic inflammation and abdominal aortic aneurysm formation

    PubMed Central

    Ijaz, Talha; Tilton, Ronald G.

    2016-01-01

    On April 29, 2015, Son and colleagues published an article entitled “Granulocyte macrophage colony-stimulating factor (GM-CSF) is required for aortic dissection/intramural haematoma” in Nature Communications. The authors observed that the heterozygous Kruppel-like transcription factor 6 (KLF6) deficiency or absence of myeloid-specific KLF6 led to upregulation of macrophage GM-CSF expression, promoted the development of aortic hematoma/dissection, and stimulated abdominal aortic aneurysm (AAA) formation when the vessel wall was subjected to an inflammatory stimulus. The additional findings of increased adventitial fibrotic deposition, marked infiltration of macrophages, and increased expression of matrix metalloprotease-9 (MMP-9) and IL-6 were blocked with neutralizing GM-CSF antibodies, or recapitulated in normal mice with excess GM-CSF administration. The authors concluded that GM-CSF is a key regulatory molecule in the development of AAA and further suggested that activation of GM-CSF is independent of the transforming growth factor β (TGFβ)-Smad pathway associated with the Marfan aortic pathology. In this perspective, we expand on this mechanism, drawing from previous studies implicating a similar essential role for IL-6 signaling in macrophage activation, Th17 expansion and aortic dissections. We propose a sequential “two-hit” model of vascular inflammation involving initial vascular injury followed by recruitment of Ly6Chi macrophages. Aided by fibroblast interactions inflammatory macrophages produce amplification of IL-6 and GM-CSF expression that converge on a common, pathogenic Janus kinase (JAK)-signal transducers and activations of transcription 3 (STAT3) signaling pathway. This pathway stimulates effector functions of macrophages, promotes differentiation of Th17 lymphocytes and enhances matrix metalloproteinase expression, ultimately resulting in deterioration of vascular wall structural integrity. Further research evaluating the impact of

  18. Contemporary Use of Balloon Aortic Valvuloplasty in the Era of Transcatheter Aortic Valve Implantation

    PubMed Central

    Hui, Dawn S.; Shavelle, David M.; Cunningham, Mark J.; Matthews, Ray V.; Starnes, Vaughn A.

    2014-01-01

    The development of transcatheter aortic valve implantation (TAVI) has increased the use of balloon aortic valvuloplasty (BAV) in treating aortic stenosis. We evaluated our use of BAV in an academic tertiary referral center with a developing TAVI program. We reviewed 69 consecutive stand-alone BAV procedures that were performed in 62 patients (mean age, 77 ± 10 yr; 62% men; baseline mean New York Heart Association functional class, 3 ± 1) from January 2009 through December 2012. Enrollment for the CoreValve® clinical trial began in January 2011. We divided the study cohort into 2 distinct periods, defined as pre-TAVI (2009–2010) and TAVI (2011–2012). We reviewed clinical, hemodynamic, and follow-up data, calculating each BAV procedure as a separate case. Stand-alone BAV use increased 145% from the pre-TAVI period to the TAVI period. The mean aortic gradient reduction was 13 ± 10 mmHg. Patients were successfully bridged as intended to cardiac or noncardiac surgery in 100% of instances and to TAVI in 60%. Five patients stabilized with BAV subsequently underwent surgical aortic valve replacement with no operative deaths. The overall in-hospital mortality rate (17.4%) was highest in emergent patients (61%). The implementation of a TAVI program was associated with a significant change in BAV volumes and indications. Balloon aortic valvuloplasty can successfully bridge patients to surgery or TAVI, although least successfully in patients nearer death. As TAVI expands to more centers and higher-risk patient groups, BAV might become integral to collaborative treatment decisions by surgeons and interventional cardiologists. PMID:25425977

  19. Cytokine amplification and macrophage effector functions in aortic inflammation and abdominal aortic aneurysm formation

    PubMed Central

    Ijaz, Talha; Tilton, Ronald G.

    2016-01-01

    On April 29, 2015, Son and colleagues published an article entitled “Granulocyte macrophage colony-stimulating factor (GM-CSF) is required for aortic dissection/intramural haematoma” in Nature Communications. The authors observed that the heterozygous Kruppel-like transcription factor 6 (KLF6) deficiency or absence of myeloid-specific KLF6 led to upregulation of macrophage GM-CSF expression, promoted the development of aortic hematoma/dissection, and stimulated abdominal aortic aneurysm (AAA) formation when the vessel wall was subjected to an inflammatory stimulus. The additional findings of increased adventitial fibrotic deposition, marked infiltration of macrophages, and increased expression of matrix metalloprotease-9 (MMP-9) and IL-6 were blocked with neutralizing GM-CSF antibodies, or recapitulated in normal mice with excess GM-CSF administration. The authors concluded that GM-CSF is a key regulatory molecule in the development of AAA and further suggested that activation of GM-CSF is independent of the transforming growth factor β (TGFβ)-Smad pathway associated with the Marfan aortic pathology. In this perspective, we expand on this mechanism, drawing from previous studies implicating a similar essential role for IL-6 signaling in macrophage activation, Th17 expansion and aortic dissections. We propose a sequential “two-hit” model of vascular inflammation involving initial vascular injury followed by recruitment of Ly6Chi macrophages. Aided by fibroblast interactions inflammatory macrophages produce amplification of IL-6 and GM-CSF expression that converge on a common, pathogenic Janus kinase (JAK)-signal transducers and activations of transcription 3 (STAT3) signaling pathway. This pathway stimulates effector functions of macrophages, promotes differentiation of Th17 lymphocytes and enhances matrix metalloproteinase expression, ultimately resulting in deterioration of vascular wall structural integrity. Further research evaluating the impact of

  20. Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis

    PubMed Central

    2010-01-01

    Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector. Conclusions These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium. PMID:20875110

  1. Serine 1179 Phosphorylation of Endothelial Nitric Oxide Synthase Increases Superoxide Generation and Alters Cofactor Regulation.

    PubMed

    Peng, Hu; Zhuang, Yugang; Harbeck, Mark C; He, Donghong; Xie, Lishi; Chen, Weiguo

    2015-01-01

    Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. In addition to producing NO, eNOS can also generate superoxide (O2-.) in the absence of the cofactor tetrahydrobiopterin (BH4). Previous studies have shown that bovine eNOS serine 1179 (Serine 1177/human) phosphorylation critically modulates NO synthesis. However, the effect of serine 1179 phosphorylation on eNOS superoxide generation is unknown. Here, we used the phosphomimetic form of eNOS (S1179D) to determine the effect of S1179 phosphorylation on superoxide generating activity, and its sensitivity to regulation by BH4, Ca2+, and calmodulin (CAM). S1179D eNOS exhibited significantly increased superoxide generating activity and NADPH consumption compared to wild-type eNOS (WT eNOS). The superoxide generating activities of S1179D eNOS and WT eNOS did not differ significantly in their sensitivity to regulation by either Ca2+ or CaM. The sensitivity of the superoxide generating activity of S1179D eNOS to inhibition by BH4 was significantly reduced compared to WT eNOS. In eNOS-overexpressing 293 cells, BH4 depletion with 10mM DAHP for 48 hours followed by 50ng/ml VEGF for 30 min to phosphorylate eNOS S1179 increased ROS accumulation compared to DAHP-only treated cells. Meanwhile, MTT assay indicated that overexpression of eNOS in HEK293 cells decreased cellular viability compared to control cells at BH4 depletion condition (P<0.01). VEGF-mediated Serine 1179 phosphorylation further decreased the cellular viability in eNOS-overexpressing 293 cells (P<0.01). Our data demonstrate that eNOS serine 1179 phosphorylation, in addition to enhancing NO production, also profoundly affects superoxide generation: S1179 phosphorylation increases superoxide production while decreasing sensitivity to the inhibitory effect of BH4 on this activity. PMID:26560496

  2. Transcatheter aortic valve implantation.

    PubMed

    Nielsen, Hans Henrik Møller

    2012-12-01

    Transcatheter aortic valve implantation (TAVI) was introduced experimentally in 1989, based on a newly developed heart valve prosthesis - the stentvalve. The valve was invented by a Danish cardiologist named Henning Rud Andersen. The new valve was revolutionary. It was foldable and could be inserted via a catheter through an artery in the groin, without the need for heart lung machine. This allowed for a new valve implantation technique, much less invasive than conventional surgical aortic valve replacement (SAVR). Surgical aortic valve replacement is safe and improves symptoms along with survival. However, up to 1/3 of patients with aortic valve stenosis cannot complete the procedure due to frailty. The catheter technique was hoped to provide a new treatment option for these patients. The first human case was in 2002, but more widespread clinical use did not begin until 2006-2010. Today, in 2011, more than 40,000 valves have been implanted worldwide. Initially, because of the experimental character of the procedure, TAVI was reserved for patients who could not undergo SAVR due to high risk. The results in this group of patients were promising. The procedural safety was acceptable, and the patients experienced significant improvements in their symptoms. Three of the papers in this PhD-thesis are based on the outcome of TAVI at Skejby Hospital, in this high-risk population [I, II and IV]. Along with other international publications, they support TAVI as being superior to standard medical treatment, despite a high risk of prosthetic regurgitation. These results only apply to high-risk patients, who cannot undergo SAVR. The main purpose of this PhD study has been to investigate the quality of TAVI compared to SAVR, in order to define the indications for this new procedure. The article attached [V] describes a prospective clinical randomised controlled trial, between TAVI to SAVR in surgically amenable patients over 75 years of age with isolated aortic valve stenosis

  3. Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway.

    PubMed

    Yang, Jin-Ting; Qian, Ling-Bo; Zhang, Feng-Jiang; Wang, Jue; Ai, Heng; Tang, Li-Hui; Wang, Hui-Ping

    2015-04-01

    Myocardial ischemia/reperfusion (I/R) injury in diabetes is associated with oxidative stress, endothelial nitric oxide synthase (eNOS) dysfunction, and mitochondrial collapse, whereas luteolin is known to protect the cardiovascular system against diabetes and I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in diabetic rats by affecting eNOS and the mitochondrial permeability transition pore (mPTP). After diabetic rats were produced by streptozotocin treatment (65 mg/kg) for 3 weeks, luteolin (100 mg·kg·d) or L-NAME (25 mg·kg·d) was administered intragastrically for 2 weeks. Hearts were then isolated and subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. Pretreatment with luteolin significantly improved left ventricular function and coronary flow throughout reperfusion, increased cardiac tissue viability and manganese superoxide dismutase (MnSOD) activity, and reduced coronary lactate dehydrogenase release, and the myocardial malonaldehyde level in diabetic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by L-NAME. Luteolin also significantly upregulated eNOS expression in diabetic rat hearts after I/R. Ca-induced mPTP opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated diabetic rats, and this effect was attenuated by L-NAME. These findings indicate that luteolin protects the diabetic heart against I/R injury by upregulating the myocardial eNOS pathway, and downstream effects include the enhancement of MnSOD and inhibition of mPTP. PMID:25502309

  4. Pregnancy Adaptive Programming of Capacitative Entry Responses Alters NO Output in Vascular Endothelium: New Insights Into eNOS Regulation through Adaptive Cell Signaling

    PubMed Central

    Boeldt, DS; Yi, FX; Bird, IM

    2014-01-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, so supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as preeclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial nitric oxide synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca2+]i concentration in response to circulating hormones or physical forces. Herein we discuss how pregnancy specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca2+]i signaling responses as it is by eNOS expression and phosphorylation. By examining changes in [Ca2+]i signaling responses from HHVE, UAEC, and HUVEC in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (preeclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase ‘capacitative entry’ [Ca2+]i response, and the adapted response is lacking in preeclamptic pregnancies. Further, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca2+]i signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy, but may also apply to other common forms of hypertension. PMID:21555345

  5. Quadricuspid Aortic Valve: A Rare Congenital Cause of Aortic Insufficiency

    PubMed Central

    Vasudev, Rahul; Shah, Priyank; Bikkina, Mahesh; Shamoon, Fayez

    2016-01-01

    Quadricuspid aortic valve (QAV) is a rare congenital cardiac anomaly causing aortic regurgitation usually in the fifth to sixth decade of life. Earlier, the diagnosis was mostly during postmortem or intraoperative, but now with the advent of better imaging techniques such as transthoracic echocardiography, transesophageal echocardiography (TEE), and cardiac magnetic resonance imaging, more cases are being diagnosed in asymptomatic patients. We present a case of a 39-year-old male who was found to have QAV, with the help of TEE, while undergoing evaluation for a diastolic murmur. The patient was found to have Type B QAV with moderate aortic regurgitation. We also present a brief review of classification, pathophysiology, and embryological basis of this rare congenital anomaly. The importance of diagnosing QAV lies in the fact that majority of these patients will require surgery for aortic regurgitation and close follow-up so that aortic valve replacement/repair is done before the left ventricular decompensation occurs. PMID:27195176

  6. The expanding indications of transcatheter aortic valve implantation.

    PubMed

    Chiam, Paul T L; Ewe, See Hooi

    2016-03-01

    Transcatheter aortic valve implantation (TAVI), also known as transcatheter aortic valve replacement, is increasingly performed worldwide and is a technology that is here to stay. It has become the treatment of choice for inoperable patients and an alternative option for patients at high surgical risk with severe aortic stenosis. Early results of TAVI in intermediate-risk patients appear promising although larger randomized trial results are awaited before the widespread adoption of this technology in this big pool of patients. In patients with bicuspid aortic stenosis and degenerated surgical bioprostheses, TAVI has been shown to be feasible and relatively safe, though certain important considerations remain. Indications for TAVI are likely to grow as newer generation and improved devices and delivery systems become available.

  7. Minimally Invasive Techniques for Total Aortic Arch Reconstruction.

    PubMed

    Faulds, Jason; Sandhu, Harleen K; Estrera, Anthony L; Safi, Hazim J

    2016-01-01

    The cumulative experience with endovascular aortic repair in the descending thoracic and infrarenal aorta has led to increased interest in endovascular aortic arch reconstruction. Open total arch replacement is a robust operation that can be performed with excellent results. However, it requires cardiopulmonary bypass and circulatory arrest and, therefore, may not be tolerated by all patients. Minimally invasive techniques have been considered as an alternative and include hybrid arch debranching, parallel stent graft deployment in the chimney and snorkel configurations, and complete endovascular branched reconstruction with multi-branched devices. This review discusses the evolving use of endovascular techniques in the management of aortic arch pathology and considers their relevance in an era of safe and durable open aortic arch reconstruction.

  8. Minimally Invasive Techniques for Total Aortic Arch Reconstruction

    PubMed Central

    Faulds, Jason; Sandhu, Harleen K.; Estrera, Anthony L.; Safi, Hazim J.

    2016-01-01

    The cumulative experience with endovascular aortic repair in the descending thoracic and infrarenal aorta has led to increased interest in endovascular aortic arch reconstruction. Open total arch replacement is a robust operation that can be performed with excellent results. However, it requires cardiopulmonary bypass and circulatory arrest and, therefore, may not be tolerated by all patients. Minimally invasive techniques have been considered as an alternative and include hybrid arch debranching, parallel stent graft deployment in the chimney and snorkel configurations, and complete endovascular branched reconstruction with multi-branched devices. This review discusses the evolving use of endovascular techniques in the management of aortic arch pathology and considers their relevance in an era of safe and durable open aortic arch reconstruction. PMID:27127562

  9. Downregulation of the Yes-Associated Protein Is Associated with Extracellular Matrix Disorders in Ascending Aortic Aneurysms.

    PubMed

    Li, Haiyang; Jiang, Wenjian; Ren, Weihong; Guo, Dong; Guo, Jialong; Wang, Xiaolong; Liu, Yuyong; Lan, Feng; Du, Jie; Zhang, Hongjia

    2016-01-01

    Previous studies indicate that extracellular matrix (ECM) disorders lead to the apoptosis of Vascular Smooth Muscle Cells (VSMCs), which impairs the aortic wall by reducing the generation of elastic fibers, and ultimately result in ascending aortic aneurysm. The critical role of the Yes-associated protein (YAP) has been elucidated in cardiac/SMC proliferation during cardiovascular development. However, the association of YAP expression and extracellular matrix disorders in ascending aortic aneurysms is not clear. Here, we present for the first time that the downregulation of YAP in VSMCs is associated with ECM disorders of the media in ascending aortic aneurysms. We found that aortic ECM deteriorated with increased apoptotic VSMCs. Moreover, expression of YAP was dramatically reduced in the aortic walls of patients with ascending aortic aneurysms, while the normal aortic samples exhibited abundant YAP in the VSMCs. These results suggest that downregulation of YAP leads to apoptosis of VSMCs, which are essential for the homeostasis of the aortic wall. The resultant ECM disorders affect aortic structure and function and contribute to the development of ascending aortic aneurysms. In summary, through assessment of clinical samples, we revealed the association between downregulation of YAP in VSMCs and the development of ascending aortic aneurysms, providing new insight into the pathogenesis of this disease. PMID:26904131

  10. Transcatheter aortic valve implantation and simultaneous closure of associated paravalvular leak.

    PubMed

    Cockburn, James; Charlton, Thomas; Gomes, Arri; Trivedi, Uday; Hildick-Smith, David

    2016-01-01

    Paravalvular aortic regurgitation (PAR) following transcatheter aortic valve implantation (TAVI) is a complication which is associated with increased late mortality. When PAR is severe and refractory to standard corrective measures, case reports have now described the successful use of vascular plugs to treat PAR as a follow-up procedure. We describe a case of vascular plug implantation to reduce PAR immediately after implantation of the transcatheter aortic valve prosthesis.

  11. QT dispersion is reduced after valve replacement in patients with aortic stenosis

    PubMed Central

    Darbar, D; Cherry, C; Kerins, D

    1999-01-01

    OBJECTIVE—To investigate whether QT dispersion is a reliable index of the severity of aortic stenosis and left ventricular hypertrophy in the setting of aortic stenosis.
DESIGN—A retrospective analysis of the results of echocardiography and electrocardiography before and after aortic valve replacement.
SETTING—Tertiary centre.
PATIENTS—36 men (30 white and six black) with symptomatic aortic stenosis requiring valve replacement.
RESULTS—All patients had significant aortic stenosis (mean (SD) aortic valve area 0.68 (0.18) cm2) and evidence of left ventricular hypertrophy (left ventricular mass index (LVMI): 267 (90) g/m2). Before aortic valve replacement, QT dispersion was correlated with mean aortic valve area and LVMI (r = 0.697, p < 0.001, and r = 0.59, p < 2.4 × 10−6, respectively). QT dispersion and QT corrected for heart rate dispersion decreased from 133 (54) to 71 (33) ms and from 151 (64) to 94 (76) ms, respectively (p < 0.001 for both). LVMI regressed after aortic valve replacement to 190 (79) g/m2, p < 0.01.
CONCLUSIONS—QT dispersion is increased in association with LVMI in patients with significant symptomatic aortic stenosis. Aortic valve replacement reduces QT dispersion and LVMI. QT dispersion could be a useful indicator of risk and risk reduction in patients with significant symptomatic aortic stenosis.


Keywords: QT dispersion; left ventricular hypertrophy; aortic valve replacement PMID:10377301

  12. Aortic calcification produced by vitamin D3 plus nicotine.

    PubMed

    Niederhoffer, N; Bobryshev, Y V; Lartaud-Idjouadiene, I; Giummelly, P; Atkinson, J

    1997-01-01

    Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 +/- 87, n = 12 in VDN vs. 24 +/- 2 micromol g(-1) aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 +/- 17 and 254 +/- 15 in VDN vs. 655 +/- 56 and 588 +/- 30 microg g(-1) aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 +/- 1.8 in VDN vs. 6.7 +/- 0.5 10(6) dyn cm(-2) in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 +/- 6 in VDN vs. 136 +/- 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 +/- 0.10 in VDN vs. 2.24 +/- 0.07 g kg(-1) in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero- and arteriosclerosis.

  13. 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.

  14. Thoracic aortic aneurysms and pregnancy.

    PubMed

    Coulon, Capucine

    2015-11-01

    Half of acute aortic dissection in women under the age of 40 occurs during pregnancy or peripartum period. Marfan syndrome is the most common syndromic presentation of ascending aortic aneurysm, but other syndromes such as vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Turner syndrome also have ascending aortic aneurysms and the associated cardiovascular risk of aortic dissection and rupture. Management of aortic root aneurysm has been established in recent recommendations, even if levels of evidence are weak. Pregnancy and postpartum period should be followed very closely and determined to be at high risk. Guidelines suggest that women with aortopathy should be counseled against the risk of pregnancy and about the heritable nature of the disease prior to pregnancy.

  15. New Insights Into Aortic Diseases

    PubMed Central

    Kuivaniemi, Helena; Sakalihasan, Natzi; Lederle, Frank A.; Jones, Gregory T.; Defraigne, Jean-Olivier; Labropoulos, Nicos; Legrand, Victor; Michel, Jean-Baptiste; Nienaber, Christoph; Radermecker, Marc A.; Elefteriades, John A.

    2013-01-01

    The current state of research and treatment on aortic diseases was discussed in the “3rd International Meeting on Aortic Diseases” (IMAD3) held on October 4–6, 2012, in Liège, Belgium. The 3-day meeting covered a wide range of topics related to thoracic aortic aneurysms and dissections, abdominal aortic aneurysms, and valvular diseases. It brought together clinicians and basic scientists and provided an excellent opportunity to discuss future collaborative research projects for genetic, genomics, and biomarker studies, as well as clinical trials. Although great progress has been made in the past few years, there are still a large number of unsolved questions about aortic diseases. Obtaining answers to the key questions will require innovative, interdisciplinary approaches that integrate information from epidemiological, genetic, molecular biology, and bioengineering studies on humans and animal models. It is more evident than ever that multicenter collaborations are needed to accomplish these goals. PMID:26798669

  16. Thoracic aortic aneurysms and pregnancy.

    PubMed

    Coulon, Capucine

    2015-11-01

    Half of acute aortic dissection in women under the age of 40 occurs during pregnancy or peripartum period. Marfan syndrome is the most common syndromic presentation of ascending aortic aneurysm, but other syndromes such as vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome and Turner syndrome also have ascending aortic aneurysms and the associated cardiovascular risk of aortic dissection and rupture. Management of aortic root aneurysm has been established in recent recommendations, even if levels of evidence are weak. Pregnancy and postpartum period should be followed very closely and determined to be at high risk. Guidelines suggest that women with aortopathy should be counseled against the risk of pregnancy and about the heritable nature of the disease prior to pregnancy. PMID:26454306

  17. Painless Type B Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection

    PubMed Central

    Tolenaar, Jip L.; Hutchison, Stuart J.; Montgomery, Dan; O'Gara, Patrick; Fattori, Rosella; Pyeritz, Reed E.; Pape, Linda; Suzuki, Toru; Evangelista, Arturo; Moll, Frans L.; Rampoldi, Vincenzo; Isselbacher, Eric M.; Nienaber, Cristoph A.; Eagle, Kim A.; Trimarchi, Santi

    2013-01-01

    Introduction: The classical presentation of a patient with Type B acute aortic dissection (TBAAD) is characterized by severe chest, back, or abdominal pain, ripping or tearing in nature. However, some patients present with painless acute aortic dissection, which can lead to a delay in diagnosis and treatment. We utilized the International Registry on Acute Aortic Dissections (IRAD) database to study these patients. Methods: We analyzed 43 painless TBAAD patients enrolled in the database between January 1996 and July 2012. The differences in presentation, diagnostics, management, and outcome were compared with patients presenting with painful TBAAD. Results: Among the 1162 TBAAD patients enrolled in IRAD, 43 patients presented with painless TBAAD (3.7%). The mean age of patients with painless TBAAD was significantly higher than normal TBAAD patients (69.2 versus 63.3 years, P = 0.020). The presence of atherosclerosis (46.4% versus 30.1%, P = 0.022), diabetes (17.9% versus 7.5%; P = 0.018), and other aortic diseases (8.6% versus 2.3%, P= 0.051), such as prior aortic aneurysm (31% versus 18.8% P = 0.049) was more common in these patients. Median delay time between presentation and diagnosis was longer in painless patients (median 34.0 versus 19.0 hours; P = 0.006). Dissection of iatrogenic origin (19.5% versus 1.3%; P < 0.001) was significantly more frequent in the painless group. The in-hospital mortality was 18.6% in the painless group, compared with an in-hospital mortality of 9.9% in the control group (P = 0.063). Conclusion: Painless TBAAD is a relatively rare presentation (3.7%) of aortic dissection, and is often associated with a history of atherosclerosis, diabetes, prior aortic disease including aortic aneurysm, and an iatrogenic origin. We observed a trend for increased in-hospital mortality in painless TBAAD patients, which may be the result of a delay in diagnosis and management. Therefore, physicians should be aware of this relative rare presentation of

  18. Aortic stiffness determines diastolic blood flow reversal in the descending thoracic aorta: potential implication for retrograde embolic stroke in hypertension.

    PubMed

    Hashimoto, Junichiro; Ito, Sadayoshi

    2013-09-01

    Aortic stiffening often precedes cardiovascular diseases, including stroke, but the underlying pathophysiological mechanisms remain obscure. We hypothesized that such abnormalities could be attributable to altered central blood flow dynamics. In 296 patients with uncomplicated hypertension, Doppler velocity pulse waveforms were recorded at the proximal descending aorta and carotid artery to calculate the reverse/forward flow ratio and diastolic/systolic flow index, respectively. Tonometric waveforms were recorded on the radial artery to estimate aortic pressure and characteristic impedance (Z0) and to determine carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities. In all subjects, the aortic flow waveform was bidirectional, comprising systolic forward and diastolic reverse flows. The aortic reverse/forward flow ratio (35 ± 10%) was positively associated with parameters of aortic stiffness (including pulse wave velocity, Z0, and aortic/peripheral pulse wave velocity ratio), independent of age, body mass index, aortic diameter, and aortic pressure. The carotid flow waveform was unidirectional and bimodal with systolic and diastolic maximal peaks. There was a positive relationship between the carotid diastolic/systolic flow index (28 ± 9%) and aortic reverse/forward flow ratio, which remained significant after adjustment for aortic stiffness and other related parameters. The Bland-Altman plots showed a close time correspondence between aortic reverse and carotid diastolic flow peaks. In conclusion, aortic stiffness determines the extent of flow reversal from the descending aorta to the aortic arch, which contributes to the diastolic antegrade flow into the carotid artery. This hemodynamic relationship constitutes a potential mechanism linking increased aortic stiffness, altered flow dynamics, and increased stroke risk in hypertension.

  19. Endothelial nitric oxide synthase (eNOS) gene polymorphism in early term chronic allograft nephropathy.

    PubMed

    Yilmaz, E; Mir, S; Berdeli, A

    2009-12-01

    Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO. PMID:20005399

  20. 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

  1. Aortic valvular heart disease: Is there a place for angiotensin-converting-enzyme inhibitors?

    PubMed

    Elder, Douglas H J; McAlpine-Scott, Victoria; Choy, Anna Maria; Struthers, Allan D; Lang, Chim C

    2013-01-01

    Aortic valve disease (AVD) is the most common form of valvular heart disease in the western world. The only proven therapy for severe AVD is open aortic valve replacement, with trans-catheter aortic valve implantation emerging as a promising modality to treat severe aortic stenosis in a selected group of patients. AVD has a long asymptomatic phase with symptoms occurring late in the disease and once symptoms develop, prognosis is poor. There is a growing appreciation that aortic valvular heart disease incorporates a disease process that extends beyond the valve itself leading to an aortic valvular 'heart' disease. The renin-angiotensin system is known to modulate adverse left ventricular remodeling and myocardial fibrosis, which could be caused by increased load caused by the AVD. In this review, the authors explore evidence that suggest that drugs that target the renin-angiotensin system may have a potential therapeutic role in AVD.

  2. A shifting approach to management of the thoracic aorta in bicuspid aortic valve

    PubMed Central

    Opotowsky, Alexander R.; Perlstein, Todd; Landzberg, Michael J.; Colan, Steven D.; O’Gara, Patrick T.; Body, Simon C.; Ryan, Liam F.; Aranki, Sary; Singh, Michael N.

    2014-01-01

    Objectives The scientific understanding of aortic dilation associated with bicuspid aortic valve (BAV) has evolved during the past 2 decades, along with improvements in diagnostic technology and surgical management. We aimed to evaluate secular trends and predictors of thoracic aortic surgery among patients with BAV in the United States. Methods We used the 1998-2009 Nationwide Inpatient Sample, an administrative dataset representative of US hospital admissions, to identify hospitalizations for adults aged 18 years or more with BAV and aortic valve or thoracic aortic surgery. Covariates included age, gender, year, aortic dissection, endocarditis, thoracic aortic aneurysm, number of comorbidities, hospital teaching status and region, primary insurance, and concomitant coronary artery bypass surgery. Results Between 1998 and 2009, 48,736 ± 3555 patients with BAV underwent aortic valve repair or replacement and 1679 ± 120 patients with BAV underwent isolated thoracic aortic surgery. The overall number of surgeries increased more than 3-fold, from 4556 ± 571 in 1998/1999 to 14,960 ± 2107 in 2008/2009 (P < .0001). The proportion of aortic valve repair or replacement including concomitant thoracic aortic surgery increased from 12.8% ± 1.4% in 1998/1999 to 28.5% ± 1.6% in 2008/2009, which mirrored an increasing proportion of patients with a diagnosis of thoracic aortic aneurysm. Mortality was equivalent for patients undergoing aortic valve repair or replacement with thoracic aortic surgery and those undergoing isolated aortic valve repair or replacement (1.8% ± 0.3% vs 1.5% ± 0.2%; multivariable odds ratio, 1.02; 95% confidence interval, 0.67-1.57), with decreasing mortality over the study period (from 2.5% ± 0.6% in 1998/1999 to 1.5% ± 0.2% in 2008/2009; multivariable odds ratio per 2-year increment, 0.89; 95% confidence interval, 0.81-0.99; P = .03). Total charges for BAV surgical hospitalizations increased more than 7.5-fold from approximately $156 million in

  3. Intraoperative aortic dissection

    PubMed Central

    Singh, Ajmer; Mehta, Yatin

    2015-01-01

    Intraoperative aortic dissection is a rare but fatal complication of open heart surgery. By recognizing the population at risk and by using a gentle operative technique in such patients, the surgeon can usually avoid iatrogenic injury to the aorta. Intraoperative transesophageal echocardiography and epiaortic scanning are invaluable for prompt diagnosis and determination of the extent of the injury. Prevention lies in the strict control of blood pressure during cannulation/decannulation, construction of proximal anastomosis, or in avoiding manipulation of the aorta in high-risk patients. Immediate repair using interposition graft or Dacron patch graft is warranted to reduce the high mortality associated with this complication. PMID:26440240

  4. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation

    PubMed Central

    Wen, Jiaming; Grenz, Almut; Zhang, Yujin; Dai, Yingbo; Kellems, Rodney E.; Blackburn, Michael R.; Eltzschig, Holger K.; Xia, Yang

    2011-01-01

    Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5′-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A2B receptor (A2BR) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A2BR signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A2BR in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both P<0.05). Overall, using biochemical, cellular, genetic, and physiological approaches, our findings reveal that adenosine is a novel molecule signaling via A2BR activation, contributing to penile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.—Wen, J., Grenz, A., Zhang, Y., Dai, Y., Kellems, R. E., Blackburn, M. R., Eltzschig, H. K., Xia, Y. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation. PMID

  5. Thoracic endovascular aortic repair for blunt thoracic aortic injuries in complex aortic arch vessels anatomies.

    PubMed

    Piffaretti, Gabriele; Carrafiello, Gianpaolo; Ierardi, Anna Maria; Mariscalco, Giovanni; Macchi, Edoardo; Castelli, Patrizio; Tozzi, Matteo; Franchin, Marco

    2015-08-01

    The aim of this study is to report the use of thoracic endovascular aortic repair (TEVAR) in blunt thoracic aortic injuries (BTAIs) presenting with complex anatomies of the aortic arch vessels. Two patients were admitted to our hospital for the management of BTAI. Anomalies were as follow: aberrant right subclavian artery (n = 1) and right-sided aortic arch with 5 vessels anatomy variant (n = 1). TEVAR was accomplished using parallel graft with periscope configuration in the patient with the aberrant right subclavian artery. At 12-month follow-up, computed tomography angiographies confirmed the exclusion of the BTAI, the stability of the endograft, the resolution of the pseudoaneurysm, and the patency of the parallel endograft. Aortic arch vessels variants and anomalies are not rare, and should be recognized and studied precisely to plan the most appropriate operative treatment. TEVAR proved to be effective even in complex anatomies.

  6. Delayed surgery for type A aortic dissection caused by blunt trauma.

    PubMed

    Takahashi, Shinya; Uchida, Naomichi; Takasaki, Taiichi; Sueda, Taijiro

    2015-02-01

    We describe a rare case of delayed surgery for blunt ascending aortic injury. A 77-year-old man was injured in a traffic accident. He lost consciousness and suffered severe blunt trauma to the chest. Computed tomography showed multiple head and chest injuries and acute Stanford type A aortic dissection. The operation was postponed because he was hemodynamically stable and his risk of surgical death was increased due to his other injuries. Serial computed tomography showed growth of the aortic lesion, and aortic surgery was successfully performed 11 months after admission to the hospital. The postoperative course was uneventful.

  7. Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors

    PubMed Central

    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 Ca2+ 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. PMID:27630578

  8. 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. PMID:27630578

  9. Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors

    PubMed Central

    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 Ca2+ 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.

  10. Abdominal aortic grafting for spontaneous infrarenal abdominal aortic dissection.

    PubMed

    Iwasaki, Hiroto; Shibuya, Takashi; Shintani, Takashi; Uenaka, Hisazumi; Suehiro, Shigefumi; Satoh, Hisashi

    2010-02-01

    This case report concerns a 62-year-old woman with spontaneous infrarenal abdominal aortic dissection, which developed into claudication and rest pain in the lower extremity. Multi-row detector computed tomography showed the entry site of the abdominal aortic dissection at the second lumbar artery, while the reentry site was found intraoperatively at the median sacral artery, indicating that the false lumen had progressed and compressed the true lumen. A direct approach involving grafting appears to be an effective procedure for resolving mesenteric and lower extremity hypoperfusion due to aortic dissection with a dilated false channel, even during the acute period. PMID:19879731

  11. Transcatheter aortic valve implantation in bicuspid aortic valve stenosis.

    PubMed

    Perlman, Gidon Y; Blanke, Philipp; Webb, John G

    2016-09-18

    Bicuspid aortic stenosis (AS) is not rare in patients treated with transcatheter aortic valve implantation (TAVI). Bicuspid valves have unique anatomy which could affect the results of TAVI; however, multiple recent reports have shown that TAVI is safe and effective in this population. Paravalvular aortic regurgitation was initially found to be more frequent in bicuspid patients, but newer-generation devices have shown superior results in this respect. Higher rates of pacemaker implantation after TAVI in bicuspid AS do require further investigation. Current data suggest that bicuspid valves should not be a contraindication for TAVI, but future specific trials are needed to support this assertion. PMID:27640030

  12. 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

    SciTech Connect

    Park, Jung-Hyun; Lee, Sangmi; Cho, Du-Hyong; Park, Young Mi; Kang, Duk-Hee; Jo, Inho

    2013-07-12

    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 and 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. This

  13. Effect of abdominal aortic grafts on aortic stiffness and central hemodynamics.

    PubMed

    Lantelme, Pierre; Dzudie, Anastase; Milon, Hugues; Bricca, Giampiero; Legedz, Liliana; Chevalier, Jean-Michel; Feugier, Patrick

    2009-06-01

    Graft-prosthesis and stentgraft placements are effective modalities for treating abdominal aortic aneurysm, but related changes in arterial stiffness are not well established. The present study sought to assess aortic stiffness after aneurism repair by measuring pulse wave velocity (PWV). The graft-related variation of carotid-femoral PWV was compared with that of carotid-radial PWV, the latter being unaffected by vascular treatment. The secondary objective was to evaluate potential differences between graft-prosthesis and stentgraft in terms of aortic stiffness and augmentation index, a composite indicator integrating wave reflexion. Fifty patients were included (39 had a graft-prosthesis and 11 had a stentgraft). In the whole group and after a median postoperative follow-up of 47 days, carotid-femoral PWV increased by +1.0 m/s [-12.3, +10.3], while carotid-radial PWV slightly decreased by -0.3 m/s [-4.4; +3.5] (P = 0.001). The effect of the type of prosthesis on the PWV was not significant. Nevertheless, the augmentation index increased after stentgraft implantation (+4% [-10; +17]) and decreased after graft-prosthesis placement (-8.5% [-47; +17]) (P < 0.01). This difference was not explained by a heart rate or a treatment effect and was likely attributable to the prosthesis per se. This study demonstrates the impact of aortic grafts on aortic stiffness. Besides, it suggests that stentgraft increases reflected waves more than graft-prostheses. These changes of vascular properties may influence the outcomes after surgery. PMID:19342960

  14. Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

    PubMed Central

    Yap, Choon Hwai; Saikrishnan, Neelakantan; Tamilselvan, Gowthami

    2011-01-01

    Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. Although exact causes and mechanisms of AV calcification are unclear, previous studies suggest that mechanical forces play a role. Since calcium deposits occur almost exclusively on the aortic surfaces of AV leaflets, it has been hypothesized that adverse patterns of fluid shear stress on the aortic surface of AV leaflets promote calcification. The current study characterizes AV leaflet aortic surface fluid shear stresses using Laser Doppler velocimetry and an in vitro pulsatile flow loop. The valve model used was a native porcine valve mounted on a suturing ring and preserved using 0.15% glutaraldehyde solution. This valve model was inserted in a mounting chamber with sinus geometries, which is made of clear acrylic to provide optical access for measurements. To understand the effects of hemodynamics on fluid shear stress, shear stress was measured across a range of conditions: varying stroke volumes at the same heart rate and varying heart rates at the same stroke volume. Systolic shear stress magnitude was found to be much higher than diastolic shear stress magnitude due to the stronger flow in the sinuses during systole, reaching up to 20 dyn/cm2 at mid-systole. Upon increasing stroke volume, fluid shear stresses increased due to stronger sinus fluid motion. Upon increasing heart rate, fluid shear stresses decreased due to reduced systolic duration that restricted the formation of strong sinus flow. Significant changes in the shear stress waveform were observed at 90 beats/ min, most likely due to altered leaflet dynamics at this higher heart rate. Overall, this study represents the most well-resolved shear stress measurements to date across a range of conditions on the aortic side of the AV. The data presented can be used for further investigation to understand AV biological response to shear stresses. PMID:21416247

  15. Angiotensin II receptor blocker telmisartan attenuates aortic stiffening and remodelling in STZ-diabetic rats

    PubMed Central

    2014-01-01

    Background Prevention or attenuation of diabetic vascular complications includes anti-hypertensive treatment with renin-angiotensin system inhibitors on account of their protective effects beyond blood pressure reduction. The present study aimed to investigate the effects of telmisartan, an angiotensin II type 1 receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic remodelling in experimental type 1 diabetes in rats. Methods Diabetes was induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure-independent aortic pulse wave velocity (PWV) was measured under anaesthesia after intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples were collected for histomorphometrical analysis. Results Untreated diabetes imposed differential effects on aortic stiffening, as demonstrated by increased isobaric PWV over a range of high blood pressures, but not at lower blood pressures. This was associated with loss and disruption of elastin fibres and an increase in collagen fibres in the aortic media. Treatment with telmisartan decreased resting blood pressure, reduced aortic stiffness, and partially prevented the degradation of elastin network within the aortic wall. Conclusions Telmisartan improved the structural and functional indices of aortic stiffening induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the therapeutic approach to diabetic vascular complications. PMID:24920962

  16. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    PubMed

    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

  17. Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.

    PubMed

    Salvi, Erika; Kuznetsova, Tatiana; Thijs, Lutgarde; Lupoli, Sara; Stolarz-Skrzypek, Katarzyna; D'Avila, Francesca; Tikhonoff, Valerie; De Astis, Silvia; Barcella, Matteo; Seidlerová, Jitka; Benaglio, Paola; Malyutina, Sofia; Frau, Francesca; Velayutham, Dinesh; Benfante, Roberta; Zagato, Laura; Title, Alexandra; Braga, Daniele; Marek, Diana; Kawecka-Jaszcz, Kalina; Casiglia, Edoardo; Filipovsky, Jan; Nikitin, Yuri; Rivolta, Carlo; Manunta, Paolo; Beckmann, Jacques S; Barlassina, Cristina; Cusi, Daniele; Staessen, Jan A

    2013-11-01

    A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers (P≤0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8 mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes (P≥0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension.

  18. Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.

    PubMed

    Salvi, Erika; Kuznetsova, Tatiana; Thijs, Lutgarde; Lupoli, Sara; Stolarz-Skrzypek, Katarzyna; D'Avila, Francesca; Tikhonoff, Valerie; De Astis, Silvia; Barcella, Matteo; Seidlerová, Jitka; Benaglio, Paola; Malyutina, Sofia; Frau, Francesca; Velayutham, Dinesh; Benfante, Roberta; Zagato, Laura; Title, Alexandra; Braga, Daniele; Marek, Diana; Kawecka-Jaszcz, Kalina; Casiglia, Edoardo; Filipovsky, Jan; Nikitin, Yuri; Rivolta, Carlo; Manunta, Paolo; Beckmann, Jacques S; Barlassina, Cristina; Cusi, Daniele; Staessen, Jan A

    2013-11-01

    A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers (P≤0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8 mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes (P≥0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension. PMID:24019403

  19. Single Coronary Artery with Aortic Regurgitation

    SciTech Connect

    Katsetos, Manny C. Toce, Dale T.

    2003-11-15

    An isolated single coronary artery can be associated with normal life expectancy; however, patients are at an increased risk of sudden death. A case is reported of a 54-year-old man with several months of chest pressure with activity. On exercise Sestamibi stress testing, the patient developed a hypotensive response with no symptoms and minimal electrocardiographic changes. Nuclear scanning demonstrated reversible septal and lateral perfusion defects consistent with severe ischemia. Coronary angiography revealed a single coronary artery with the right coronary artery arising from the left main. There were high-grade stenotic lesions in the left anterior descending and circumflex arteries with only moderate atherosclerotic disease in the right coronary artery. An aortogram showed 2-3+ aortic regurgitation, with an ejection fraction of 45% on ventriculography. The patient underwent four-vessel revascularization and aortic valve replacement and did well postoperatively.

  20. Recurrent Gain-of-Function Mutation in PRKG1 Causes Thoracic Aortic Aneurysms and Acute Aortic Dissections

    PubMed Central

    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.

    2013-01-01

    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. PMID:23910461

  1. 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 Central

    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.

    2016-01-01

    Background The long-term outcomes of aortic valve sparing (AVS) root replacement in Marfan syndrome (MFS) patients remain uncertain. We sought 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). Methods At the time of this analysis, 788 patients with MFS were enrolled in the GenTAC Registry, of whom 288 have undergone aortic root replacement. Patients who have undergone AVS procedures were compared to those who have undergone aortic valve replacing (AVR) procedures. Results AVS root replacement was performed in 43.5% of MFS patients and the frequency of AVS increased over the past 5 years. AVS patients were younger at the time of surgery (31.0 vs. 36.3 years, p=0.006) and more likely to have had elective rather than emergency surgery compared to AVR patients. AVR patients were more likely to have had aortic valve dysfunction and aortic dissection as a primary indication for surgery. After mean follow-up of 6.2 (SD=3.6) years, none of the 87 AVS patients have required reoperation; in contrast, after mean follow up of 10.5 (SD=7.6) years, 11.5% of AVR patients have required aortic root reoperation. Aortic valve function has been durable with 95.8% of AVS patients with aortic insufficiency graded as mild or less. Conclusions AVS root replacement is performed commonly in the MFS population. The durability of the aortic repair and aortic valve function have been excellent to date. These results justify the continued use of the procedure in the elective setting. The GenTAC Registry will be a useful resource to assess the long-term durability of AVS root replacement in the future. PMID:25296451

  2. Total aortic repair: the new paradigm in the treatment of acute type A aortic dissection

    PubMed Central

    Perera, Nisal K.; Galvin, Sean D.

    2016-01-01

    The surgical management of acute type A aortic dissection (ATAAD) is in a period of rapid evolution. Understanding the complex physiology and anatomy of both acute and chronic dissection has been enhanced by the ready availability of state of the art imaging techniques. Technical advances in the intraoperative monitoring of organ perfusion, together with adjuncts to limit organ injury and increasing sophistication in open and endovascular surgery have led to a major reduction in both perioperative morbidity and mortality. In many centers, there has been a transition in mindset and surgical approach away from a purely central aortic operation focusing on the ascending aorta and a ‘live to fight another day’ philosophy. The current more global perspective recognizes the importance of aortic valve function, malperfusion, false lumen (FL) patency and the potential for future complex aneurysm development. The time is now right to transition into the next phase of sophistication in the management of ATAAD with the aim of achieving not only a safe acute operation, but to either entirely prevent chronic complications or to greatly simplify their management by the creation of an anatomical situation that facilitates future endovascular intervention in place of complex re-do surgery. We present our view on the evolution of surgery for ATAAD leading to our current technique of Branch First Arch replacement and Total Aortic Repair, which not only provides a safe immediate operation, but also offers the hope of a simplified future management if not a total cure for the pathology. PMID:27386409

  3. 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...

  4. 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...

  5. ENOS-G894T polymorphism is a risk factor for essential hypertension in China.

    PubMed

    Men, Chen; Tang, Kangting; Lin, Gang; Li, Jian; Zhan, Yiyang

    2011-06-01

    Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with coronary artery disease; however, associations between polymorphism (G894T) of the eNOS gene and essential hypertension remain unclear. This study was designed to investigate the association between a eNOS-G894T polymorphism and essential hypertension (EH). A total of 190 Chinese EH patients (EH group) and 94 healthy participants (control group) were included in the study. eNOS-G894T was determined using multi-polymerase chain reaction and polymorphisms in eNOS-G894T were genotyped using gene chip technology. Patients carrying eNOS GT + TT genotypes had a higher risk of EH than those carrying the GG genotype (OR = 2.82, 95% CI: 1.05-7.60, P = 0.033). The EH group showed a significantly higher frequency of the T-allele compared with controls (OR = 3.48, 95% CI: 1.34-9.07; P = 0.007). eNOS-894T was found to be significantly associated with EH in the dominant genetic model. Thus, the study demonstrated a significant and independent association between a eNOS-G894T polymorphism and EH in the Chinese patients. The study also showed that eNOS-G894T polymorphism is a risk factor for EH in Chinese patients. PMID:21793305

  6. Reoperative Aortic Root Replacement in Patients with Previous Aortic Root or Aortic Valve Procedures

    PubMed Central

    Chong, Byung Kwon; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won; Kim, Joon Bum

    2016-01-01

    Background Generalization of standardized surgical techniques to treat aortic valve (AV) and aortic root diseases has benefited large numbers of patients. As a consequence of the proliferation of patients receiving aortic root surgeries, surgeons are more frequently challenged by reoperative aortic root procedures. The aim of this study was to evaluate the outcomes of redo-aortic root replacement (ARR). Methods We retrospectively reviewed 66 patients (36 male; mean age, 44.5±9.5 years) who underwent redo-ARR following AV or aortic root procedures between April 1995 and June 2015. Results Emergency surgeries comprised 43.9% (n=29). Indications for the redo-ARR were aneurysm (n=12), pseudoaneurysm (n=1), or dissection (n=6) of the residual native aortic sinus in 19 patients (28.8%), native AV dysfunction in 8 patients (12.1%), structural dysfunction of an implanted bioprosthetic AV in 19 patients (28.8%), and infection of previously replaced AV or proximal aortic grafts in 30 patients (45.5%). There were 3 early deaths (4.5%). During follow-up (median, 54.65 months; quartile 1–3, 17.93 to 95.71 months), there were 14 late deaths (21.2%), and 9 valve-related complications including reoperation of the aortic root in 1 patient, infective endocarditis in 3 patients, and hemorrhagic events in 5 patients. Overall survival and event-free survival rates at 5 years were 81.5%±5.1% and 76.4%±5.4%, respectively. Conclusion Despite technical challenges and a high rate of emergency conditions in patients requiring redo-ARR, early and late outcomes were acceptable in these patients. PMID:27525233

  7. Endoanchor stenting for the repair of a Type I endoleak in the aortic arch following the endovascular repair of a Kommerrell's diverticulum.

    PubMed

    Menon, Rohan S; Muetterties, Corbin; Moser, George William; Wheatley, Grayson H

    2016-08-01

    As more challenging aortic arch anatomy is being treated using aortic stent-grafts, there is an increased risk for proximal Type I endoleaks at the proximal seal zone or subsequent graft migration. We report a case of an endoanchor-assisted thoracic endovascular aneurysm repair of a patient with an aberrant right subclavian artery (ARSA) and aortic arch aneurysm who developed a proximal Type I endoleak in the aortic arch which was subsequently treated with endoanchors. PMID:27349832

  8. Aortic dissection--an update.

    PubMed

    Mukherjee, Debabrata; Eagle, Kim A

    2005-06-01

    Acute aortic dissection is a medical emergency with high morbidity and mortality requiring emergent diagnosis and therapy. Rapid advances in noninvasive imaging technology have facilitated the early diagnosis of this condition and should be considered in the differential diagnosis of any patient with chest, back, or abdominal pain. Emergent surgery is the treatment for patients with type A dissection while optimal medical therapy is appropriate in patients with uncomplicated type B dissection. Adequate beta-blockade is the cornerstone of medical therapy. Patients who survive acute aortic dissection need long-term medical therapy with beta-blockers and statins and appropriate serial imaging follow-up. Future advances in this field include biomarkers in the early diagnosis of acute aortic dissection and presymptomatic diagnosis with genetic screening. Overall patients with aortic dissection are at high risk for an adverse outcome and need to be managed aggressively in hospital and long term with frequent follow-up. PMID:15973249

  9. eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

    PubMed

    McIlhenny, Stephen; Zhang, Ping; Tulenko, Thomas; Comeau, Jason; Fernandez, Sarah; Policha, Aleksandra; Ferroni, Matthew; Faul, Elizabeth; Bagameri, Gabor; Shapiro, Irving; DiMuzio, Paul

    2015-11-01

    This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications.

  10. Augmentation of platelet and endothelial cell eNOS activity decreases sepsis-related neutrophil-endothelial cell interactions.

    PubMed

    Khan, Raymond; Kirschenbaum, Linda A; LaRow, Catherine; Berna, Gioiamaria; Griffin, Kelly; Astiz, Mark E

    2010-03-01

    NO is an important mediator of microvascular patency and blood flow. The purpose of this study was to examine the role of enhanced eNOS activity in attenuating sepsis-induced neutrophil-endothelial cell interactions. Microslides coated with human umbilical vein endothelial cells were stimulated with plasma from patients with septic shock. Neutrophil and platelets from control subjects were also stimulated with plasma from patients in septic shock and perfused over stimulated endothelial cells. l-Arginine (LA) with and without NG-monomethyl l-arginine (LNMMA), a nonselective NOS inhibitor, and N-(3-(aminomethyl) benzyl acetamide) ethanimidamide dihydrochloride (1400W), a highly selective iNOS inhibitor, were added to the septic plasma. The number of neutrophils adherent to endothelial cells, neutrophil rolling velocity, and the number of neutrophil aggregates were determined. Cell activation and the formation of platelet-neutrophil aggregates were assessed by flow cytometry. Separate experiments were done with isolated platelets using platelet aggregometry. l-Arginine significantly decreased sepsis-related neutrophil adhesion and aggregation and increased rolling velocity. The addition of LNMMA to LA and cell suspensions reversed the effects of LA on these parameters, whereas the addition of 1400W had no effect on LA-related changes. Platelet-neutrophil aggregation, platelet aggregation, platelet activation, and neutrophil activation induced by septic plasma were also significantly decreased by LA. Again, the addition of LNMMA reversed the effects of LA on these parameters, whereas 1400W had no effect on LA-related changes. These data suggest that enhancement of platelet and endothelial cell eNOS activity decreases sepsis-induced neutrophil-endothelial cell interactions and may play a role in maintaining microvascular patency in septic shock.

  11. [New aspects in aortic valve disease].

    PubMed

    Tornos, P

    2001-01-01

    Renewed interest for aortic valve disease has evolved in recent years. Aortic valve replacement has become the second most frequent cause of cardiac surgery, following coronary bypass surgery. In addition, the etiologic and physiopathologic knowledge of this disorder has improved. In the present paper we analyze three aspects of the disease which are, at present, the subject of study and controversy: first, we discuss the possible relationship between degenerative aortic stenosis and atherosclerosis; second, the involvement of the aortic root in cases of bicuspid aortic valve; and third, the surgical indications in asymptomatic patients with either aortic stenosis or regurgitation.

  12. Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

    PubMed Central

    Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

    2009-01-01

    Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

  13. Molecular and Genetic Insights into Thoracic Aortic Dilation in Conotruncal Heart Defects

    PubMed Central

    Kay, W. Aaron

    2016-01-01

    Thoracic aortic dilation (AD) has commonly been described in conotruncal defects (CTDs), such as tetralogy of Fallot, double outlet right ventricle and transposition of the great arteries, and truncus arteriosus. Several theories for this have been devised, but fairly recent data indicate that there is likely an underlying histologic abnormality, similar to that seen in Marfan and other connective tissue disease. The majority of aortic dissection in the general population occurs after the age of 45 years, and there have been very few case reports of aortic dissection in CTD. Given advances in cardiac surgery and increasing survival over the past several decades, there has been rising concern that, as patients who have survived surgical correction of these defects age, there may be increased morbidity and mortality due to aortic dissection and aortic regurgitation. This review discusses the most recent developments in research into AD in CTD, including associated genetic mutations. PMID:27376074

  14. Immersed boundary-finite element model of fluid-structure interaction in the aortic root

    NASA Astrophysics Data System (ADS)

    Flamini, Vittoria; DeAnda, Abe; Griffith, Boyce E.

    2016-04-01

    It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe a fluid-structure interaction model of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employs a version of Peskin's immersed boundary (IB) method with a finite element description of the structural elasticity. As in earlier work, we use a fiber-based model of the valve leaflets, but this study extends earlier IB models of the aortic root by employing an incompressible hyperelastic model of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backward displacement method that determines the unloaded configuration of the root model. Our model yields realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations indicate that although the detailed leaflet and root kinematics show some grid sensitivity, our IB model of the aortic root nonetheless produces essentially grid-converged flow rates and pressures at practical grid spacings for the high Reynolds number flows of the aortic root. These results thereby clarify minimum grid resolutions required by such models when used as stand-alone models of the aortic valve as well as when used to provide models of the outflow valves in models of left-ventricular fluid dynamics.

  15. Phonocardiographic Assessment of Hemodynamic Response to Balloon Aortic Valvuloplasty

    PubMed Central

    Bush, Howard S.; Ferguson, James J.

    1990-01-01

    The time to systolic murmur peak is a clinical index that is useful in assessing the severity of valvular aortic stenosis. To determine whether phonocardiography could be used to detect a change in the timing of the murmur and thus to measure hemodynamic improvements in elderly balloon aortic valvuloplasty patients, we retrospectively reviewed phonocardiographic tracings of 18 patients taken before and after the procedure. Ten men and 8 women were included in the study; the mean age was 80.7 ± 11.2 years (range, 64 to 90). Phonocardiographic signals were digitized, and the R-wave to murmur peak interval (R-MP) was measured. In 11 patients, the R-MP decreased (mean decrease, 16% ± 11%): of these, 10 had a significant (> 25%) decrease in mean gradient; 10 had a significant (> 25%) decrease in peak-to-peak gradient; and the average increase in aortic valve area was 38%. Seven patients had an increase in R-MP (mean increase, 10% ± 9%): of these, 6 had a decrease in mean gradient of less than 25%; 6 had a decrease in peak-to-peak gradient of less than 25%; and the average increase in aortic valve area was 21%. Pre- and post-balloon aortic valvuloplasty heart rates were not significantly different (71 ± 8 beats/min versus 73 ± 5 beats/min). In this study, hemodynamic improvements after valvuloplasty were manifested by a reduction in the R-MP interval. We conclude that phonocardiography may be a practical, noninvasive method of assessing the hemodynamic response to balloon aortic valvuloplasty. (Texas Heart Institute Journal 1990;17:42-7) PMID:15227188

  16. Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra

    ClinicalTrials.gov

    2016-03-09

    Aortic Valve Insufficiency; Aortic Valve Regurgitation; Aortic Valve Stenosis; Aortic Valve Incompetence; Mitral Valve Insufficiency; Mitral Valve Regurgitation; Mitral Valve Stenosis; Mitral Valve Incompetence

  17. Computed tomography for planning transcatheter aortic valve replacement.

    PubMed

    Apfaltrer, Paul; Henzler, Thomas; Blanke, Phillip; Krazinski, Aleksander W; Silverman, Justin R; Schoepf, U Joseph

    2013-07-01

    Transcatheter aortic valve replacement (TAVR) is rapidly becoming a widely used alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis at high surgical risk. In these patients, TAVR has been associated with markedly improved survival and relief from symptoms. Despite a very-high risk patient profile, recent multicenter registries have confirmed the safety and efficacy of this procedure. Moreover, the randomized, controlled PARTNER (Placement of AoRTic TraNscathetER Valves) trial has confirmed both the superiority of TAVR over medical treatment in patients not considered to be candidates for standard SAVR and the noninferiority of TAVR compared with SAVR in high-risk patients. The TAVR procedure requires a comprehensive preinterventional diagnostic workup. Above all, detailed information on the anatomy of the aortic annulus (AA) and the relation of the AA to the coronary arteries is essential to avoid complications. So far, no imaging reference standard for AA sizing has been established. Echocardiography, catheter angiography, and computed tomography angiography are widely and often complementarily used imaging techniques for this purpose. Compared with 2-dimensional imaging techniques, computed tomography (CT) has been proven to provide comprehensive information on AA anatomy and geometry, supporting appropriate patient selection and prosthesis sizing. In addition, CT is gaining an increasing role in evaluating the vascular access route before the procedure. This article describes the rapidly emerging role of CT in the context of pre-TAVR assessment.

  18. Aortic cusp extension valvuloplasty: repair with an extracellular patch

    PubMed Central

    Pawlak, Szymon; Śliwka, Joanna; Urlik, Maciej; Maruszewski, Marcin; Kukulski, Tomasz; Nożyński, Jerzy; Zembala, Marian

    2015-01-01

    Introduction The proportion of valve repair procedures is increasing in experienced centers. The aim of the study was to assess the clinical and echocardiographic outcomes after aortic valve reconstruction with a novel surgical technique. Material and methods The study group consisted of 30 patients (23 male and 7 female) at a mean age of 35 ± 14 years. In patients with aortic root aneurysm the reimplantation or Florida sleeve technique was used. A sub-commissural annuloplasty, plication of the free edge of the cusp, shaving, and commissurotomy were performed. At this stage of surgery aortic repair was then attempted by cusp extension. Since 2013 the strips have been tailored from extracellular matrix. Results The mean aortic cross-clamp time was 90 ± 32 min. The mean cardiopulmonary bypass time was 126 ± 38 min. There was no in-hospital death. Re-exploration for bleeding was required in 1 patient. During follow-up, 1 patient needed reoperation at 1 year due to endocarditis. All patients remained alive in New York Heart Association (NYHA) functional class I. The echocardiographic findings remained unchanged in all cases during follow-up. Conclusions Our modification of aortic valve repair results in a good outcome. PMID:26855646

  19. Evaluation of regional aortic distensibility using color kinesis.

    PubMed

    Kato, Yoshimasa; Kotoh, Keiju; Yamashita, Akio; Furuta, Hidetoshi; Shimazu, Chikasi; Misaki, Takurou

    2003-01-01

    Regional aortic stiffness cannot be evaluated by conventional methods. Regional aortic wall velocity during systole in the descending aorta was evaluated by using transesophageal echocardiography with color kinesis. The authors defined regional aortic distensibility (RAD) by considering pulse pressure, with RAD (microm/s/mm Hg) = (regional aortic wall velocity)/(pulse pressure). RAD was evaluated in 38 patients who had coronary artery disease (CAD) and 10 who did not. RAD decreased depending on aging (partial regression coefficient was -5.39 x 10(-1), p<0.001), and RAD was lower in the CAD group than that in the no-CAD group (p<0.05). In the CAD group, 19 patients had a single fixed plaque (4 calcified and 15 noncalcified plaques). RAD in the calcified plaque was lower than that in the noncalcified plaque (p<0.01), and RAD was lower in the noncalcified plaque than that in the no-plaque region (p<0.05). In noncalcified plaques, the relation between RAD and maximum intimal thickness had a significant correlation, r=0.7, p<0.001. The residual of RAD from the regression line was significantly larger in the calcified plaque than that in the noncalcified plaque (p<0.001). In conclusion, RAD can express increasing regional aortic wall stiffness brought about by arteriosclerosis quantitatively. Color kinesis provides information on characteristic difference between calcified and noncalcified plaque.

  20. Ascending Aortic Slide for Interrupted Aortic Arch Repair.

    PubMed

    Urencio, Miguel; Dodge-Khatami, Ali; Greenleaf, Chris E; Aru, Giorgio; Salazar, Jorge D

    2016-09-01

    For repair of interrupted aortic arch, unfavorable anatomy challenges a tension-free anastomosis. We describe a useful alternative surgical technique used in five neonates/infants, involving splitting the ascending aorta from the sinotubular junction to the arch origin, leftward and posterior "sliding" of the flap with anastomosis to the distal arch creating a native tissue bridge, and reconstruction with a patch. With wide interruption gaps between proximal and distal aortic portions, the ascending aortic slide is a safe and reproducible technique, providing a tension-free native tissue bridge with potential for growth, and a scaffold for patch augmentation in biventricular hearts, or for Norwood stage I in univentricular palliation. PMID:27587504

  1. Surgical Repair of Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic Repair

    PubMed Central

    Kim, Chang-Young; Kim, Yeon Soo; Ryoo, Ji Yoon

    2014-01-01

    It is expected that the stent graft will become an alternative method for treating aortic diseases or reducing the extent of surgery; therefore, thoracic endovascular aortic repair has widened its indications. However, it can have rare but serious complications such as paraplegia and retrograde type A aortic dissection. Here, we report a surgical repair of retrograde type A aortic dissection that was performed after thoracic endovascular aortic repair. PMID:24570865

  2. Abdominal aortic feminism.

    PubMed

    Mortimer, Alice Emily

    2014-11-14

    A 79-year-old woman presented to a private medical practice 2 years previously for an elective ultrasound screening scan. This imaging provided the evidence for a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a number of recognised risk factors for an AAA, her general practitioner at the time did not follow the guidance set out by the private medical professional, that is, to refer the patient to a vascular specialist to be entered into a surveillance programme and surgically evaluated. The patient became symptomatic with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6 cm leaking AAA. She consented for an emergency open AAA repair within a few hours of being admitted to hospital, despite the 50% perioperative mortality risk. The patient spent 4 days in intensive care where she recovered well. She was discharged after a 12 day hospital stay but unfortunately passed away shortly after her discharge from a previously undiagnosed gastric cancer.

  3. Open aortic surgery after thoracic endovascular aortic repair.

    PubMed

    Coselli, Joseph S; Spiliotopoulos, Konstantinos; Preventza, Ourania; de la Cruz, Kim I; Amarasekara, Hiruni; Green, Susan Y

    2016-08-01

    In the last decade, thoracic endovascular aortic aneurysm repair (TEVAR) has emerged as an appealing alternative to the traditional open aortic aneurysm repair. This is largely due to generally improved early outcomes associated with TEVAR, including lower perioperative mortality and morbidity. However, it is relatively common for patients who undergo TEVAR to need a secondary intervention. In select circumstances, these secondary interventions are performed as an open procedure. Although it is difficult to assess the rate of open repairs after TEVAR, the rates in large series of TEVAR cases (>300) have ranged from 0.4 to 7.9 %. Major complications of TEVAR that typically necessitates open distal aortic repair (i.e., repair of the descending thoracic or thoracoabdominal aorta) include endoleak (especially type I), aortic fistula, endograft infection, device collapse or migration, and continued expansion of the aneurysm sac. Conversion to open repair of the distal aorta may be either elective (as for many endoleaks) or emergent (as for rupture, retrograde complicated dissection, malperfusion, and endograft infection). In addition, in select patients (e.g., those with a chronic aortic dissection), unrepaired sections of the aorta may progressively dilate, resulting in the need for multiple distal aortic repairs. Open repairs after TEVAR can be broadly classified as full extraction, partial extraction, or full salvage of the stent-graft. Although full and partial stent-graft extraction imply failure of TEVAR, such failure is generally absent in cases where the stent-graft can be fully salvaged. We review the literature regarding open repair after TEVAR and highlight operative strategies.

  4. Minimal traumatic aortic injuries: meaning and natural history.

    PubMed

    Mosquera, Victor X; Marini, Milagros; Gulías, Daniel; Cao, Ignacio; Muñiz, Javier; Herrera-Noreña, José Manuel; López-Pérez, José Manuel; Cuenca, José Joaquin

    2012-06-01

    OBJECTIVE Minimal aortic injuries (MAIs) are being recognized more frequently due to the increasing use of high-resolution diagnostic techniques. The objective of this case series review was to report the clinical and radiological characteristics and outcomes of a series of patients with MAI. METHODS From January 2000 to December 2011, 54 major blunt trauma patients were admitted to our institution with traumatic aortic injuries. Nine of them presented with MAI, whereas the remaining 45 patients suffered a significant aortic injury (SAI). RESULTS MAIs accounted for 17% of the overall traumatic aortic injuries in our series. Major trauma patients with MAI and SAI were similar regarding the presence of severe associated non-aortic injuries and the expected mortality calculated by injury severity score, revised trauma score and trauma injury severity score. There were no statistically significant differences in in-hospital mortality between MAI (22.2%) and SAI (30.2%). No death in the MAI group was aortic related, whereas five deaths in the SAI group were caused by an aortic complication. The survival of MAI patients was 77.8% at 1 and 5 years. There was no late mortality among MAI patients. The survival of SAI patients was 69.7% at 1 year and 63.6% at 5 and 10 years. None of the seven surviving patients with MAI presented a progression of the aortic injury. In six patients, the intimal tear completely healed in imaging controls, whereas one patient developed a small saccular pseudoaneurysm. CONCLUSIONS Blunt traumas presenting MAI are as severe as traumas that associate SAI and present similar in-hospital mortality. In contrast to SAI traumas, in-hospital mortality due to MAI is not usually related to the aortic injury, so these injuries are more amenable to a conservative management. It is mandatory to perform a close imaging surveillance to detect early any potential adverse evolution of an MAI. Nevertheless, a balance must be struck between a close serial imaging

  5. Association between abdominal aortic plaque and coronary artery disease

    PubMed Central

    Li, Wei; Luo, Songyuan; Luo, Jianfang; Liu, Yuan; Huang, Wenhui; Chen, Jiyan

    2016-01-01

    Objective Currently, the association between abdominal aortic plaques and coronary artery disease (CAD) has not yet been clarified clearly. The purpose of this study was to determine the prevalence of abdominal aortic plaques by ultrasound imaging and to explore its association with CAD in patients undergoing coronary angiography. Methods Between October 2014 and June 2015, a prospective study was conducted in the Department of Cardiology at Guangdong General Hospital, Guangzhou, People’s Republic of China. Ultrasound scanning of the abdominal aortas was performed in 1,667 consecutive patients undergoing coronary angiography. Clinical characteristics and coronary profile were collected from the patients. Results Of the 1,667 study patients (male, 68.9%; mean age, 63±11 years) undergoing coronary angiography, 1,268 had CAD. Compared with 399 patients without CAD, 1,268 patients with CAD had higher prevalence of abdominal aortic plaques (37.3% vs 17%, P<0.001). In multivariate analysis, abdominal aortic plaques served as independent factors associated with the presence of CAD (odds ratio =2.08; 95% confidence interval =1.50–2.90; P<0.001). Of the 1,268 patients with CAD, the prevalence of abdominal aortic plaques was 27.0% (98/363) in patients with one-vessel disease, 35.0% (107/306) in patients with two-vessel disease, and 44.7% (268/599) in patients with three-vessel disease. Stepwise increases in the prevalence of abdominal aortic plaque was found depending on the number of stenotic coronary vessels (P<0.001; P-value for trend <0.001). In an ordinal logistic regression model, abdominal aortic plaques served as independent factors associated with the severity of CAD according to the number of stenotic coronary vessels (P<0.001). Conclusion The prevalence of abdominal aortic plaques was higher in patients with CAD than in those without CAD. Abdominal aortic plaque was an independent factor associated with the presence and severity of CAD. PMID:27279740

  6. [The usefulness of intravascular echography during the percutaneous dilatation of aortic coarctation].

    PubMed

    Goicolea, F J; Macaya, C; Iñíguez, A; Alfonso, F; Hernández Antolín, R; Vila i Costa, I; Zamorano, J; Egocheaga, I; Zarco, P

    1992-01-01

    An intravascular ultrasound study was performed in a patient, to assess the anatomy of aortic coarctation and the results obtained after percutaneous dilation with a balloon catheter. Intravascular ultrasound imaging provides important additional information, not obtainable with other diagnostic procedures, regarding aortic wall structure and thickness. After balloon dilation, aortic disruption was clearly observed, accounting, together with the stretching of the outer layers of the aortic wall, for the increase in aortic luminal area. Intravascular ultrasound permitted also the accurate assessment of the improvement obtained. Intravascular imaging was clearly superior not only to conventional angiography, but also to transesophageal echocardiography in detecting the mechanism of dilation. We conclude that ultravascular ultrasound, with the additional information that it provides, may help in the selection of patients for percutaneous dilation of the coarctation as well as contributing to the identification of the mechanism of dilation.

  7. Multiple endovascular aortic aneurysm repair graft failures and re-interventions over 15 years

    PubMed Central

    Belchos, Jessica; Wheatcroft, Mark; Moloney, Tony

    2015-01-01

    Re-intervention on abdominal aortic aneurysm treated by endovascular aortic aneurysm repair for complications such as endoleak, graft migration, and graft failure is relatively common. However, re-do endovascular aortic aneurysm repair can be complex, as the failed graft still resides within the vessel. In addition, some re-do endovascular aortic aneurysm repairs call for an advanced custom graft, which can further increase the complexity and technical skill required. We describe a case of a 15-year-old endovascular aortic aneurysm repair originally implanted in a 71-year-old man, followed by three separate complications requiring intervention. We describe important procedural decisions taken into consideration when presented with failure of an older graft. PMID:27489701

  8. Sotalol for the protection of turkeys from the development of β-aminopropionitrile-induced aortic ruptures

    PubMed Central

    Simpson, Charles F.

    1972-01-01

    1. The influence of feeding 2 levels of sotalol on the incidence of β-aminopropionitrile (BAPN)-induced aortic ruptures of immature turkeys was determined. 2. Four of 22 turkeys fed 0·12% sotalol and 0·07% BAPN died of aortic ruptures, but 6 of 21 turkeys fed only BAPN died of the syndrome. 3. Blood pressure, heart rate, aortic tensile strength, and aortic structure as seen by light- and electron-microscope were similar in turkeys fed BAPN alone or both BAPN and 0·12% sotalol concurrently. 4. In a second experiment, 13 of 24 turkeys fed 0·7% BAPN alone died of aortic ruptures, but only 2 of 24 turkeys fed BAPN and 0·2% sotalol concurrently died of the disease. 5. Aortic tensile strength was lower, heart rate was faster, alterations of aortic elastic fibres as seen by light- and electron-microscope were more severe, and aortic salt soluble collagen with a higher amino acid content was increased in turkeys fed only BAPN, as compared to turkeys fed both BAPN and 0·2% sotalol. PMID:4561180

  9. GenTAC Registry Report: Gender Differences Among Individuals with Genetically-Triggered Thoracic Aortic Aneurysm and Dissection

    PubMed Central

    Holmes, Kathryn W.; Maslen, Cheryl L.; Kindem, Mark; Kroner, Barbara L.; Song, Howard K.; Ravekes, William; Dietz, H.C.; Weinsaft, Jonathan W.; Roman, Mary J.; Devereux, Richard B.; Pyeritz, Reed E.; Bavaria, Joseph; Milewski, Karianna; Milewicz, Dianna; LeMaire, Scott A.; Hendershot, Tabitha; Eagle, Kim A.; Tolunay, H. Eser; Desvigne-Nickens, Patrice; Silberbach, Michael

    2013-01-01

    Previous data suggest women are at increased risk of death from aortic dissection. Therefore, we analyzed data from the GenTAC registry, the NIH-sponsored program that collects information about individuals with genetically-triggered thoracic aortic aneurysms and cardiovascular conditions. We performed cross-sectional analyses in adults with Marfan syndrome (MFS), familial thoracic aortic aneurysm or dissection (FTAAD), bicuspid aortic valve (BAV) with thoracic aortic aneurysm or dissection, and subjects under 50 years of age with thoracic aortic aneurysm or dissection (TAAD<50y). Women comprised 32% of 1449 subjects and were 21% of subjects with BAV, 34% with FTAAD, 22% with TAAD <50y, and 47% with MFS. Thoracic aortic dissections occurred with equal gender frequency yet women with BAV had more extensive dissections. Aortic size was smaller in women but was similar after controlling for BSA. Age at operation for aortic valve dysfunction, aneurysm or dissection did not differ by gender. Multivariate analysis (adjusting for age, BSA, hypertension, study site, diabetes, and subgroup diagnoses) showed that women had fewer total aortic surgeries (OR= 0.65, p < 0.01) and were less likely to receive angiotensin converting enzyme inhibitors (ACEi) (OR=0.68, p < 0.05). As in BAV, other genetically-triggered aortic diseases such as FTAAD and TAAD<50 are more common in males. In women, decreased prevalence of aortic operations and less treatment with ACEi may be due to their smaller absolute aortic diameters. Longitudinal studies are needed to determine if women are at higher risk for adverse events. PMID:23444191

  10. Transcatheter Aortic Valve Replacement: a Kidney’s Perspective

    PubMed Central

    Cheungpasitporn, Wisit; Thongprayoon, Charat; Kashani, Kianoush

    2016-01-01

    Transcatheter aortic valve replacement (TAVR) has now emerged as a viable treatment option for high-risk patients with severe aortic stenosis (AS) who are not suitable candidates for surgical aortic valve replacement (SAVR). Despite encouraging published outcomes, acute kidney injury (AKI) is common and lowers the survival of patients after TAVR. The pathogenesis of AKI after TAVR is multifactorial including TAVR specific factors such as the use of contrast agents, hypotension during rapid pacing, and embolization; preventive measures may include pre-procedural hydration, limitation of contrast dye exposure, and avoidance of intraprocedural hypotension. In recent years, the number of TAVR performed worldwide has been increasing, as well as published data on renal perspectives of TAVR including AKI, chronic kidney disease, end-stage kidney disease, and kidney transplantation. This review aims to present the current literature on the nephrology aspects of TAVR, ultimately to improve the patients’ quality of care and outcomes. PMID:27069960

  11. Type A aortic dissection presenting as superior vena cava syndrome.

    PubMed

    Raja, Faisal S; Islam, Ali; Khan, Mustafa; Abbasi, Iram

    2013-01-01

    A 51-year-old man presented with a 5-day history of progressive facial swelling, sensation of head fullness, increasing shortness of breath and paroxysmal nocturnal dyspnea. He denied chest pain, syncope or presyncope. Past medical history included mechanical aortic valve replacement 7 years prior and atrial fibrillation treated with warfarin. A clinical diagnosis of acute superior vena cava (SVC) syndrome was made. Portable chest radiograph showed a widened superior mediastinum. Computed tomography scan of the thorax demonstrated a large type A aortic dissection almost completely effacing the SVC. Acute type A aortic dissection (AD) is an emergency requiring prompt diagnosis and treatment. Patients typically present with acute onset of chest and/or back pain, classically described as "ripping" or "tearing." SVC syndrome is rarely, if ever, mentioned as a presentation, as it is usually due to more chronic conditions. This case illustrates a rare incidence of type A AD actually presenting as SVC syndrome.

  12. Aortic elastic properties in athletes using anabolic-androgenic steroids.

    PubMed

    Kasikcioglu, Erdem; Oflaz, Huseyin; Arslan, Armagan; Topcu, Berrin; Kasikcioglu, Hulya A; Umman, Berrin; Bugra, Zehra; Kayserilioglu, Abidin

    2007-01-01

    The use of anabolic-androgenic steroids (AAS) has been linked to acute cardiovascular events in athletes. The purpose of the present study was to investigate the aortic elastic properties in athletes who had been self-administering AAS compared with a group of athletes not using these drugs. Fourteen male bodybuilders using AAS and 27 male wrestlers (non-users) volunteered to the study. All subjects were placed in a mild recumbent position and the ascending aorta was recorded in the two-dimensional guided M-mode tracings. Although the aortic distensibility was found to be reduced in user athletes (2.1+/-1.1 vs. 3.8+/-1.4 cm(2) dyn(-1) 10(-6), p=0.01; 9.3+/-3.7 vs. 5.9+/-2.5, p=0.003, respectively). The results of this study indicate that aortic stiffness is increasing in athletes using AAS.

  13. Contribution of eNOS variants to the genetic susceptibility of coronary artery disease in a Tunisian population.

    PubMed

    Ben Ali, Marwa; Messaoudi, Safia; Ezzine, Houda; Mahjoub, Touhami

    2015-04-01

    Nitric oxide (NO), produced by the enzyme endothelial nitric oxide synthase (eNOS), has critical roles in the regulation of vascular homeostasis and prevention of atherogenesis by inhibiting leukocytes, platelet activation, and smooth muscle cell proliferation. There is strong experimental and clinical evidence that abnormalities in eNOS availability play an important role in the pathophysiology of coronary artery disease (CAD). Controversial results regarding the association of eNOS gene polymorphisms with CAD have been reported. The aim of this study is to investigate the relationship of the 894G>T (rs1799983) and 4a/4b (rs61722009) polymorphisms of the eNOS gene with the presence of CAD in the Tunisian population. A total of 332 patients with CAD and 368 controls were included in this study. The 894G>T (rs1799983) single-nucleotide polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and 4a/4b (rs61722009) polymorphism just by polymerase chain reaction (PCR). eNOS rs1799983 was significantly associated with CAD under the additive, dominant, but not recessive, models (additive model OR: 2.81; 95% CI [2.05-3.85]; p<0.001, dominant model OR: 2.84; 95% CI [2.09-3.86]; p<0.001, and recessive models p=0.09). This remained significant after adjustment for age, gender, diabetes, smoking, and hypertension. In contrast to eNOS rs1799983, eNOS rs61722009 was not associated with CAD under any of the genetic models tested. These findings suggest that the G894T (rs1799983) polymorphism of the eNOS gene was associated with CAD in Tunisian patients. PMID:25748584

  14. Aortic regurgitation caused by rupture of the abnormal fibrous band between the aortic valve and aortic wall.

    PubMed

    Minami, Hiroya; Asada, Tatsuro; Gan, Kunio; Yamada, Akitoshi; Sato, Masanobu

    2011-07-01

    This report documents the sudden onset of aortic regurgitation (AR) by an exceptional cause. A 68-year-old woman suddenly experienced general fatigue, and AR was diagnosed. One year later, we performed aortic valve replacement. At surgery, three aortic cusps with a larger noncoronary cusp had prolapsed along with a free-floating fibrous band that had previously anchored the cusp to the aortic wall. Its rupture had induced the sudden onset of AR. There was no sign of infectious endocarditis. We performed successful aortic valve replacement. PMID:21751110

  15. An artificial compression method for ENO schemes: The slope modification method

    NASA Technical Reports Server (NTRS)

    Yang, Huanan

    1988-01-01

    A simple and effective method of artificial compression is introduced. This method is based on a modification of the slopes of the ENO (essentially nonoscillatory) reconstruction and, with the help of suitable chosen parameters, greatly improves the resolution of the contact discontinuities. Numerical examples are provided to test the performance of the method and to give some suggestions as to the choice of the parameters.

  16. 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

    2016-07-01

    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. PMID:27255604

  17. Polymorphic variations in manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) genes contribute to the development of type 2 diabetes mellitus in the Chinese Han population.

    PubMed

    Li, J Y; Tao, F; Wu, X X; Tan, Y Z; He, L; Lu, H

    2015-01-01

    Impaired antioxidant defense increases the oxidative stress and contributes to the development of type 2 diabetes mellitus (T2DM). MnSOD and eNOS are important antioxidant enzymes. This aim of this study was to verify the association of MnSOD and eNOS tagSNPs with T2DM in a Chinese Han population. Four tagSNPs of MnSOD and eight tagSNPs of eNOS were detected using TaqMan technology in 1272 healthy controls and 1234 T2DM patients. All study participants were unrelated members of the Han ethnic group in China. In this study, the frequency of the rs4880 MnSOD single nucleotide polymorphisms (SNP) genotype differed significantly between T2DM patients and controls [allele: P = 0.03, genotype: P = 0.04, odd's ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07-1.49]. The A-T haplotype and G-T haplotype remained significant in T2DM after Bonferroni correction (P = 1.58 x 10(-6) and 8.00 x 10(-4), respectively) with a global p-value of 7.25 x 10(-8). The rs1799983 and rs891512 SNPs of eNOS differed significantly between T2DM patients and controls [rs1799983: corrected allele: P = 2.10 x 10(-3), corrected genotype: P = 6.30 x 10(-3), OR = 1.43 (95%CI = 1.18-1.73); rs891512, corrected allele: P = 3.50 x 10(-3), corrected genotype: P = 9.10 x 10(-3), OR = 1.70 (95%CI = 1.26-2.30)]. Following Bonferroni correction, none of the haplotypes of eNOS were significant in T2DM. These results indicate that common variants in MnSOD and eNOS increased the risk of T2DM in the Chinese Han population. PMID:26505452

  18. Polymorphic variations in manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) genes contribute to the development of type 2 diabetes mellitus in the Chinese Han population.

    PubMed

    Li, J Y; Tao, F; Wu, X X; Tan, Y Z; He, L; Lu, H

    2015-10-21

    Impaired antioxidant defense increases the oxidative stress and contributes to the development of type 2 diabetes mellitus (T2DM). MnSOD and eNOS are important antioxidant enzymes. This aim of this study was to verify the association of MnSOD and eNOS tagSNPs with T2DM in a Chinese Han population. Four tagSNPs of MnSOD and eight tagSNPs of eNOS were detected using TaqMan technology in 1272 healthy controls and 1234 T2DM patients. All study participants were unrelated members of the Han ethnic group in China. In this study, the frequency of the rs4880 MnSOD single nucleotide polymorphisms (SNP) genotype differed significantly between T2DM patients and controls [allele: P = 0.03, genotype: P = 0.04, odd's ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07-1.49]. The A-T haplotype and G-T haplotype remained significant in T2DM after Bonferroni correction (P = 1.58 x 10(-6) and 8.00 x 10(-4), respectively) with a global p-value of 7.25 x 10(-8). The rs1799983 and rs891512 SNPs of eNOS differed significantly between T2DM patients and controls [rs1799983: corrected allele: P = 2.10 x 10(-3), corrected genotype: P = 6.30 x 10(-3), OR = 1.43 (95%CI = 1.18-1.73); rs891512, corrected allele: P = 3.50 x 10(-3), corrected genotype: P = 9.10 x 10(-3), OR = 1.70 (95%CI = 1.26-2.30)]. Following Bonferroni correction, none of the haplotypes of eNOS were significant in T2DM. These results indicate that common variants in MnSOD and eNOS increased the risk of T2DM in the Chinese Han population.

  19. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    PubMed

    Tabata, Minoru

    2016-03-01

    Minimally invasive aortic valve replacement (MIAVR) is defined as aortic valve replacement avoiding full sternotomy. Common approaches include a partial sternotomy right thoracotomy, and a parasternal approach. MIAVR has been shown to have advantages over conventional AVR such as shorter length of stay and smaller amount of blood transfusion and better cosmesis. However, it is also known to have disadvantages such as longer cardiopulmonary bypass and aortic cross-clamp times and potential complications related to peripheral cannulation. Appropriate patient selection is very important. Since the procedure is more complex than conventional AVR, more intensive teamwork in the operating room is essential. Additionally, a team approach during postoperative management is critical to maximize the benefits of MIAVR.

  20. Pseudoaneurysm of the aortic arch

    PubMed Central

    Lu, Yuan-Qiang; Yao, Feng; Shang, An-Dong; Pan, Jian

    2016-01-01

    Abstract Background: Pseudoaneurysm of the aortic arch is uncommonly associated with cancer, and is extremely rare in pulmonary cancer. Here, we report an unusual and successfully treated case of aortic arch pseudoaneurysm in a male patient with lung squamous cell carcinoma. Methods: A 64-year-old male patient was admitted to the Emergency Department, presenting with massive hemoptysis (>500 mL blood during the 12 hours prior to treatment). The diagnosis of aortic arch pseudoaneurysm was confirmed after inspection of computed tomographic angiography and three-dimensional reconstruction. We processed the immediate endovascular stent-grafting for this patient. Results: This patient recovered with no filling or enlargement of the pseudoaneurysm, no episodes of hemoptysis, and no neurological complications during the 4-week follow-up period. Conclusion: Herein, we compare our case with other cancer-related pseudoaneurysms in the medical literature and summarize the clinical features and treatment of this unusual case. PMID:27495079

  1. Viscous Energy Loss in the Presence of Abnormal Aortic Flow

    PubMed Central

    Barker, A.J.; van Ooij, P.; Bandi, K.; Garcia, J.; Albaghdadi, M.; McCarthy, P.; Bonow, R. O.; Carr, J.; Collins, J.; Malaisrie, C.; Markl, M.

    2014-01-01

    Purpose To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses, and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Methods 4D flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n=12, age=37±10), patients with aortic dilation (n=16, age=52±8), and patients with aortic valve stenosis matched for age and aortic size (n=14, age=46±15), using a relationship between the 3D velocity field and viscous energy dissipation. Results Viscous energy loss was significantly elevated in the thoracic aorta for patients with dilated aorta (3.6±1.3 mW, p=0.024) and patients with aortic stenosis (14.3±8.2 mW, p<0.001) compared to healthy volunteers (2.3±0.9 mW). The same pattern of significant differences were seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2±1.1 mW, p=0.021) and patients with aortic stenosis (10.9±6.8 mW, p<0.001) were elevated compared to healthy volunteers (1.2±0.6 mW). Conclusion This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow. PMID:24122967

  2. Management of Aortic Aneurysms: Is Surgery of Historic Interest Only?

    PubMed

    Bacharach, J Michael; Wood, Emily A; Slovut, David P

    2015-11-01

    Since its advent in 1991, endovascular aortic aneurysm repair (EVAR) has become a mainstay of treatment for abdominal aortic aneurysms (AAA). Studies such as the comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR 1) trial, have demonstrated the effectiveness of EVAR in reducing perioperative mortality. Technological improvements in graft design and delivery account for an increasing utilization of endovascular repair. Newer branch and fenestrated graft designs have allowed for treatment of patients with complex aortic anatomy that previously could not be treated with EVAR. Endovascular repair, while dominant, is unlikely to eliminate the need for open repair or to relegate open surgery for AAA to historical interest only. The unprecedented adoption of EVAR has led to complications and modes of failure that were not seen with open repair. The rate of failure is markedly increased when endografts are used outside of the instructions for use (IFU). The long-term durability of fenestrated and investigational branch devices remains to be established. The demand for an endovascular approach by patients and the willingness of physicians to place endografts outside the anatomic IFU criteria may have resulted in the pendulum swinging too far away from open surgical management. The consequence of reduced open aortic surgeries is a concern for both patient care as well as training for vascular surgery fellows. Vascular surgery training programs will require innovative changes in training to assure that vascular surgery trainees will have the requisite skill and experience required to competently perform open surgical repair on what will undoubtedly be some of the most complex aortic pathology. PMID:26395644

  3. 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.

  4. Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis[S

    PubMed Central

    Vaisman, Boris L.; Demosky, Stephen J.; Stonik, John A.; Ghias, Mona; Knapper, Cathy L.; Sampson, Maureen L.; Dai, Cuilian; Levine, Stewart J.; Remaley, Alan T.

    2012-01-01

    The role of endothelial ABCA1 expression in reverse cholesterol transport (RCT) was examined in transgenic mice, using the endothelial-specific Tie2 promoter. Human ABCA1 (hABCA1) was significantly expressed in endothelial cells (EC) of most tissues except the liver. Increased expression of ABCA1 was not observed in resident peritoneal macrophages. ApoA-I-mediated cholesterol efflux from aortic EC was 2.6-fold higher (P < 0.0001) for cells from transgenic versus control mice. On normal chow diet, Tie2 hABCA1 transgenic mice had a 25% (P < 0.0001) increase in HDL-cholesterol (HDL-C) and more than a 2-fold increase of eNOS mRNA in the aorta (P < 0.04). After 6 months on a high-fat, high-cholesterol (HFHC) diet, transgenic mice compared with controls had a 40% increase in plasma HDL-C (P < 0.003) and close to 40% decrease in aortic lesions (P < 0.02). Aortas from HFHC-fed transgenic mice also showed gene expression changes consistent with decreased inflammation and apoptosis. Beneficial effects of the ABCA1 transgene on HDL-C levels or on atherosclerosis were absent when the transgene was transferred onto ApoE or Abca1 knockout mice. In summary, expression of hABCA1 in EC appears to play a role in decreasing diet-induced atherosclerosis in mice and is associated with increased plasma HDL-C levels and beneficial gene expression changes in EC. PMID:22039582

  5. Aortic Atherosclerosis in Systemic Lupus Erythematosus

    PubMed Central

    Roldan, Paola C; Ratliff, Michelle; Snider, Richard; Macias, Leonardo; Rodriguez, Rodrigo; Sibbitt, Wilmer; Roldan, Carlos A.

    2014-01-01

    Aortic atherosclerosis (AoA) defined as intima-media thickening or plaques and aortic stiffness (AoS) also considered an atherosclerotic process and defined as decreased vessel distensibility (higher pulse pressure to achieve similar degree of vessel distension) are common in patients with SLE. Immune-mediated inflammation, thrombogenesis, traditional atherogenic factors, and therapy-related metabolic abnormalities are the main pathogenic factors of AoA and AoS. Pathology of AoA and AoS suggests an initial subclinical endothelialitis or vasculitis, which is exacerbated by thrombogenesis and atherogenic factors and ultimately resulting in AoA and AoS. Computed tomography (CT) for detection of arterial wall calcifications and arterial tonometry for detection of increased arterial pulse wave velocity are the most common diagnostic methods for detecting AoA and AoS, respectively. MRI may become a more applicable and accurate technique than CT. Although transesophageal echocardiography accurately detects earlier and advanced stages of AoA and AoS, it is semi-invasive and cannot be used as a screening method. Although imaging techniques demonstrate highly variable prevalence rates, on average about one third of adult SLE patients may have AoA or AoS. Age at SLE diagnosis; SLE duration; activity and damage; corticosteroid therapy; metabolic syndrome; chronic kidney disease; and mitral annular calcification are common independent predictors of AoA and AoS. Also, AoA and AoS are highly associated with carotid and coronary atherosclerosis. Earlier stages of AoA and AoS are usually subclinical. However, earlier stages of disease may be causally related or contribute to peripheral or cerebral embolism, pre-hypertension and hypertension, and increased left ventricular afterload resulting in left ventricular hypertrophy and diastolic dysfunction. Later stages of disease predisposes to visceral ischemia, aortic aneurysms and aortic dissection. Even earlier stages of AoA and Ao

  6. Transfemoral Valve-in-Valve Transcatheter Aortic Valve Implantation (TAVI) in a Patient With Previous Endovascular Aortic Repair (EVAR).

    PubMed

    Ruparelia, Neil; Panoulas, Vasileios F; Frame, Angela; Nathan, Anthony W; Ariff, Ben; Jaffer, Usman; Sutaria, Nilesh; Chukwuemeka, Andrew; Mikhail, Ghada W; Malik, Iqbal S

    2016-07-01

    A 90-year-old man presented with increasing exertional breathlessness. He had previous implantation of a Perimount bioprosthetic aortic valve (Edwards Lifesciences) and coronary artery bypass graft surgery. Due to severe transvalvular bioprosthetic regurgitation with preserved left ventricular dimensions and ejection fraction, the heart team decided on valve-in- valve transcatheter aortic valve implantation via the transfemoral route in view of the patient's prohibitively high surgical and anesthetic risk. The patient had an uncomplicated recovery and was symptomatically much improved at 3-month follow-up. PMID:27342209

  7. Abdominal aortic aneurysms: case report

    PubMed Central

    Hadida, Camille; Rajwani, Moez

    1998-01-01

    A 71-year-old male presented to a chiropractic clinic with subacute low back pain. While the pain appeared to be mechanical in nature, radiographic evaluation revealed an abdominal aortic aneurysm, which required the patient to have vascular surgery. This case report illustrates the importance of the history and physical examination in addition to a thorough knowledge of the features of abdominal aortic aneurysms. The application of spinal manipulative therapy in patients with (AAA) is also discussed. ImagesFigure 1Figure 2Figure 3

  8. Aortic and other arterial injuries.

    PubMed Central

    Hardy, J D; Raju, S; Neely, W A; Berry, D W

    1975-01-01

    Three hundred sixty arterial injuries in 353 patients are reviewed. They covered a wide spectrum of injuries and included 36 aortic injuries and 19 cases of carotid truama. The mortality rate of 12% was in large part due to aortic injuries. Shock was the predominant cause of death. Infection was the most frequent non-fatal complication. Pulmonary complications were surprisingly uncommon. With methods and techniques discussed in the paper, 90% satisfactory end results were achieved. The amputation rate was 6% where extremity injuries were involved. Images Fig. 11. Fig. 13. PMID:1130881

  9. [Quadricuspid Aortic Valve: Report of a Case].

    PubMed

    Ryugo, Masahiro; Takasaki, Taiichi

    2016-02-01

    A 69-year-old woman with general fatigue was admitted to our hospital for further examination of mediastinal lymph node swelling. Mediastinal lymph node sampling was planned. Preoperative transthoracic echocardiography revealed severe aortic regurgitation, and aortic valve replacement combined with mediastinal lymph node sampling was performed. Following lymph node sampling, the ascending aorta was opened, and the aortic valve was found to be quadricuspid. An accessory cusp was existed between the left coronary cusp and the non coronary cusp. Aortic valve replacement was successfully performed. A quadricuspid aortic valve is a very rare anomaly. PMID:27075156

  10. EXPERIMENTAL MODELLING OF AORTIC ANEURYSMS

    PubMed Central

    Doyle, Barry J; Corbett, Timothy J; Cloonan, Aidan J; O’Donnell, Michael R; Walsh, Michael T; Vorp, David A; McGloughlin, Timothy M

    2009-01-01

    A range of silicone rubbers were created based on existing commercially available materials. These silicones were designed to be visually different from one another and have distinct material properties, in particular, ultimate tensile strengths and tear strengths. In total, eleven silicone rubbers were manufactured, with the materials designed to have a range of increasing tensile strengths from approximately 2-4MPa, and increasing tear strengths from approximately 0.45-0.7N/mm. The variations in silicones were detected using a standard colour analysis technique. Calibration curves were then created relating colour intensity to individual material properties. All eleven materials were characterised and a 1st order Ogden strain energy function applied. Material coefficients were determined and examined for effectiveness. Six idealised abdominal aortic aneurysm models were also created using the two base materials of the study, with a further model created using a new mixing technique to create a rubber model with randomly assigned material properties. These models were then examined using videoextensometry and compared to numerical results. Colour analysis revealed a statistically significant linear relationship (p<0.0009) with both tensile strength and tear strength, allowing material strength to be determined using a non-destructive experimental technique. The effectiveness of this technique was assessed by comparing predicted material properties to experimentally measured methods, with good agreement in the results. Videoextensometry and numerical modelling revealed minor percentage differences, with all results achieving significance (p<0.0009). This study has successfully designed and developed a range of silicone rubbers that have unique colour intensities and material strengths. Strengths can be readily determined using a non-destructive analysis technique with proven effectiveness. These silicones may further aid towards an improved understanding of the

  11. A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays

    PubMed Central

    2012-01-01

    Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS −786 T > C, the allele frequencies were 0.87 (T allele

  12. [Aortic inflammatory lesions in Behçet's disease].

    PubMed

    Desbois, A-C; Wechsler, B; Cacoub, P; Saadoun, D

    2016-04-01

    The arterial lesions affect about 10% of patients with Behçet's disease (BD). Aortic inflammatory involvement includes predominantly aortic aneurysmal lesions affecting most often the abdominal aorta. They account for the severity of the disease and are a leading cause of death when they hit the aorta or pulmonary arteries. Within the arterial lesions of BD, aortic involvement is, with femoral lesions, the most common site involved (18-28% of patients with vascular disease). Unlike other large vessels vasculitis (i.e. giant cell arteritis and Takayasu's arteritis) diffuse aortitis is observed in less than 5% of patients with BD. Aortic lesions of BD may be asymptomatic (systematic imaging or occasionally associated with other vascular event) or be revealed by the occurrence of abdominal, thoracic or lumbar pain, or an aortic valve insufficiency. Fever is frequently associated. Increase in acute phase reactants is common in these patients. Histological analysis may show infiltration by lymphocytes, neutrophils and plasma cells in the media and adventitia and a proliferation of the vasa vasorum in the media as well as a fibroblastic proliferation. In the later phase, a fibrous thickening of the media and adventitia is observed as well as a proliferation and thickening of the vasa vasorum. The therapeutic management should always include a medical treatment for the control of inflammation (corticosteroids, immunosuppressive drugs and/or biotherapy) and often an endovascular or surgical treatment if the aneurysm is threatening. The choice between endovascular or surgical treatment is considered case by case, depending on the experience of the team, anatomical conditions and of the clinical presentation. In this review, we provide a detailed and updated review of the literature to describe the aortic inflammatory damage associated with Behçet's disease. PMID:26611428

  13. Management of hypoplastic aortic arch associated with neonatal coarctation.

    PubMed

    Caspi, J; Ilbawi, M N; Muster, A; Roberson, D; Arcilla, R

    1994-12-01

    Controversy still exists as to whether hypoplastic aortic arch frequently associated with neonatal coarctation, should be enlarged at the time of coarctation repair. To determine the indications for and the outcome of repair of hypoplastic aortic arch, pre- and postoperative angiograms/echocardigraphy of 77 cases with isolated (n = 25, Group 1) or complex (n = 52, Group 2) neonatal coarctation operated upon between 1/80 and 12/89 were reviewed. Age was 5-14 days (mean 8 +/- 1.6). Aortic arch/ascending aorta diameter ratio (AR/AA) as a measure of the degree of aortic arch hypoplasia was 0.39-0.64 (0.52 +/- 0.04) in isolated and 0.15-0.47 (0.34 +/- 0.06) in complex coarctation (p < 0.05). Left subclavian flap aortoplasty was used in 72 patients; alone in 25, in combination with pulmonary artery banding in 43 patients, and simultaneously with intracardiac repair in 4 patients. Extensive reconstruction of aortic arch and coarctation with synthetic patch was performed in the remaining 5 patients (AR/AO = 0.16 +/- 0.03) using cardiopulmonary by-pass at the time of intracardiac repair. Operative mortality was 2/76 (2.5%). Follow-up is 6.6 +/- 1.4 years. Recoarctation occurred in 3 patients (4%). AR/AA increased to 0.86 +/- 0.1 in isolated (p < 0.05 vs preoperative) and to 0.7 +/- 0.1 in complex coarctation (p < 0.05 vs preoperative). In the majority of cases, hypoplastic aortic arch associated with coarctation grows satisfactorily following simple repair of coarctation with no significant residual narrowing.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Medical management of small abdominal aortic aneurysms.

    PubMed

    Baxter, B Timothy; Terrin, Michael C; Dalman, Ronald L

    2008-04-01

    Abdominal aortic aneurysm is a common condition that may be lethal when it is unrecognized. Current guidelines suggest repair as the aneurysm diameter reaches 5.0 to 5.5 cm. Most aortic aneurysms are detected incidentally when imaging is done for other purposes or through screening programs. Ninety percent of these aneurysms are below the threshold for intervention at the time of detection. A number of studies have sought to determine factors that lead to progression of aneurysmal disease that might be amenable to intervention during this period of observation. We review these studies and make recommendations for the medical management of small abdominal aortic aneurysms. On the basis of our current knowledge of the causes of aneurysm, a number of approaches have been proposed to prevent progression of aneurysmal disease. These include hemodynamic management, inhibition of inflammation, and protease inhibition. The American College of Cardiology/American Heart Association clinical practice guidelines rules of evidence have helped to define strength of evidence to support these approaches. Level A evidence (from large randomized trials) is available to indicate that observation of small aneurysms in men is safe up to a size of 5.5 cm and that propranolol does not inhibit aneurysm expansion. Level B evidence (from small randomized trials) suggests that roxithromycin or doxycycline will decrease the rate of aneurysm expansion. A number of studies agree that tobacco use is associated with an increased rate of aneurysm expansion. Level B and C evidence is available to suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may inhibit aneurysm expansion. There are animal data but no human data demonstrating that angiotensin-converting enzyme inhibitors or losartan, an angiotensin receptor blocker, will decrease the rate of AAA expansion. A pharmacological agent without important side effects that inhibited aneurysm expansion could change

  15. [Effects of atrial natriuretic peptide on aortic baroreceptor activity in rats].

    PubMed

    Ma, X Y; Zhang, W Y; Ho, S Y

    1994-10-01

    Effects of atriopeptin III (AP III) on the aortic baroreceptor activity in rats were studied in the isolated aorta arch-aortic nerve preparation in situ. By perfusing the isolated aortic arch with AP III (2.0 micrograms/ml) in rats, at constant intra-aortic pressure (IAP) of 13.3 kPa, the integral of aortic nerve activity (IANA) was increased by 64 +/- 27% (P < 0.001), the stepwise increases and decreases of IAP were correspondingly accompanied by increase and decrease in IANA, while the saturation pressure (SP) and the operating range (OR) of aortic baroreceptor activity were decreased from 22.5 +/- 0.5 to 21.3 +/- 0.5 kPa (P < 0.05) and 12.1 +/- 0.4 to 10.6 +/- 0.4 (P < 0.05), respectively, and the threshold pressure (TP) did not show any changes. The function curve of aortic baroreceptor was shifted to left and upward, and the peak integral value (PIV) and the peak slope (PS) of the curve were increased from 508 +/- 66 to 730 +/- 52% (P < 0.05), 55.6 +/- 7.5 to 93.2 +/- 6.8%.kPa-1 (P < 0.05), respectively. After washing out of AP III, the IANA returned to the control level. By perfusing the aortic arch with sodium nitroprusside (NP, 1.0 microgram/ml), at constant intra-aortic pressure (IAP) of 13.3 kPa, although the IANA was decreased as compared with the control, there was no statistical significance (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Vascular airway compression management in a case of aortic arch and descending thoracic aortic aneurysm

    PubMed Central

    Kumar, Alok; Dutta, Vikas; Negi, Sunder; Puri, G. D.

    2016-01-01

    Airway compression due to distal aortic arch and descending aortic aneurysm repair has been documented. This case of tracheal and left main stem bronchus compression due to aortic aneurysm occurred in a 42-year-old man. The airway compression poses a challenge for the anesthesiologist in airway management during aortic aneurysm repair surgery. The fiber-optic bronchoscope is very helpful in decision-making both preoperatively and postoperatively in such cases. We report a case of airway compression in a 42-year-old patient who underwent elective distal aortic arch and descending aortic aneurysm repair. PMID:27397474

  17. Traumatic aortic regurgitation combined with descending aortic pseudoaneurysm secondary to blunt chest trauma.

    PubMed

    Kim, Siho; Park, Joon Suk; Yoo, Seung Min; Kim, Kyung Ho; Yang, Woo-In; Sung, Jung-Hoon; Kim, In Jai; Lim, Sang-Wook; Cha, Dong-Hun; Moon, Jae-Youn

    2014-09-23

    Rupture of the aorta is a relatively rare complication of blunt chest trauma, and traumatic rupture of the aortic valve is even rarer. Even though both result from blunt chest trauma, the causative mechanisms of aortic valve injury differ from those of descending aortic rupture. There are no previous reports in the literature of simultaneous injuries to both the descending aorta and the aortic valve. We report a case of a 70-year-old man who presented with traumatic aortic regurgitation combined with traumatic pseudoaneurysm of the aortic isthmus following blunt chest trauma, and its successful repair with a hybrid surgical strategy.

  18. Chronic Type A Aortic Dissection

    PubMed Central

    Hynes, Conor F.; Greenberg, Michael D.; Sarin, Shawn; Trachiotis, Gregory D.

    2016-01-01

    Stanford Type A aortic dissection is a rapidly progressing disease process that is often fatal without emergent surgical repair. A small proportion of Type A dissections go undiagnosed in the acute phase and are found upon delayed presentation of symptoms or incidentally. These chronic lesions may have a distinct natural history that may have a better prognosis and could potentially be managed differently then those presenting acutely. The method of repair depends on location and extent of the false lumen, as well as involvement of critical structures and branch arteries. Surgical repair techniques similar to those employed for acute dissection management are currently first-line therapy for chronic cases that involve the aortic valve, sinuses of Valsalva, coronary arteries, and supra-aortic branch arteries. In patients with high-risk for surgery, endovascular repairs have been successful, and active development of delivery systems and grafts will continue to enhance outcomes. We present two cases of chronic Type A aortic dissection and review the current literature.

  19. Aortic injuries in newer vehicles.

    PubMed

    Ryb, Gabriel E; Dischinger, Patricia C; Kleinberger, Michael; McGwin, Gerald; Griffin, Russell L

    2013-10-01

    The occurrence of AI was studied in relation to vehicle model year (MY) among front seat vehicular occupants, age≥16 in vehicles MY≥1994, entered in the National Automotive Sampling System Crashworthiness Data System between 1997 and 2010 to determine whether newer vehicles, due to their crashworthiness improvements, are linked to a lower risk of aortic injuries (AI). MY was categorized as 1994-1997, 1998-2004, or 2005-2010 reflecting the introduction of newer occupant protection technology. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals for the association between AI and MY independent of possible confounders. Analysis was repeated, stratified by frontal and near lateral impacts. AI occurred in 19,187 (0.06%) of the 31,221,007 (weighted) cases, and contributed to 11% of all deaths. AIs were associated with advanced age, male gender, high BMI, near-side impact, rollover, ejection, collision against a fixed object, high ΔV, vehicle mismatch, unrestrained status, and forward track position. Among frontal crashes, MY 98-04 and MY 05-10 showed increased adjusted odds of AI when compared to MY 94-97 [OR 1.84 (1.02-3.32) and 1.99 (0.93-4.26), respectively]. In contrast, among near-side impact crashes, MY 98-04 and MY 05-10 showed decreased adjusted odds of AI [OR 0.50 (0.25-0.99) and 0.27 (0.06-1.31), respectively]. While occupants of newer vehicles experience lower odds of AI in near side impact crashes, a higher AI risk is present in frontal crashes. PMID:23831451

  20. Pleural Empyema and Aortic Aneurysm

    PubMed Central

    Wu, Ching-Yang; Su, Ta-Wei; Huang, Kuo-Yang; Ko, Po-Jen; Yu, Sheng-Yueh; Kao, Tsung-Chi; Shen, Te-Chun; Chou, Tzu-Yi; Lin, Cheng-Li; Kao, Chia-Hung

    2015-01-01

    Abstract Pleural empyema (PE) may evolve into necrosis, fistula in the thorax, and sepsis; thus, it is also associated with high mortality. We investigated and analyzed the risk of aortic aneurysm (AA) in a cohort study of patients with PE. A total of 34,250 patients diagnosed with PE were identified as the PE cohort, and 137,000 patients without PE were selected randomly as the control group and matched by sex, age, and index year of PE diagnosis. Patients ages 20 years and younger with a history of AA were excluded. The risk of AA was analyzed using a Cox proportional hazards regression model. Excess risk of AA development was 1.69-fold higher in PE patients (adjusted hazard ratio [aHR] = 1.69; 95% confidence interval [CI] = 1.39–2.05) compared with non-PE patients. The patients with PE exhibited a greater adjusted risk of AA (aHR = 2.01; CI = 1.44–2.81) even if they did not have any of the 9 comorbidities included in our analysis (diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, heart failure, cardiac artery disease, stroke, bacterial endocarditis, and rheumatic endocarditis). Compared with the patients without any of the 9 comorbidities or PE, the patients with only PE had a greater risk of developing AA (aHR = 2.00; CI = 1.43–2.79). The PE cohort had a significantly higher cumulative incidence of AA than the non-PE cohort did during 12 years of follow-up. In a large-scale cohort, patients with PE are linked with an increased risk of AA. PMID:26632741

  1. Stentless aortic valve replacement: an update

    PubMed Central

    Kobayashi, Junjiro

    2011-01-01

    Although porcine aortic valves or pericardial tissue mounted on a stent have made implantation techniques easier, these valves sacrifice orifice area and increase stress at the attachment of the stent, which causes primary tissue failure. Optimizing hemodynamics to prevent patient–prosthetic mismatch and improve durability, stentless bioprostheses use was revived in the early 1990s. The purpose of this review is to provide a current overview of stentless valves in the aortic position. Retrospective and prospective randomized controlled studies showed similar operative mortality and morbidity in stented and stentless aortic valve replacement (AVR), though stentless AVR required longer cross-clamp and cardiopulmonary bypass time. Several cohort studies showed improved survival after stentless AVR, probably due to better hemodynamic performance and earlier left ventricular (LV) mass regression compared with stented AVR. However, there was a bias of operation age and nonrandomization. A randomized trial supported an improved 8-year survival of patients with the Freestyle or Toronto valves compared with Carpentier–Edwards porcine valves. On the contrary, another randomized study did not show improved clinical outcomes up to 12 years. Freedom from reoperation at 12 years in Toronto stentless porcine valves ranged from 69% to 75%, which is much lower than for Carpentier–Edwards Perimount valves. Cusp tear with consequent aortic regurgitation was the most common cause of structural valve deterioration. Cryolife O’Brien valves also have shorter durability compared with stent valves. Actuarial freedom from reoperation was 44% at 10 years. Early prosthetic valve failure was also reported in patients who underwent root replacement with Shelhigh stentless composite grafts. There was no level I or IIa evidence of more effective orifice area, mean pressure gradient, LV mass regression, surgical risk, durability, and late outcomes in stentless bioprostheses. There is no

  2. 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

  3. Assessment of Aortic Elasticity in Patients with Celiac Disease

    PubMed Central

    Çekin, Ayhan Hilmi; Arslan, Şakir; Çağırcı, Göksel; Küçükseymen, Selçuk; Çay, Serkan; Harmandar, Ferda Akbay; Yeşil, Bayram

    2016-01-01

    Background and Objectives Celiac disease (CD) is a chronic autoimmune disorder induced by dietary gluten intake by individuals who are genetically sensitive. Many studies report an increased risk of cardiovascular diseases in such patients. The aim of this study is to assess aortic elasticity properties in patients with CD that may be associated with an increased risk of cardiovascular disease. Subjects and Methods Eighty-one patients diagnosed with CD by antibody test and biopsy and 63 healthy volunteers were included in this prospective study. Electrocardiographic and echocardiographic examinations were performed. Results The CD group did not have any differences in the conventional echocardiographic parameters compared to the healthy individuals. However, patients in the CD group had an increased aortic stiffness beta index (4.3±2.3 vs. 3.6±1.6, p=0.010), increased pressure strain elastic modulus (33.6±17.0 kPa vs. 28.5±16.7 kPa, p=0.037), decreased aortic distensibility (7.0±3.0×10-6 cm2/dyn vs. 8.2±3.6×10-6 cm2/dyn, p=0.037), and similar aortic strain (17.9±7.7 vs. 16.0±5.5, p=0.070) compared to the control group. Patients with CD were found to have an elevated neutrophil/lymphocyte ratio compared to the control group (2.54±0.63 vs. 2.24±0.63, p=0.012). However, gluten-free diet and neutrophil/lymphocyte ratio were not found to be associated with aortic elasticity. Conclusion Patients with CD had increased aortic stiffness and decreased aortic distensibility. Gluten-free diet enabled the patients with CD to have a reduction in the inflammatory parameters whereas the absence of a significant difference in the elastic properties of the aorta may suggest that the risk of cardiovascular disease persists in this patient group despite a gluten-free diet. PMID:27014355

  4. Decellularized aortic homografts for aortic valve and aorta ascendens replacement†

    PubMed Central

    Tudorache, Igor; Horke, Alexander; Cebotari, Serghei; Sarikouch, Samir; Boethig, Dietmar; Breymann, Thomas; Beerbaum, Philipp; Bertram, Harald; Westhoff-Bleck, Mechthild; Theodoridis, Karolina; Bobylev, Dmitry; Cheptanaru, Eduard; Ciubotaru, Anatol; Haverich, Axel

    2016-01-01

    OBJECTIVES The choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults. METHODS This prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 ± 14.6 years (range 0.2–65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH. RESULTS Thirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 ± 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 ± 3.7 mm (range, 10–29 mm), the average peak gradient was 14 ± 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 ± 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 ± 0.7 cm2. DAH annulus z-values were 1.1 ± 1.1 at implantation and 0.7 ± 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 ± 7% and 78 ± 16 ml/m2 body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 ± 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation

  5. Inter-individual variance and cardiac cycle dependency of aortic root dimensions and shape as assessed by ECG-gated multi-slice computed tomography in patients with severe aortic stenosis prior to transcatheter aortic valve implantation: is it crucial for correct sizing?

    PubMed

    Lehmkuhl, Lukas; Foldyna, Borek; Von Aspern, Konstantin; Lücke, Christian; Grothoff, Matthias; Nitzsche, Stefan; Kempfert, Jörg; Haensig, Martin; Rastan, Ardawan; Walther, Thomas; Mohr, Friedrich-Wilhelm; Gutberlet, Matthias

    2013-03-01

    To evaluate the inter-individual variance and the variability of the aortic root dimensions during the cardiac cycle by computed tomography (CT) in patients with severe aortic stenosis prior to transcatheter aortic valve implantation (TAVI). Fifty-six patients (m/w = 16/40, 81 ± 6.8 years), scheduled for a transapical aortic valve implantation with available preprocedural ECG-gated CT were retrospectively included. The evaluation included sizing of the aortic annulus and the aortic sinus, measurements of the coronary topography, aortic valve planimetry and scoring of calcification. The new defined aortic annulus sphericity ratio revealed a mostly elliptical shape with increasing diastolic deformation. The calculated effective diameter (ED), determined from the annulus' lumen area, turned out to be the parameter least affected from cardiac cycle changes while systolic and diastolic annulus dimensions and shape (diameter and area) differed significantly (p < 0.001). In about 70 % of the patients with relevant paravalvular leaks the finally implanted prosthesis was too small according to the CT based calculated ED. The ostial height of the coronaries showed a high variability with a critical minimum range <5 mm. The degree of the aortic calcification did not have an influence on the aortic annulus deformation during the cardiac cycle, but on the occurrence of paravalvular leaks. The aortic root anatomy demonstrated a high inter-individual variability and cardiac cycle dependency. These results must be strongly considered during the patient evaluation prior to TAVI to avoid complications. The systolic effective diameter, as measured by ECG-gated CT, represents an appropriate parameter for sizing the aortic annulus.

  6. Stent-Grafts for Unruptured Abdominal Aortic Aneurysms: Current Status

    SciTech Connect

    Rose, John

    2006-06-15

    Aortic stent-grafts were introduced at the beginning of the 1990s as a less invasive method of dealing with aortic aneurysms in patients with poor cardiovascular reserve. The numbers of procedures performed worldwide has increased exponentially despite the current lack of any substantial evidence for long-term efficacy in comparison with the gold standard of open surgical grafting. This review summarizes the evolution of the abdominal aortic stent-graft, the techniques used for assessment and deployment, and the effect of the procedure on both the patient and the device. The recent publication of two national multicenter trials has confirmed that the endovascular technique confers a 2.5-fold reduction in 30-day mortality in comparison with open surgery. However, over 4 years of follow-up, there is a 3-fold increase in the risk of reintervention and the overall costs are 30% greater with endovascular repair. Although the improvement in aneurysm-related mortality persists in the mid-term, because of the initial reduction in perioperative mortality, the all-cause mortality rate at 4 years is actually no better than for open surgery. Longer-term data from the randomized trials are awaited as well as results from the latest trials utilizing state-of-the-art devices. Whilst the overall management of abdominal aortic aneurysms has undoubtedly benefited from the introduction of stent-grafts, open repair currently remains the gold standard treatment.

  7. Vascular Endothelial Growth Factor Increases Endothelial Nitric Oxide Synthase Transcription In Huvec Cells

    PubMed Central

    Koai, Esther; Rios, Tibisay Rincon; Edwards, John

    2016-01-01

    Although it is known that VEGF increases eNOS protein, the mechanisms responsible remain unclear. To determine if VEGF alters eNOS transcription, human umbilical vein endothelial cells were transfected with reporters under the control of the eNOS promoter and stimulated with VEGF165. VEGF significantly increased eNOS-mRNA after 2 hours exposure. VEGF significantly increased eNOS reporter activity as early as one hour (268±32%), but this increase returned to baseline after 6 hours. Using deletion constructs, the VEGF response region was initially localized to within the −722/−494 region. GMSA indicated that VEGF increased DNA binding to both a cAMP-like and AP1-like response elements. Site-specific mutations and heterologous constructs indicated that the site centered at AP1-like site was both necessary and sufficient to meditate VEGF transcriptional activation. These results indicate that VEGF rapidly activates eNOS transcription prior to a rise eNOS-mRNA, an effect mediated by a cis-trans interaction localized to an AP1-like site within the eNOS promoter.

  8. TGFB2 loss of function mutations cause familial thoracic aortic aneurysms and acute aortic dissections associated with mild systemic features of the Marfan syndrome

    PubMed Central

    Boileau, Catherine; Guo, Dong-Chuan; Hanna, Nadine; Regalado, Ellen S.; Detaint, Delphine; Gong, Limin; Varret, Mathilde; Prakash, Siddharth; Li, Alexander H.; d’Indy, Hyacintha; Braverman, Alan C.; Grandchamp, Bernard; Kwartler, Callie S.; Gouya, Laurent; Santos-Cortez, Regie Lyn P.; Abifadel, Marianne; Leal, Suzanne M.; Muti, Christine; Shendure, Jay; Gross, Marie-Sylvie; Rieder, Mark J.; Vahanian, Alec; Nickerson, Deborah A.; Michel, Jean Baptiste; Jondeau, Guillaume; Milewicz, Dianna M.

    2014-01-01

    A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner. Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease, followed by whole exome sequencing of affected relatives, identified causative mutations in TGFB2. These mutations, a frameshift mutation in exon 6 and a nonsense mutation in exon 4, segregated with disease with a combined LOD score of 7.7. Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified two additional TGFB2 mutations. TGFB2 encodes the transforming growth factor beta-2 (TGF-β2) and the mutations are predicted to cause haploinsufficiency for TGFB2, but aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining. Thus, haploinsufficiency of TGFB2 predisposes to thoracic aortic disease, suggesting the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta. PMID:22772371

  9. "How I do it: utilization of high-pressure sealants in aortic reconstruction"

    PubMed Central

    Elefteriades, John A

    2009-01-01

    Background Suture-line hemostasis, reinforcement of friable tissue, and adhesion prevention are key concerns for patients undergoing cardiac surgery for aortic reconstruction. Failure to secure hemostasis at anastomotic junctures and reinforce fragile tissue may lead to increased blood loss, additional blood product requirements, increased operative time, and, in extreme cases, reoperation. Patients with aortic pathology may also be at higher risk for reoperation, and adhesion formation from prior surgery is an added risk at resternotomy. The advent of high-pressure sealants has been of benefit in helping to alleviate these perioperative challenges. Methods The author utilizes two high-pressure sealants for aortic reconstructive procedures. The first is made of two polymers of polyethylene glycol (PEG) [Coseal®, Baxter Healthcare, Corporation], and is used to secure anastomotic suture-line hemostasis and for adhesion prevention. The second is a bovine serum albumin-glutaraldehyde (BSAG) glue [BioGlue®, CryroLife, Inc.], used for the repair of dissected aortic tissue and in reinforcing ("tanning") fragile aortic tissues. The techniques for application in select aortic reconstruction procedures are described. Results To substantiate the hemostatic clinical benefit observed by the author, 60 consecutive major thoracic aortic operations in 57 patients in whom PEG sealant was used were retrospectively reviewed. Although comparisons with other agents were not performed for this descriptive report, bleeding results were very favorable for these types of operations. The strong clinical impression is that topical hemostatic application of PEG sealant to anastomotic suture lines is helpful in preventing bleeding. Conclusion In major aortic reconstructive procedures the need for anastomotic sealing performance, reinforcement of friable tissues, and adhesion prevention should not be underrated. High-pressure surgical sealants represent an important surgical adjunct, and the

  10. Coronary Obstruction Following Transcatheter Aortic Valve Implantation

    PubMed Central

    Ribeiro, Henrique Barbosa; Sarmento-Leite, Rogério; Siqueira, Dimytri A. A.; Carvalho, Luiz Antônio; Mangione, José Armando; Rodés-Cabau, Josep; Perin, Marco A.; de Brito, Fábio Sandoli

    2014-01-01

    Background Transcatheter aortic valve implantation (TAVI) was established as an important alternative for high-risk patients with severe aortic stenosis. However, there are few data in the literature regarding coronary obstruction, that although rare, is a potentially fatal complication. Objective Evaluate this complication in Brazil. Methods We evaluated all patients presenting coronary obstruction from the Brazilian Registry of TAVI. Main baseline and procedural characteristics, management of the complication, and clinical outcomes were collected from all patients. Results From 418 consecutive TAVI procedures, coronary obstruction occurred in 3 cases (incidence of 0.72%). All patients were women, without prior coronary artery bypass grafting (CABG), and with mean age of 85 ± 3 years, logistic EuroSCORE of 15 ± 6% and STS-PROM score of 9 ± 4%. All of the cases were performed with balloon-expandable Sapien XT prosthesis. In one patient, with pre-procedural computed tomography data, coronary arteries presented a low height and a narrow sinus of Valsalva. All patients presented with clinically significant severe maintained hypotension, immediately after valve implantation, and even though coronary angioplasty with stent implantation was successfully performed in all cases, patients died during hospitalization, being two periprocedurally. Conclusion Coronary obstruction following TAVI is a rare but potentially fatal complication, being more frequent in women and with the balloon-expandable prosthesis. Anatomical factors might be related with its increased occurrence, highlighting the importance of a good pre-procedural evaluation of the patients in order to avoid this severe complication. PMID:24652089

  11. Subtle-discrete aortic dissection without bulging of the aortic wall. A rare but lethal lesion.

    PubMed

    Kalogerakos, Paris Dimitrios; Kampitakis, Emmanouil; Pavlopoulos, Dionisios; Chalkiadakis, George; Lazopoulos, George

    2016-08-01

    We report a subtle-discrete aortic dissection, without bulging of the aortic wall or aneurysm or valve pathology or periaortic effusion, which resulted in a lethal cardiac tamponade to a 35-year-old male. PMID:27357491

  12. Aromatase Is Required for Female Abdominal Aortic Aneurysm Protection

    PubMed Central

    Johnston, William F.; Salmon, Morgan; Su, Gang; Lu, Guanyi; Ailawadi, Gorav; Upchurch, Gilbert R.

    2014-01-01

    Objective The protective effects of female gender on the development of abdominal aortic aneurysms (AAAs) have been attributed to anti-inflammatory effects of estrogen. All estrogen synthesis is dependent upon the enzyme aromatase, which is located both centrally in the ovaries and peripherally in adipose tissue, bone, and vascular smooth muscle cells. It is hypothesized that deletion of aromatase in both ovaries and peripheral tissues would diminish the protective effect of female gender and would be associated with increased aortic diameter in female mice. Methods Male and female 8–10 week-old mice with aromatase (wild type: WT) and without aromatase (ArKO) underwent elastase aortic perfusion with aortic harvest 14 days following. To evaluate the contribution of central and peripheral estrogen conversion, female WT mice were compared to female WT and ArKO mice that had undergone ovariectomy (ovx) at 6 weeks followed by elastase perfusion at 8–10 weeks. At aortic harvest, maximal aortic dilation was measured and samples were collected for immunohistochemistry and protein analysis. Serum was collected for serum estradiol concentrations. Groups were compared with analysis of variance (ANOVA). Human and mouse AAA cross-sections were analyzed with confocal immunohistochemistry for aromatase, smooth muscle markers, and macrophage markers. Results Female WT mice had significant reduction in aortic dilation compared to male WT mice (F WT: 51.5±15.1% vs. M WT: 78.7±14.9%, p<0.005). The protective effects of female gender were completely eliminated with deletion of aromatase (F ArKO: 82.6±13.8%, p<0.05 vs. F WT). Ovariectomy increased aortic dilation in WT mice (F WT ovx: 70.6±11.7%, p<0.05 vs. F WT). Aromatase deletion with ovariectomy further increased aortic dilation compared to WT ovx mice (F ArKO ovx: 87.3±14.7%, p<0.001 vs. F WT and p<0.05 vs. F WT ovx). Accordingly, female ArKO ovx mice had significantly higher levels of proinflammatory cytokines MCP-1 and

  13. Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms

    PubMed Central

    Wågsäter, Dick; Vorkapic, Emina; van Stijn, Caroline M. W.; Kim, Jason; Lusis, Aldons J.; Eriksson, Per; Tangirala, Rajendra K.

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR−/−) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA. PMID:27659201

  14. Assessment of Altered 3D Blood Characteristics in Aortic Disease by Velocity Distribution Analysis

    PubMed Central

    Garcia, Julio; Barker, Alex J; van Ooij, Pim; Schnell, Susanne; Puthumana, Jyothy; Bonow, Robert O; Collins, Jeremy D; Carr, James C; Markl, Michael

    2014-01-01

    Purpose To test the feasibility of velocity distribution analysis for identifying altered 3D flow characteristics in patients with aortic disease based on 4D flow MRI volumetric analysis. Methods Forty patients with aortic (Ao) dilation (mid ascending aortic diameter MAA=40±7 mm, age=56±17 yr, 11 females) underwent cardiovascular MRI. Four groups were retrospectively defined: mild Ao dilation (n=10, MAA<35 mm); moderate Ao dilation (n=10, 3545 mm); Ao dilation+aortic stenosis AS (n=10, MAA>35 mm and peak velocity >2.5m/s). 3D PC-MR angiograms were computed and used to obtain a 3D segmentation of the aorta which was divided into four segments: root, ascending aorta, arch, descending aorta. Radial chart displays were used to visualize multiple parameters representing segmental changes in the 3D velocity distribution associated with aortic disease. Results Changes in the velocity field and geometry between cohorts resulted in distinct hemodynamic patterns for each aortic segment. Disease progression from mild to Ao dilation+AS resulted in significant differences (P<0.05) in flow parameters across cohorts and increased radial chart size for root and ascending aorta segments by 146% and 99%, respectively. Conclusion Volumetric 4D velocity distribution analysis has the potential to identify characteristic changes in regional blood flow patterns in patients with aortic disease. PMID:25252029

  15. Medical Treatment of Aortic Aneurysms in Marfan Syndrome and other Heritable Conditions

    PubMed Central

    Jost, Christine H. Attenhofer; Greutmann, Matthias; Connolly, Heidi M.; Weber, Roland; Rohrbach, Marianne; Oxenius, Angela; Kretschmar, Oliver; Luscher, Thomas F.; Matyas, Gabor

    2014-01-01

    Thoracic aortic aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS) and related aortic diseases as well as by inflammatory disorders such as giant cell arteritis or atherosclerosis. In all these conditions, cardiovascular risk factors, such as systemic arterial hypertension, may contribute to faster rate of aneurysm progression. Optimal medical management to prevent progressive aortic dilatation and aortic dissection is unknown. β-blockers have been the mainstay of medical treatment for many years despite limited evidence of beneficial effects. Recently, losartan, an angiotensin II type I receptor antagonist (ARB), has shown promising results in a mouse model of MFS and subsequently in humans with MFS and hence is increasingly used. Several ongoing trials comparing losartan to β-blockers and/or placebo will better define the role of ARBs in the near future. In addition, other medications, such as statins and tetracyclines have demonstrated potential benefit in experimental aortic aneurysm studies. Given the advances in our understanding of molecular mechanisms triggering aortic dilatation and dissection, individualized management tailored to the underlying genetic defect may be on the horizon of individualized medicine. We anticipate that ongoing research will address the question whether such genotype/pathogenesis-driven treatments can replace current phenotype/syndrome-driven strategies and whether other forms of aortopathies should be treated similarly. In this work, we review currently used and promising medical treatment options for patients with heritable aortic aneurysmal disorders. PMID:24527681

  16. Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome.

    PubMed

    Seckin, Yuksel; Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Cagin, Yasir Furkan; Gozukara, Harika; Bılgıc, Yılmaz; Yildirim, Oguzhan; Turkoz, Yusuf; Aksungur, Zeynep

    2016-01-01

    Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS. PMID:27594880

  17. Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome

    PubMed Central

    Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Bılgıc, Yılmaz; Yildirim, Oguzhan; Turkoz, Yusuf; Aksungur, Zeynep

    2016-01-01

    Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS.

  18. Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from diabetic eNOS knockout mice.

    PubMed

    Takahashi, Takamune; Harris, Raymond C

    2014-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study. PMID:25371905

  19. WLS-ENO: Weighted-least-squares based essentially non-oscillatory schemes for finite volume methods on unstructured meshes

    NASA Astrophysics Data System (ADS)

    Liu, Hongxu; Jiao, Xiangmin

    2016-06-01

    ENO (Essentially Non-Oscillatory) and WENO (Weighted Essentially Non-Oscillatory) schemes are widely used high-order schemes for solving partial differential equations (PDEs), especially hyperbolic conservation laws with piecewise smooth solutions. For structured meshes, these techniques can achieve high order accuracy for smooth functions while being non-oscillatory near discontinuities. For unstructured meshes, which are needed for complex geometries, similar schemes are required but they are much more challenging. We propose a new family of non-oscillatory schemes, called WLS-ENO, in the context of solving hyperbolic conservation laws using finite-volume methods over unstructured meshes. WLS-ENO is derived based on Taylor series expansion and solved using a weighted least squares formulation. Unlike other non-oscillatory schemes, the WLS-ENO does not require constructing sub-stencils, and hence it provides a more flexible framework and is less sensitive to mesh quality. We present rigorous analysis of the accuracy and stability of WLS-ENO, and present numerical results in 1-D, 2-D, and 3-D for a number of benchmark problems, and also report some comparisons against WENO.

  20. Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome

    PubMed Central

    Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Bılgıc, Yılmaz; Yildirim, Oguzhan; Turkoz, Yusuf; Aksungur, Zeynep

    2016-01-01

    Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS. PMID:27594880

  1. Spring retractor: a new adjunct for aortic valve surgery.

    PubMed

    Izzat, Mohammad Bashar

    2011-07-01

    We describe a new aortic retractor that is effective in maintaining aortic root geometry and providing for adequate intraoperative visual valve assessment, and therefore enables the surgeon to perform precise aortic valve repair or replacement procedures.

  2. Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis.

    PubMed

    Bunjevacki, Vera; Maksimovic, Nela; Jekic, Biljana; Milic, Vera; Lukovic, Ljiljana; Novakovic, Ivana; Damjanov, Nemanja; Radunovic, Goran; Damnjanovic, Tatjana

    2016-04-01

    Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction-restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course. PMID:26612436

  3. An Investigation of the Relationship between the eNOS Gene Polymorphism and Diagnosed Migraine.

    PubMed

    Güler, S; Gürkan, H; Tozkir, H; Turan, N; Çelik, Y

    2014-12-01

    We investigated the phenotype-genotype association of the following endothelial nitric oxide synthase (eNOS) gene polymorphisms, rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851, in patients suffering from migraine living in Edirne, Turkey. A total of 175 individuals, who had been diagnosed with migraine between April 2013 and December 2013, at the Neurology Department, Trakya University Medical Faculty, Edirne, Turkey, and 125 healthy controls were recruited. The above gene polymorphisms were analyzed from genomic DNA in both patient and control groups, using the pyro-sequencing method. The eNOS rs1799983 TT genotype frequency in migraine patients who had a headache duration of longer than 24 hours was statistically significantly higher than in patients who had migraine attacks that lasted under 24 hours (p = 0.047). In terms of the AGGTGGA haplotype, the severity of headache was statistically significant, and was found to be severe in 61.0% (p = 0.0001). Also in terms of the AGGTGGA haplotype, the duration of headache was statistically significant, and was >24 hours in 56.0% of patients (p = 0.008). In our study, there was no significant genotypephenotype relationship between eNOS rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851 gene polymorphisms and migraine patients with and without aura living in Edirne, Turkey. The AGGTGGA haplotype constitutes a risk in terms of the severity and the duration of headaches in patients with migraine. This risk is significantly higher in patients with migraine with aura than patients with migraine without aura.

  4. Type B Aortic Dissection Repair Using a Thoraflex Hybrid Prosthesis in a Complex Aortic Arch Anatomy

    PubMed Central

    Ghanem, Moussa Abi; Gomez-Sanchez, Mario; Chaufour, Xavier; Marcheix, Bertrand

    2016-01-01

    Thoracic endovascular aortic repair (TEVAR) is recognized as an attractive option to treat complicated Type B aortic dissection. Nevertheless, TEVAR is not always technically possible. We report the case of a 53-year-old male with complicated Type B aortic dissection, in the setting of a complex anomalous aortic arch anatomy with an aneurysmal aberrant right subclavian artery. He was successfully treated by the frozen elephant trunk technique using the Thoraflex hybrid graft.

  5. Severe Aortic Stenosis Associated with Unicommissural Unicuspid Aortic Valve in a Middle Aged Male

    PubMed Central

    Kwon, Hee-Jin; Kim, Song Soo; Sun, Byung Joo; Jin, Sun Ah; Kim, Jun-Hyung; Lee, Jae-Hwan; Choi, Siwan; Jeong, Jin-Ok; Seong, In-Whan

    2016-01-01

    Unicuspid aortic valve (UAV) is an extremely rare form of congenital aortic valvular abnormality. Although UAV shows similar clinical characteristics to bicuspid aortic valve, the clinical symptoms develop at earlier age and progress at a faster pace in UAV. In this report, we are presenting a 42-year-old male with severe aortic stenosis associated with unicommissural UAV. The patients underwent a successful Bentall operation. PMID:27721957

  6. Biaxial Creep Resistance and Structural Remodeling of the Aortic and Mitral Valves in Pregnancy.

    PubMed

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-08-01

    Pregnancy produces rapid, dramatic volume-overload changes to the maternal circulation. This paper examines pregnancy-induced structural-mechanical changes in bovine aortic and mitral heart valve leaflets. Valve leaflets were harvested from non-pregnant heifers and pregnant cows. Dimensions, biaxial extensibility and creep resistance were assessed and related to changes in the collagen network: histological leaflet and anatomic layer thicknesses plus collagen crimp, and biochemical collagen content. Collagen stability and crosslinking were assessed thermomechanically. Pregnancy altered both aortic and mitral valve leaflets. Both valves demonstrated biphasic changes in leaflet stretch, decreasing in early pregnancy and recovering by late pregnancy. Creep in leaflets from both valves was minimal and decreased even further with pregnancy in the mitral valve. There were valve-specific changes in preconditioning areal extension with pregnancy: increasing in the aortic valve and decreasing in the mitral valve. Leaflet area increased dramatically (84% aortic, 56% mitral), with thickening mainly in the fibrosa, accompanied by increases in collagen content (8% aortic, 16% mitral): together suggesting synthesis of new collagen. Collagen crimp was almost completely lost in pregnancy, with the denaturation temperature decreased by approximately 2 °C. Mature and total crosslinking increased, curiously without a significant increase in immature crosslinking. Mature aortic and mitral heart valve leaflets in the maternal cardiovascular system remodel substantially and similarly-despite their different embryological origins.

  7. 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.

  8. Ultrasound Screening for Abdominal Aortic Aneurysm

    PubMed Central

    2006-01-01

    Executive Summary Objective The aim of this review was to assess the effectiveness of ultrasound screening for asymptomatic abdominal aortic aneurysm (AAA). Clinical Need Abdominal aortic aneurysm is a localized abnormal dilatation of the aorta greater than 3 cm. In community surveys, the prevalence of AAA is reported to be between 2% and 5.4%. Abdominal aortic aneurysms are found in 4% to 8% of older men and in 0.5% to 1.5% of women aged 65 years and older. Abdominal aortic aneurysms are largely asymptomatic. If left untreated, the continuing extension and thinning of the vessel wall may eventually result in rupture of the AAA. Often rupture may occur without warning, causing acute pain. Rupture is always life threatening and requires emergency surgical repair of the ruptured aorta. The risk of death from ruptured AAA is 80% to 90%. Over one-half of all deaths attributed to a ruptured aneurysm take place before the patient reaches hospital. In comparison, the rate of death in people undergoing elective surgery is 5% to 7%; however, symptoms of AAA rarely occur before rupture. Given that ultrasound can reliably visualize the aorta in 99% of the population, and its sensitivity and specificity for diagnosing AAA approaches 100%, screening for aneurysms is worth considering as it may reduce the incidence of ruptured aneurysms and hence reduce unnecessary deaths caused by AAA-attributable mortality. Review Strategy The Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases to determine the effectiveness of ultrasound screening for abdominal aortic aneurysms. Case reports, letters, editorials, nonsystematic reviews, non-human studies, and comments were excluded. Questions asked: Is population-based AAA screening effective in improving health outcomes in asymptomatic populations? Is AAA screening acceptable to the population? Does this affect the

  9. Ascending aortic blood flow dynamics following intense exercise.

    PubMed

    Kilgour, R D; Sellers, W R

    1990-10-01

    The purpose of this study was to compare and contrast aortic blood flow kinetics during recovery from intense aerobic (maximal oxygen uptake test) and anaerobic (Wingate anaerobic power test) exercise. Fifteen healthy male subjects (VO2max = 56.1 +/- 5.8 mk/kg/min) participated in this study. Beat-to-beat peak aortic blood flow velocity (pkV) and acceleration (pkA) measurements were obtained by placing a 3.0 MHz continuous-wave ultrasonic transducer on the suprasternal notch at rest and during recovery (immediately post-exercise, 2.5 min, and 5.0 min) following the two exercise conditions. Peak velocity and acceleration significantly increased (p less than 0.01) from rest to immediately post-exercise and remained elevated throughout the 5-min recovery period. No differences were observed between the aerobic and anaerobic tests. Stroke distance significantly declined (p less than 0.01) immediately following exercise and progressively rose during the 5-min recovery period. The results indicate that: 1) aortic blood flow kinetics remained elevated during short-term recovery, and 2) intense aerobic and anaerobic exercise exhibit similar post-exercise aortic blood flow kinetics. PMID:2262232

  10. Magnesium and diltiazem relaxes phenylephrine-precontracted rat aortic rings

    PubMed Central

    Dogan, Mustafa; Peker, Recep O.; Donmez, Soner; Gokalp, Osman

    2012-01-01

    Perioperative vasospasm during cardiovascular surgery is a challenging problem. Several vasodilator agents are frequently utilized for its prevention in surgical practice. Magnesium and diltiazem both have known potential vasorelaxant effects. We planned to compare the efficacy of diltiazem and magnesium in relieving phenylephrine-precontracted rat aortic rings. Ten young adult female Wistar albino rats weighing 230–260 g were used in this study. The aortic rings in the organ bath equilibrated and reached their baseline tension. Precontraction was induced by 0.001 mmol/l phenylephrine and cumulative concentration–relaxation curves were obtained by consecutively increasing the addition of either diltiazem (10−6-0.1 mmol/l) or magnesium (0.1–10 mmol/l). The mean maximal relaxation responses observed by diltiazem and magnesium on separate aortic rings were 90 ± 3 and 53 ± 2%, respectively. The calculated EC50 of diltiazem was 0.01035 mmol/l, whereas the EC50 of magnesium was 4.064 mmol/l (P < 0.05). Both magnesium and diltiazem produced vasorelaxation on phenylephrine-precontracted rat aortic rings in this study, but the potency of diltiazem regarding the EC50 value was significantly higher than that of magnesium. Magnesium could be a candidate together with diltiazem to inhibit vasospasm on arterial grafts during coronary bypass surgery. PMID:22523136

  11. Vascular diseases: aortitis, aortic aneurysms, and vascular calcification.

    PubMed

    Ladich, Elena; Yahagi, Kazuyuki; Romero, Maria E; Virmani, Renu

    2016-01-01

    Inflammatory diseases of the aorta broadly include noninfectious and infectious aortitis, periaortitis, atherosclerosis, and inflammatory atherosclerotic aneurysms. Aortitis is uncommon but is increasingly recognized as an important cause of aortic aneurysms and dissections. Abdominal (AAA) and thoracic aortic aneurysms (TAA) have different pathologies and etiologies. AAAs are the most common type of aortic aneurysm, and the vast majority of these are atherosclerotic. The causes of TAA vary depending on the site of involvement, but medial degeneration is a common pathologic substrate, regardless of etiology, and genetic influences play a prominent role in TAA expression. Standardized classification schemes for inflammatory and degenerative diseases of the aorta have only recently been added to the pathology literature. A brief overview of the new histopathologic classifications for aortic inflammatory and degenerative diseases has recently been published by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology as a consensus document on the surgical pathology of the aorta. Vascular calcification is a highly regulated biologic process, and the mechanisms leading to vascular calcification are under investigation. Calcification may occur in the intima (atherosclerotic) or in the media secondary to metabolic disease. Rarely, vascular calcification may be associated with genetic disorders. PMID:27526100

  12. Outcomes and safety of percutaneous aortic valve replacement.

    PubMed

    Zajarias, Alan; Cribier, Alain G

    2009-05-19

    The concept of transcatheter aortic valve replacement was developed with the goal of offering a therapeutic solution to patients with severe symptomatic aortic stenosis who are not considered good candidates for surgical valve replacement. Initial attempts were complicated by vascular access problems and lack of appropriate tools. With time and experience, early problems were solved and the concepts of valve sizing, valve positioning, and patient selection were defined. Technological improvements allowed the use of smaller arterial sheaths to decrease vascular trauma, special catheters to facilitate valve delivery, and treatments on the valve prostheses that would ensure longer durability. After 5 years, the number of transcatheter aortic valve replacements has grown significantly, and will likely continue as this technology becomes increasingly available. Currently, 2 valve models, the Edwards SAPIEN valve (Edwards Lifescience, Irvine, California) and the CoreValve ReValving system (CoreValve Inc., Irvine, California), have been used in over 4,000 cases worldwide for the treatment of symptomatic aortic stenosis. Midterm follow-up shows no evidence of restenosis or prosthetic valve dysfunction. Transfemoral and transapical delivery routes can be selected depending on the quality of vascular access and the type of prosthesis used. Randomized trials that are currently underway will confirm procedural safety and guide the applicability of this technology.

  13. Transcatheter aortic valve implantation in Jehovah's Witness patients with symptomatic severe aortic valve stenosis

    PubMed Central

    Buz, Semih; Pasic, Miralem; Unbehaun, Axel; Hetzer, Roland

    2012-01-01

    Transcatheter aortic valve implantation (TAVI) is currently reserved for high or prohibitive surgical-risk patients with aortic valve stenosis. We report on successful TAVI in two Jehovah's witness patients. It offers a simple and effective treatment of severe aortic valve stenosis in high-risk patients who refuse the use of allogeneic blood and blood products. PMID:22753437

  14. Contemporary management of aortic stenosis: surgical aortic valve replacement remains the gold standard.

    PubMed

    Walther, Thomas; Blumenstein, Johannes; van Linden, Arnaud; Kempfert, Jörg

    2012-11-01

    Aortic valve disease is the most frequent acquired heart valve lesion in humans. In western communities, approximately 90% of patients present with aortic stenosis (AS), predominantly of a calcific degenerative aetiology. The remaining approximately 10% of patients predominantly present with aortic valve incompetence.

  15. Cervical aortic arch and a new type of double aortic arch. Report of a case.

    PubMed Central

    Cornali, M; Reginato, E; Azzolina, G

    1976-01-01

    A case of cervical aortic arch is reported. To the best of our knowledge, it is the first to be associated with a serious intracardiac anomaly. In addition, it is part of a new type of double aortic arch, caused by failure of reabsorption of both dorsal aortic roots and persistence of the fourth right and second (or third) left branchial arches. PMID:971387

  16. Aortic Valve Surgery: Minimally Invasive Options

    PubMed Central

    Ramlawi, Basel; Bedeir, Kareem; Lamelas, Joseph

    2016-01-01

    Minimally invasive aortic valve surgery has not been adopted by a significant proportion of cardiac surgeons despite proven benefits. This may be related to a high learning curve and technical issues requiring retraining. In this review, we discuss the data for minimally invasive aortic valve surgery and describe our operative technique for both ministernotomy and anterior thoracotomy approaches. We also discuss the advent of novel sutureless valves and how these techniques compare to available transcatheter aortic valve procedures. PMID:27127559

  17. Genetic variation in MDR1, LPL and eNOS genes and the response to atorvastatin treatment in ischemic stroke.

    PubMed

    Munshi, Anjana

    2012-11-01

    Statins reduce the risk of cardiovascular events by lowering the blood cholesterol. Many genes involved in the pharmacodynamic pathway of statins have been part of pharmacogenetic research in patients with hypercholesterolemia, with an emphasis on genes involved in the cholesterol pathway. The present study was carried out with an aim to evaluate the association between the genetic variants of lipoprotein lipase gene [HindIII (+/+)/HindIII (-/-)], multiple drug resistance gene (C3435T) and endothelial nitric oxide synthase gene (4a/4b) with clinical outcome including an increased risk of recurrent stroke or death in ischemic stroke patients on atorvastatin therapy. 525 stroke patients and 500 healthy controls were involved in the study. Follow-up telephone interviews were conducted with patients post-event to determine stroke outcome. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. A significant association of MDR1 and LPL gene variants with bad outcome in stroke patients on atorvastatin therapy was found. However, there was no significant association of 27 bp VNTR polymorphism of eNOS gene with outcome. MDR analysis was carried out to analyze gene-gene interaction involving these gene variants contributing to clinical outcome of patients on stratin therapy but no significant interaction between these variants was observed. In conclusion the individuals with HindIII (-/-) genotype of LPL and CC genotype of MDR1 gene would benefit more from atorvastatin therapy. PMID:22810051

  18. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    PubMed

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

  19. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study

    PubMed Central

    Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Corte, Cristina della; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena

    2016-01-01

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

  20. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    PubMed

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib.

  1. Quantification of biomechanical interaction of transcatheter aortic valve stent deployed in porcine and ovine hearts.

    PubMed

    Mummert, Joseph; Sirois, Eric; Sun, Wei

    2013-03-01

    Success of the deployment and function in transcatheter aortic valve replacement is heavily reliant on the tissue-stent interaction. The present study quantified important tissue-stent contact variables of self-expanding transcatheter aortic valve stents when deployed into ovine and porcine aortic roots, such as the stent radial expansion force, stent pullout force, the annulus deformation response and the coefficient of friction on the tissue-stent contact interface. Braided Nitinol stents were developed, tested to determine stent crimped diameter vs. stent radial force from a stent crimp experiment, and deployed in vitro to quantify stent pullout, aortic annulus deformation, and the coefficient of friction between the stent and the aortic tissue from an aortic root-stent interaction experiment. The results indicated that when crimped at body temperature from 26 mm to 19, 21 and 23 mm stent radial forces were approximately 30-40% higher than those crimped at room temperature. Coefficients of friction leveled to approximately 0.10 ± 0.01 as stent wire diameter increased and annulus size decreased from 23 to 19 mm. Regardless of aortic annulus size and species tested, it appeared that a minimum of about 2.5 mm in annular dilatation, caused by about 60 N of radial force from stent expansion, was needed to anchor the stent against a pullout into the left ventricle. The study of the contact biomechanics in animal aortic tissues may help us better understand characteristics of tissue-stent interactions and quantify the baseline responses of non-calcified aortic tissues.

  2. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice

    PubMed Central

    Miller, Jordan D.; Weiss, Robert M.; Serrano, Kristine M.; Brooks, Robert M.; Berry, Christopher J.; Zimmerman, Kathy; Young, Stephen G.; Heistad, Donald D.

    2009-01-01

    Background Treatment of hyperlipidemia produces functional and structural improvements in atherosclerotic vessels. However, the effects of treating hyperlipidemia on the structure and function of the aortic valve has been controversial, and any effects could be confounded by pleiotropic effects of hypolipidemic treatment. The goal of this study was to determine whether reducing elevated plasma lipid levels with a “genetic switch” in Reversa mice (Ldlr−/−/Apob100/100/Mttpfl/fl/Mx1Cre+/+) reduces oxidative stress, reduces proosteogenic signaling, and retards the progression of aortic valve disease. Methods and Results After 6 months of hypercholesterolemia, Reversa mice exhibited increases in superoxide, lipid deposition, myofibroblast activation, calcium deposition, and pro-osteogenic protein expression in the aortic valve. Maximum aortic valve cusp separation, as judged by echocardiography, was not altered. During an additional 6 months of hypercholesterolemia, superoxide levels, valvular lipid deposition, and myofibroblast activation remained elevated. Furthermore, calcium deposition and pro-osteogenic gene expression became more pronounced and the aortic cusp separation decreased from 0.85 ± 0.04 to 0.70 ± 0.04 mm (mean ± SE; p < 0.05). Rapid normalization of cholesterol levels at 6 months of age (by inducing expression of Cre recombinase) normalized aortic valve superoxide levels, decreased myofibroblast activation, reduced valvular calcium burden, suppressed pro-osteogenic signaling cascades, and prevented the reductions in aortic valve cusp separation. Conclusions Collectively, these data indicate that reducing plasma lipid levels by genetic inactivation of the mttp gene in hypercholesterolemic mice with early aortic valve disease normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of aortic valve stenosis. PMID:19433756

  3. Aortic root dilatation in young men with normally functioning bicuspid aortic valves

    PubMed Central

    Nistri, S; Sorbo, M; Marin, M; Palisi, M; Scognamiglio, R; Thiene, G

    1999-01-01

    OBJECTIVE—To evaluate the dimensions of the aortic root in a selected population of young males with isolated normally functioning bicuspid aortic valve.
DESIGN AND SETTING—Echocardiographic and Doppler evaluation of conscripts with bicuspid aortic valve at the time of military pre-enrolment screening in two military hospitals.
SUBJECTS AND METHODS—66 consecutive young men with a normally functioning bicuspid aortic valve were studied to assess aortic size at four aortic levels: annulus, sinuses of Valsalva, supra-aortic ridge, and proximal ascending aorta; 70 consecutive normal young subjects, matched for age and body surface area, were used as controls.
RESULTS—In men with a bicuspid aortic valve, the diameter of the aortic root was significantly larger than in controls at the sinuses (3.16 (0.37) v 2.87 (0.31) cm, p < 0.001), at the supra-aortic ridge (2.64 (0.46) v 2.47 (0.28) cm, p = 0.01), and at the level of the proximal ascending aorta (3.12 (0.48) v 2.69 (0.28) cm, p < 0.001). The prevalence of aortic root dilatation was 7.5% at the annulus (5/66), 19.6% at the sinuses (13/66), 15% at the supra-aortic ridge (10/66), and 43.9% at the ascending aorta (29/66); 32 subjects (48%) had aortic root dimensions comparable with controls, while 34 (52%) had definitely abnormal aortic root dimensions.
CONCLUSIONS—Aortic root enlargement in people with a bicuspid aortic valve occurs independently of haemodynamic abnormalities, age, and body size. However, there appear to be different subgroups of young adults with bicuspid aortic valves, one of which is characterised by aortic dilatation, possibly caused by a congenital abnormality of the aortic wall.


Keywords: bicuspid aortic valve; aortic root dilatation PMID:10377302

  4. Aortic root surgery in combination with hypothermic circulatory arrest: preserve or replace the aortic valve in the context of postoperative neurological outcome? A case match comparison.

    PubMed

    Khaladj, Nawid; Ismail, Issam; Shrestha, Malakh; Peterss, Sven; Pichlmaier, Maximilian; Kallenbach, Klaus; Haverich, Axel; Hagl, Christian

    2009-08-01

    The objective of this study was to compare the results of elective composite (C) vs. David (D) operations in patients requiring additional aortic arch surgery using hypothermic circulatory arrest (HCA) and selective antegrade cerebral perfusion (SACP), with the focus on postoperative neurological outcome and quality of life (SF-36). Between November 1999 and March 2006, 333 patients underwent aortic root surgery and ascending aortic replacement with HCA and SACP at our institution. Out of these patients, 46 were matched with respect to age, gender, HCA-time and year of surgery. Two patients, one in each group, died during hospital stay (4%), with no late deaths. Follow-up was completed in 95% [64 (6-90) months]. Cardiopulmonary bypass (CPB) time (141 min vs. 168 min, P=0.007) and aortic cross-clamp time (99 min vs. 123 min, P=0.004) were significantly longer in the David-group. The incidence of temporary neurological dysfunction (TND 7%: D n=1, C n=2) was not different between groups, no permanent dysfunction could be detected. Follow-up SF-36 scores were comparable. The combination of aortic arch surgery with more time consuming valve sparing aortic root surgery does not increase the risk for adverse outcome applying comparable periods of HCA and SACP.

  5. Endovascular repair of a right-sided descending thoracic aortic aneurysm associated with a right aortic arch and a left subclavian artery arising from a Kommerell's diverticulum.

    PubMed

    Klonaris, Chris; Avgerinos, Efthimios D; Katsargyris, Athanasios; Matthaiou, Alexandros; Georgopoulos, Sotirios; Psarros, Vasileios; Bastounis, Elias

    2009-07-01

    This case report describes the endovascular repair of a right-sided descending thoracic aortic aneurysm associated with a right aortic arch and an aberrant left subclavian artery. A 76-year-old male with multiple comorbidities was incidentally found to have a right-sided descending thoracic aortic aneurysm with a maximum diameter of 6.2 cm. Additionally, there was a right aortic arch with a retroesophageal segment and separate arch branches arising in the following order: left common carotid artery, right common carotid artery, right subclavian artery, and left subclavian artery that was aberrant, arising from a Kommerrell's diverticulum. The aneurysm was successfully excluded by deployment of a Zenith TX1 36 x 32 x 20-mm stent-graft using wire traction technique via the left femoral and right brachial arteries in order to deal with two severe aortic angulations. At 18-month follow-up the patient was doing well, with aneurysm sac shrinkage to 5.9 cm and no signs of endoleak or migration. Endovascular repair of right-sided descending thoracic aortic aneurysms with a right arch and aberrant left subclavian artery is feasible, safe, and effective. In such rare configurations, which demand considerably increased technical dexterity and center experience, endovascular repair emerges as an attractive therapeutic option.

  6. Endovascular Repair of a Right-Sided Descending Thoracic Aortic Aneurysm Associated with a Right Aortic Arch and a Left Subclavian Artery Arising from a Kommerell's Diverticulum

    SciTech Connect

    Klonaris, Chris Avgerinos, Efthimios D.; Katsargyris, Athanasios; Matthaiou, Alexandros; Georgopoulos, Sotirios; Psarros, Vasileios; Bastounis, Elias

    2009-07-15

    This case report describes the endovascular repair of a right-sided descending thoracic aortic aneurysm associated with a right aortic arch and an aberrant left subclavian artery. A 76-year-old male with multiple comorbidities was incidentally found to have a right-sided descending thoracic aortic aneurysm with a maximum diameter of 6.2 cm. Additionally, there was a right aortic arch with a retroesophageal segment and separate arch branches arising in the following order: left common carotid artery, right common carotid artery, right subclavian artery, and left subclavian artery that was aberrant, arising from a Kommerrell's diverticulum. The aneurysm was successfully excluded by deployment of a Zenith TX1 36 x 32 x 20-mm stent-graft using wire traction technique via the left femoral and right brachial arteries in order to deal with two severe aortic angulations. At 18-month follow-up the patient was doing well, with aneurysm sac shrinkage to 5.9 cm and no signs of endoleak or migration. Endovascular repair of right-sided descending thoracic aortic aneurysms with a right arch and aberrant left subclavian artery is feasible, safe, and effective. In such rare configurations, which demand considerably increased technical dexterity and center experience, endovascular repair emerges as an attractive therapeutic option.

  7. Giant Aortic Root Aneurysm Presenting as Acute Type A Aortic Dissection.

    PubMed

    Raz, Guy M; Stamou, Sotiris C

    2014-06-01

    A 49-year-old woman with four months of increasing episodic palpitations, chest pain, and shortness of breath presented to an outside clinic where a new 4/6 systolic ejection murmur was identified. A transthoracic echocardiogram revealed a large aortic root aneurysm. The patient underwent emergent repair of the dissected root aneurysm with a modified Bentall procedure utilizing a #19 St Jude Valsalva mechanical valve conduit. Postoperatively, she required a permanent pacemaker placement. Her echo showed ejection fraction improvement from a preoperative 25% to a postoperative 35%. She was discharged home on postoperative day 7. PMID:26798728

  8. Hybrid treatment of penetrating aortic ulcer.

    PubMed

    Lara, Juan Antonio Herrero; Martins-Romêo, Daniela de Araújo; Escudero, Carlos Caparrós; Vázquez, Rosa María Lepe; Falcón, María Del Carmen Prieto; Batista, Vinicius Bianchi

    2015-01-01

    Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

  9. Low-gradient aortic stenosis.

    PubMed

    Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

    2016-09-01

    An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS.

  10. Endothelio-mesenchymal interaction controls runx1 expression and modulates the notch pathway to initiate aortic hematopoiesis

    PubMed Central

    Richard, Charlotte; Drevon, Cécile; Canto, Pierre-Yves; Villain, Gaelle; Bollérot, Karine; Lempereur, Aveline; Teillet, Marie-Aimée; Vincent, Christine; Castillo, Catalina Rosselló; Torres, Miguel; Piwarzyk, Eileen; Speck, Nancy A.; Souyri, Michèle; Jaffredo, Thierry

    2014-01-01

    SUMMARY Hematopoietic stem cells (HSCs) are produced by a small cohort of hemogenic endothelial cells (ECs) during development through the formation of intra-aortic hematopoietic cell (HC) clusters (HCs). The Runx1 transcription factor plays a key role in the EC to HC and HSC transition. We show that Runx1 expression in hemogenic ECs and the subsequent initiation of HC formation are tightly controlled by the sub-aortic mesenchyme, although the mesenchyme is not a source of HCs. Runx1 and Notch signaling are involved in this process, with Notch signaling decreasing with time in HCs. Inhibiting Notch signaling readily increases HC production in mouse and chicken embryos. In the mouse however, this increase is transient. Collectively, we show complementary roles of hemogenic ECs and mesenchymal compartments in triggering aortic hematopoiesis. The sub-aortic mesenchyme induces Runx1 expression in hemogenic-primed endothelial cells and collaborates with Notch dynamics to control aortic hematopoiesis. PMID:23537631

  11. The hemodynamic effects of acute aortic regurgitation into a stiffened left ventricle resulting from chronic aortic stenosis.

    PubMed

    Okafor, Ikechukwu; Raghav, Vrishank; Midha, Prem; Kumar, Gautam; Yoganathan, Ajit

    2016-06-01

    Acute aortic regurgitation (AR) post-chronic aortic stenosis is a prevalent phenomenon occurring in patients who undergo transcatheter aortic valve replacement (TAVR) surgery. The objective of this work was to characterize the effects of left ventricular diastolic stiffness (LVDS) and AR severity on LV performance. Three LVDS models were inserted into a physiological left heart simulator. AR severity was parametrically varied through four levels (ranging from trace to moderate) and compared with a competent aortic valve. Hemodynamic metrics such as average diastolic pressures (DP) and reduction in transmitral flow were measured. AR index was calculated as a function of AR severity and LVDS, and the work required to make up for lost volume due to AR was estimated. In the presence of trace AR, higher LVDS had up to a threefold reduction in transmitral flow (13% compared with 3.5%) and a significant increase in DP (2-fold). The AR index ranged from ∼42 to 16 (no AR to moderate AR), with stiffer LVs having lower values. To compensate for lost volume due to AR, the low, medium, and high LVDS models were found to require 5.1, 5.5, and 6.6 times more work, respectively. This work shows that the LVDS has a significant effect on the LV performance in the presence of AR. Therefore, the LVDS of potential TAVR patients should be assessed to gain an initial indication of their ability to tolerate post-procedural AR. PMID:27106040

  12. eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

    PubMed Central

    Li, Feng; Hagaman, John R.; Kim, Hyung-Suk; Maeda, Nobuyo; Jennette, J. Charles; Faber, James E.; Karumanchi, S. Ananth; Smithies, Oliver

    2012-01-01

    Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia–like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia–like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467±74 versus 174±23 μg/d), lower creatinine clearance (126±29 versus 452±63 μl/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ETA receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ETA receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia–like phenotype through activation of the endothelin system. PMID:22282588

  13. Possible involvement of PPARγ-associated eNOS signaling activation in rosuvastatin-mediated prevention of nicotine-induced experimental vascular endothelial abnormalities.

    PubMed

    Kathuria, Sonam; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-02-01

    Nicotine exposure via cigarette smoking and tobacco chewing is associated with vascular complications. The present study investigated the effect of rosuvastatin in nicotine (2 mg/kg/day, i.p., 4 weeks)-induced vascular endothelial dysfunction (VED) in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating aortic and serum nitrite/nitrate concentration. Further, scanning electron microscopy and hematoxylin-eosin staining of thoracic aorta were performed to assess the vascular endothelial integrity. Moreover, oxidative stress was assessed by estimating aortic superoxide anion generation and serum thiobarbituric acid-reactive substances. The nicotine administration produced VED by markedly reducing acetylcholine-induced endothelium-dependent relaxation, impairing the integrity of vascular endothelium, decreasing aortic and serum nitrite/nitrate concentration, increasing oxidative stress, and inducing lipid alteration. However, treatment with rosuvastatin (10 mg/kg/day, i.p., 4 weeks) markedly attenuated nicotine-induced vascular endothelial abnormalities, oxidative stress, and lipid alteration. Interestingly, the co-administration of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 (1 mg/kg/day, i.p., 2 weeks) submaximally, significantly prevented rosuvastatin-induced improvement in vascular endothelial integrity, endothelium-dependent relaxation, and nitrite/nitrate concentration in rats administered nicotine. However, GW9662 co-administration did not affect rosuvastatin-associated vascular anti-oxidant and lipid-lowering effects. The incubation of aortic ring, isolated from rosuvastatin-treated nicotine-administered rats, with L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), significantly attenuated rosuvastatin-induced improvement in acetylcholine-induced endothelium-dependent relaxation. Rosuvastatin prevents nicotine-induced vascular endothelial abnormalities by activating

  14. Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid: Implications for Aortic Dissection.

    PubMed

    Mallat, Ziad; Tedgui, Alain; Henrion, Daniel

    2016-09-01

    The pathophysiology of aortic dissection is poorly understood, and its risk is resistant to medical treatment. Most studies have focused on a proposed pathogenic role of transforming growth factor-β in Marfan disease and related thoracic aortic aneurysms and aortic dissections. However, clinical testing of this concept using angiotensin II type 1 receptor antagonists to block transforming growth factor-β signaling fell short of promise. Genetic mutations that predispose to thoracic aortic aneurysms and aortic dissections affect components of the extracellular matrix and proteins involved in cellular force generation. Thus, a role for dysfunctional mechanosensing in abnormal aortic wall remodeling is emerging. However, how abnormal mechanosensing leads to aortic dissection remains a mystery. Here, we review current knowledge about the regulation of interstitial fluid dynamics and myogenic tone and propose that alteration in contractile force reduces vascular tone in the microcirculation (here, aortic vasa vasorum) and leads to elevations of blood flow, transmural pressure, and fluid flux into the surrounding aortic media. Furthermore, reduced contractile force in medial smooth muscle cells coupled with alteration of structural components of the extracellular matrix limits extracellular matrix contraction, further promoting the formation of intramural edema, a critical step in the initiation of aortic dissection. The concept is supported by several pathophysiological and clinical observations. A direct implication of this concept is that drugs that lower blood pressure and limit interstitial fluid accumulation while preserving or increasing microvascular tone would limit the risk of dissection. In contrast, drugs that substantially lower microvascular tone would be ineffective or may accelerate the disease and precipitate aortic dissection. PMID:27444198

  15. Disturbance effects of PM₁₀ on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid.

    PubMed

    Dianat, Mahin; Radmanesh, Esmat; Badavi, Mohammad; Mard, Seyed Ali; Goudarzi, Gholamraza

    2016-03-01

    Myocardial infarction is the acute condition of myocardial necrosis that occurs as a result of imbalance between coronary blood supply and myocardial demand. Air pollution increases the risk of death from cardiovascular diseases (CVDs). The aim of this study was to investigate the effects of particulate matter (PM) on oxidative stress, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) level induced by ischemia-reperfusion injury, and the protective effects of vanillic acid (VA) in the isolated rat heart. Male Wistar rats were randomly divided into eight groups (n = 10), namely control, VAc, sham, VA, PMa (0.5 mg/kg), PMb (2.5 mg/kg), PMc (5 mg/kg), and PMc + VA groups. Particles with an aerodynamic diameter <10 μm (PM10) was instilled into the trachea through a fine intubation tube. Two days following the PM10 instillation, the animal's hearts were isolated and transferred to a Langendorff apparatus. The hearts were subjected to 30 min of global ischemia followed by 60 min of reperfusion. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), xanthine oxidase (XOX), and lactate dehydrogenase (LDH) were measured using special kits. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine levels of iNOS and eNOS mRNA. An increase in left ventricular end-diastolic pressure (LVEDP), S-T elevation, and oxidative stress in PM10 groups was observed. Ischemia-reperfusion (I/R) induction showed a significant augment in the expression of iNOS mRNA level and a significant decrease in the expression eNOS mRNA level. This effect was more pronounced in the PM groups than in the control and sham groups. Vanillic acid caused a significant decrease in LVEDP, S-T elevation, and also a significant difference in eNOS mRNA expression level, antioxidant enzymes, iNOS mRNA expression level, and oxidative stress occurred on myocardial dysfunction

  16. Aortic root disease in athletes: aortic root dilation, anomalous coronary artery, bicuspid aortic valve, and Marfan's syndrome.

    PubMed

    Yim, Eugene Sun

    2013-08-01

    Two professional athletes in the U.S. National Basketball Association required surgery for aortic root dilation in 2012. These cases have attracted attention in sports medicine to the importance of aortic root disease in athletes. In addition to aortic root dilation, other forms of aortic disease include anomalous coronary artery, bicuspid aortic valve, and Marfan's syndrome. In this review, electronic database literature searches were performed using the terms "aortic root" and "athletes." The literature search produced 122 manuscripts. Of these, 22 were on aortic root dilation, 21 on anomalous coronary arteries, 12 on bicuspid aortic valves, and 8 on Marfan's syndrome. Aortic root dilation is a condition involving pathologic dilation of the aortic root, which can lead to life-threatening sequelae. Prevalence of the condition among athletes and higher risk athletes in particular sports needs to be better delineated. Normative parameters for aortic root diameter in the general population are proportionate to anthropomorphic variables, but this has not been validated for athletes at the extremes of anthropomorphic indices. Although echocardiography is the favored screening modality, computed tomography (CT) and cardiac magnetic resonance imaging (MRI) are also used for diagnosis and surgical planning. Medical management has utilized beta-blockers, with more recent use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and statins. Indications for surgery are based on comorbidities, degree of dilation, and rate of progression. Management decisions for aortic root dilation in athletes are nuanced and will benefit from the development of evidence-based guidelines. Anomalous coronary artery is another form of aortic disease with relevance in athletes. Diagnosis has traditionally been through cardiac catheterization, but more recently has included evaluation with echocardiography, multislice CT, and MRI. Athletes with this

  17. A numerical study of ENO and TVD schemes for shock capturing

    NASA Technical Reports Server (NTRS)

    Chang, Shih-Hung; Liou, Meng-Sing

    1988-01-01

    The numerical performance of a second-order upwind-based total variation diminishing (TVD) scheme and that of a uniform second-order essentially non-oscillatory (ENO) scheme for shock capturing are compared. The TVD scheme used is a modified version of Liou, using the flux-difference splitting (FDS) of Roe and his superbee function as the limiter. The construction of the basic ENO scheme is based on Harten, Engquist, Osher, and Chakravarthy, and the 2-D extensions are obtained by using a Strang-type of fractional-step time-splitting method. Numerical results presented include both steady and unsteady, 1-D and 2-D calculations. All the chosen test problems have exact solutions so that numerical performance can be measured by comparing the computer results to them. For 1-D calculations, the standard shock-tube problems of Sod and Lax are chosen. A very strong shock-tube problem, with the initial density ratio of 400 to 1 and pressure ratio of 500 to 1, is also used to study the behavior of the two schemes. For 2-D calculations, the shock wave reflection problems are adopted for testing. The cases presented in this report include flows with Mach numbers of 2.9, 5.0, and 10.0.

  18. 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

  19. PECAM-1 Isoforms, eNOS, and Endoglin Axis in Regulation of Angiogenesis

    PubMed Central

    Park, SunYoung; Sorenson, Christine M.; Sheibani, Nader

    2016-01-01

    Vascular development and maintenance of proper vascular function through various regulatory mechanisms are critical to our wellbeing. Delineating the regulatory processes involved in development of vascular system and function is one of the most important topics in human physiology and pathophysiology. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a cell adhesion molecule with proangiogenic and proinflammatory activity, has been subject of numerous studies. Here we will review the important roles PECAM-1 and its isoforms play during angiogenesis, and its molecular mechanisms of action in the endothelium. In the endothelium, PECAM-1 not only plays a role as an adhesion molecule but also participates in intracellular signaling pathways which impact various cell adhesive mechanisms and endothelial nitric oxide (eNOS) expression and activity. In addition, recent studies from our laboratory have revealed an important relationship between PECAM-1 and endoglin expression. Endoglin is an essential molecule during angiogenesis, vascular development and integrity whose expression and activity are compromised in the absence of PECAM-1. Here we will discuss the roles PECAM-1 isoforms may play in modulation of endothelial cell adhesive mechanisms, eNOS and endoglin expression and activity, and angiogenesis. PMID:25976664

  20. eNOS tag SNP haplotypes in hypertensive disorders of pregnancy.

    PubMed

    Muniz, Ludmila; Luizon, Marcelo R; Palei, Ana C T; Lacchini, Riccardo; Duarte, Geraldo; Cavalli, Ricardo C; Tanus-Santos, Jose E; Sandrim, Valeria C

    2012-12-01

    Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n=122), GH (n=138), and PE (n=157). The haplotype formed by "C b G G C" was more frequent in HP compared to GH and PE (p=0.0071), which is supported by previous findings that demonstrated the association of the combination "C b G" with a higher level of nitrite (NO marker). Our results suggest a protective effect of the haplotype "C b G G C" against the development of hypertensive disorders of pregnancy. PMID:23062210

  1. AKI after Transcatheter or Surgical Aortic Valve Replacement.

    PubMed

    Thongprayoon, Charat; Cheungpasitporn, Wisit; Srivali, Narat; Harrison, Andrew M; Gunderson, Tina M; Kittanamongkolchai, Wonngarm; Greason, Kevin L; Kashani, Kianoush B

    2016-06-01

    Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.

  2. Vascular Complications Associated with Transfemoral Aortic Valve Replacement.

    PubMed

    Hines, George L; Jaspan, Vita; Kelly, Brian J; Calixte, Rose

    2016-06-01

    Background Transfemoral aortic valve replacement (TAVR) is a novel technique for treating aortic stenosis, yet vascular complications are yet to be delineated. Objectives This study aims to study the vascular complications of TAVR with Edwards Sapien valves (Edwards Lifesciences Corp., Irvine, CA). Methods We performed a retrospective evaluation of TAVR patients. Standard demographics, femoral vessel and sheath size, access type (femoral cut-down [FC], percutaneous access [PFA], and iliac conduit [IC]), and treatment method were recorded. Complications were defined by the Valve Academic Research Consortium Criteria. Logistic regression was used for statistical analysis. Results A total of 99 patients underwent TAVR between February 15, 2012 and July 17, 2013 with an Edwards Sapien valve. Out of which, 48 were males with a mean age of 83 ± 7 years. Overall, 33 had FC, 58 had PFA, and 6 had an IC. A total of 17 major (2 aortic and 15 iliac) and 38 minor complications (36 access and 2 emboli) occurred. Aortic complications were managed by open repair (OR, 1) or percutaneous repair (PR, 1). Overall, 12 iliac injuries were managed by PR and 3 by OR. Out of the 33 groin complications in FC patients 8 (24%) were treated by OR, whereas 30 (52%) of the 58 groin complications in PTA patients were treated by PR. There were no differences in transfusion requirements or length of stay. Conclusion Vascular complications of TAVR are common with most being minor, related to access site and causing no immediate sequelae. Iliac injury can be managed by PR or OR. Aortic injury is associated with significant mortality. These findings increase vascular surgeons' awareness of these complications and how to manage them. PMID:27231425

  3. In vitro testing of a temporary catheter-based aortic "parachute" valve.

    PubMed

    Vandenberghe, Stijn; Salizzoni, Stefano; Bajona, Pietro; Zehr, Kenton J; Speziali, Giovanni

    2008-01-01

    Recently developed technologies allow aortic valve implantation off-pump in a beating heart. In this procedure, the native, stenotic aortic valve is not removed, but simply crushed by a pressure balloon mounted on a percutaneous catheter. Removal of the native aortic cusps before valve replacement may reduce the incidence of annular or cuspal calcium embolization and late perivalvular leaks and increase implantable valve size. However, a temporary valve system in the ascending aorta may be necessary to maintain hemodynamic stability by reducing acute aortic regurgitation and left ventricular volume overload. This study evaluates the hemodynamic effects of a wire-mounted, monoleaflet, temporary valve apparatus in a mechanical cardiovascular simulator. Aortic flow, systemic pressure and left ventricular pressure were continuously monitored. An intraluminal camera obtained real-time proximal and distal images of the valve in operation. Insertion of the parachute valve in the simulator increased diastolic pressure from 7 to 38 mm Hg. Cardiac output increased from 2.08 to 4.66 L/min and regurgitant volume decreased from 65 to 23 mL. In conclusion, placement of a temporary valve in the ascending aorta may help maintain hemodynamic stability and improve off-pump aortic valve replacement.

  4. WUnicuspid Aortic Valve- An Uncommon Anomaly With a Common Presentation.

    PubMed

    Sitwala, Puja; Abusara, Ashraf; Ladia, Vatsal; Ladia, Vatsal; Panchal, Hemang B; Raudat, Charles; Paul, Timir K

    2016-01-01

    Unicuspid aortic valve (UAV), which is a rare congenital anomaly, usually presents as aortic stenosis and/or aortic regurgitation. Here we present a case of UAV co-existent with an ascending aortic aneurysm. A 26-year-old male with no significant past medical history presented to the hospital after two episodes of syncope. Transthoracic echocardiogram showed an ejection fraction of 62%, severely stenotic aortic valve, and moderate aortic regurgitation. Computed tomography revealed calcification of the aortic valve, compatible with aortic stenosis and aneurysm of the ascending aorta measuring 4.3 cm in diameter. He underwent successful aortic valve replacement and repair of ascending aortic aneurysm. He recovered well without any complications. This case suggests that any young patient who presents with syncope, aortic stenosis would be a differential and further workup by any available non-invasive modality needs to be performed.

  5. [Surgical aspects of acute aortic dissection].

    PubMed

    Laas, J; Heinemann, M; Jurmann, M; Borst, H G

    1992-12-01

    This paper highlights some of the surgical aspects of acute aortic dissections such as: emergency diagnosis, indications for surgery, reconstructive operative techniques, malperfusion phenomena and necessity for follow-up. Aortic dissection is caused by an intimal tear, called the "entry", and subsequent splitting of the media by the stream of blood. Two lumina are thus created, which may communicate through "re-entries". As this creates severe weakness of the aortic wall, rupture and/or dilatation are the imminent dangers of acute aortic dissection. Acute aortic dissection type A, by definition involving the ascending aorta (Figures 1 and 2), is an absolute indication for emergency surgical treatment, because its natural history shows an extremely poor outcome (Figure 3). Due to impending (intrapericardial) aortic rupture, it may be necessary to limit diagnostic procedures to a minimum. Transesophageal echocardiography is the method of choice for establishing a quick, precise and reliable diagnosis (Figure 4). In stable patients, computed tomography gives additional information about aortic diameters or sites of extrapericardial perforation. Digital subtraction angiography (DSA) shows perfusion of the lumina and dependent organs. The surgical strategy in acute aortic dissection type A aims at replacement of the ascending aorta. Reconstructive techniques have to be considered, especially in aortic valve regurgitation without annuloectasia (Figures 5 and 6). In recent times, the use of GRF tissue glue has reduced the need for teflon felt. Involvement of the aortic arch should be treated aggressively up to the point of total arch replacement in deep hypothermic circulatory arrest as part of the primary procedure (Figure 7). Malperfusion phenomena of aortic branches remain risk-factors.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Congenital quadricuspid aortic valve associated with aortic insufficiency and mitral regurgitation

    PubMed Central

    2013-01-01

    Congenital quadricuspid aortic valve is a rare cardiac anomaly. More than half of the patients with this abnormality will develop aortic insufficiency in adulthood. It is vital that patients with quadricuspid aortic valve who present with progressive aortic regurgitation undergo valve replacement or repair at appropriate time. Here, we present two cases of quadricuspid aortic valve. We first describe a 58-year-old man who had mitral regurgitation and ascending aorta dilatation with quadricuspid aortic valve. He underwent aortic valve replacement and mitral valve plasty and recovered well. The second patient is a 20-year-old asymptomatic boy who has been closely followed up and has not received any surgical treatment. PMID:23587156

  7. Congenital quadricuspid aortic valve associated with aortic insufficiency and mitral regurgitation.

    PubMed

    Zhu, Jiaquan; Zhang, Junwen; Wu, Shubin; Zhang, Yunjiao; Ding, Fangbao; Mei, Ju

    2013-01-01

    Congenital quadricuspid aortic valve is a rare cardiac anomaly. More than half of the patients with this abnormality will develop aortic insufficiency in adulthood. It is vital that patients with quadricuspid aortic valve who present with progressive aortic regurgitation undergo valve replacement or repair at appropriate time. Here, we present two cases of quadricuspid aortic valve. We first describe a 58-year-old man who had mitral regurgitation and ascending aorta dilatation with quadricuspid aortic valve. He underwent aortic valve replacement and mitral valve plasty and recovered well. The second patient is a 20-year-old asymptomatic boy who has been closely followed up and has not received any surgical treatment. PMID:23587156

  8. Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177

    PubMed Central

    Carneiro, Fernando S.; Giachini, Fernanda R.C.; Carneiro, Zidonia N.; Lima, Victor V.; Ergul, Adviye; Webb, R. Clinton; Tostes, Rita C.

    2011-01-01

    Introduction Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90–95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED. Aim Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability. Methods Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured. Main Outcome Measure GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein. Results GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages. Conclusion Although GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due

  9. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions.

    PubMed

    Ghosh, Suparna; Lakshmanan, Arun P; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R; Ding, Hong

    2015-12-01

    The cellular mechanisms whereby metformin, the first line drug for type 2 diabetes (T2DM), mediates its antidiabetic effects remain elusive, particularly as to whether metformin has a direct protective action on the vasculature. This study was designed to determine if a brief 3-h exposure to metformin protects endothelial function against the effects of hyperglycaemia. We investigated the protective effects of metformin on endothelial-dependent vasodilatation (EDV) in thoracic aortae from T2DM db/db mice and on high glucose (HG, 40 mM) induced changes in endothelial nitric oxide synthase (eNOS) signaling in mouse microvascular endothelial cells (MMECs) in culture. Exposure of aortae from db+/? non-diabetic control mice to high glucose (HG, 40 mM) containing Krebs for 3-h significantly (P<0.05) reduced acetylcholine (ACh)-induced EDV compared to ACh-induced EDV in aortae maintained in normal glucose (NG, 11 mM) Krebs. The reduction of EDV was partially reversed following a 3-h exposure to 50 μM metformin; metformin also improved ACh-induced EDV in aortae from diabetic db/db mice. Immunoblot analysis of MMECs cultured in HG versus NG revealed a significant reduction of the ratio of phosphorylated (p-eNOS)/eNOS and p-Akt/Akt, but not the expression of total eNOS or Akt. The 3-h exposure of MMECs to metformin significantly (P<0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1. Our data indicate that a 3-h exposure to metformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt.

  10. Quantitative Doppler-Echocardiographic Determination of Regurgitant Volume in Patients with Aortic Insufficiency

    PubMed Central

    Schoenhagen, Paul; Drude, Ludwig; Klein, Hermann H; Garcia, Mario J

    2008-01-01

    Background: The severity of aortic regurgitation (AR) can be determined by invasive or echocardiographic methods. We systematically compared quantitative invasive and echocardiographic data with semiquantitative invasive grades in a prospective series of patients. Methods: Using Doppler-echocardiography we determined the cardiac output over the aortic, pulmonary and mitral valve in 27 patients (20 with, 7 without AR). Aortic regurgitant volume was calculated as the difference between the cardiac output over aortic and pulmonary valve/ mitral valve. During angiography the severity of AR was assessed semiquantitatively by aortography and the regurgitant volume was calculated invasively as the difference between the left- and right ventricular cardiac output. Results: The echocardiographically and invasively determined regurgitant blood volume correlated closely (R≈0.8). The regurgitant volume increased with higher angiographic grade but there was significant overlap between adjoining qualitative grades. Conclusion: In patients with AR, quantitative echocardiographic and angiographic measurements of the regurgitant volume correlate closely. PMID:19590613

  11. 3D multislice CT angiography in post-aortic stent grafting: a pictorial essay.

    PubMed

    Sun, Zhonghua

    2006-01-01

    Helical CT angiography has been widely used in both pre- and post-aortic stent grafting and it has been confirmed to be the preferred modality when compared to conventional angiography. The recent development of multislice CT (MSCT) has further enhanced the applications of CT angiography for aortic stent grafting. One of the advantages of MSCT angiography over conventional angiography is that the 3D reconstructions, based on the volumetric CT data, provide additional information during follow-up of aortic stent grafting. While endovascular repair has been increasingly used in clinical practice, the use of 3D MSCT imaging in endovascular repair continues to play an important role. In this pictorial essay, we aimed to discuss the diagnostic performance of 3D MSCT angiography in post aortic stent grafting, including the most commonly used surface shaded display, curvilinear reformation, the maximum intensity projection, volume rendering and virtual endoscopy. The advantages and disadvantages of each 3D reconstruction are also explored.

  12. Bicuspid Aortic Cusp Fusion Morphology Alters Aortic 3D Outflow Patterns, Wall Shear Stress and Expression of Aortopathy

    PubMed Central

    Mahadevia, Riti; Barker, Alex J; Schnell, Susanne; Entezari, Pegah; Kansal, Preeti; Fedak, Paul W.M.; Malaisrie, S Chris; McCarthy, Patrick; Collins, Jeremy; Carr, James; Markl, Michael

    2014-01-01

    Background: Aortic 3D blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy. Methods and Results: 4D flow MRI measured in vivo 3D blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4mm; n=15 RN-BAV, 39.6±7.2mm); aorta size controls with tricuspid aortic valves (n=30, 41.1±4.4mm); healthy volunteers (n=15, 24.9±3.0mm). Aortopathy type (0-3), systolic flow angle, flow displacement, and regional wall shear stress (WSS) were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional WSS (p<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV compared to aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV were associated with altered flow displacement in the proximal and mid AAo for type 1 (42-81% decrease versus type 2) and distal AAo for type 3 (33-39% increase versus type 2). Conclusions: The presence and type of BAV fusion was associated with changes in regional WSS distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiologic mechanism by which valve morphology phenotype can influence phenotypes of BAV aortopathy. PMID:24345403

  13. Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis

    PubMed Central

    Cartlidge, Timothy R.G.; Jenkins, William S.A.; Adamson, Philip D.; Robson, Phillip; Lucatelli, Christophe; Van Beek, Edwin J.R.; Prendergast, Bernard; Denison, Alan R.; Forsyth, Laura; Rudd, James H.F.; Fayad, Zahi A.; Fletcher, Alison; Tuck, Sharon; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Background— 18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan–rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging. Methods and Results— Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan–rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias −0.05, limits of agreement −0·20 to +0·11). Conclusions— Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026. PMID:27733431

  14. The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

    PubMed Central

    2015-01-01

    Aims To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. Methods and results The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Conclusion Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. Clinical trial registration: ISRCTN 48334791. PMID:25627357

  15. Anesthetic management for resection of para-aortic paraganglioma and unexpected aortic resection: A case report

    PubMed Central

    WANG, CHERYL; RICHMOND, ROBERT; ELDESOUKI, ENAS

    2015-01-01

    Paragangliomas account for 15–20% of pheochromocytomas derived from chromaffin cells and secretes catecholamines. It has a high mortality rate due to hypertension and challenging anesthetic management. The present report is of a case of the successful management of paraganglioma resection with unexpected aortic resection. The patient presented for paraganglioma resection. The blood pressure (BP) was well controlled with α blockade followed by β blockade prior to surgery. The patient was under general anesthesia, with multiple intravenous lines, catheters and an arterial line. Induction was achieved by the administration of narcotic and volatile agents. During the procedure, the aorta was found to require resection in order to complete the tumor resection. The BP changed markedly with clamping and unclamping, tumor vein ligation and tumor resection. The increased BP due to catecholamine release and unclamping was controlled with phentolamine, nitroprusside, esmolol and labetolol. Drops in BP due to tumor vein ligation and clamping were managed with norepinephrine and vasopressin. With close communication and monitoring, the surgery on the patient was successfully completed and the patient was discharged days later in a hemodynamically stable condition. The diagnosis was further confirmed by pathology. This was a challenging case of paraganglioma resection with unexpected aortic resection. The success achieved suggests that the resection of paraganglioma and an aortic segment requires delicate anesthetic management. The key are α blockade and β blockade as necessary to control BP pre-operatively, frequent communication between the anesthesiologist and surgeons, intra-operative intervention in excess catecholamine release with phentolamine, nitroprusside and labetalol prior to tumor removal, and vasopressin for catecholamine deficiency when clamping or subsequent to tumor removal. It is a delicately orchestrated process requiring team work. PMID:25780466

  16. Recent advances in aortic valve replacement for aortic stenosis

    PubMed Central

    Al-Adhami, Ahmed; Al-Attar, Nawwar

    2016-01-01

    Aortic valve replacement is no longer an operation that is approached solely through a median sternotomy. Recent advances in the fields of transcatheter valves have expanded the proportion of patients eligible for intervention. Comparisons between transcatheter valves and conventional surgery have shown non-inferiority of transcatheter valve implants in patients with a high or intermediate pre-operative predictive risk. With advances in our understanding of sutureless valves and their applicability to minimally invasive surgery, the invasiveness and trauma of surgery can be reduced with potential improvements in outcome. The strategy of care has radically changed over the last decade. PMID:27803800

  17. Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes

    PubMed Central

    Raaz, Uwe; Schellinger, Isabel N.; Chernogubova, Ekaterina; Warnecke, Christina; Kayama, Yosuke; Penov, Kiril; Hennigs, Jan K.; Salomons, Florian; Eken, Suzanne; Emrich, Fabian C.; Zheng, Wei H.; Adam, Matti; Jagger, Ann; Nakagami, Futoshi; Toh, Ryuji; Toyama, Kensuke; Deng, Alicia; Buerke, Michael; Maegdefessel, Lars; Hasenfuß, Gerd; Spin, Joshua M.; Tsao, Philip S.

    2015-01-01

    Rationale Accelerated arterial stiffening is a major complication of diabetes with no specific therapy available up to date. Objective The present study investigates the role of the osteogenic transcription factor Runx2 as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes. Methods and Results Using a murine model of type 2 diabetes (db/db mice) we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae as well as in thoracic aortic samples from type 2 diabetic patients. Vascular smooth muscle-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that Runx2 expression in diabetes is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. Conclusion In conclusion this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes, promoting arterial stiffness irrespective of calcification. PMID:26208651

  18. Minimally Invasive Versus Conventional Aortic Valve Replacement

    PubMed Central

    Attia, Rizwan Q.; Hickey, Graeme L.; Grant, Stuart W.; Bridgewater, Ben; Roxburgh, James C.; Kumar, Pankaj; Ridley, Paul; Bhabra, Moninder; Millner, Russell W. J.; Athanasiou, Thanos; Casula, Roberto; Chukwuemka, Andrew; Pillay, Thasee; Young, Christopher P.

    2016-01-01

    Objective Minimally invasive aortic valve replacement (MIAVR) has been demonstrated as a safe and effective option but remains underused. We aimed to evaluate outcomes of isolated MIAVR compared with conventional aortic valve replacement (CAVR). Methods Data from The National Institute for Cardiovascular Outcomes Research (NICOR) were analyzed at seven volunteer centers (2006–2012). Primary outcomes were in-hospital mortality and midterm survival. Secondary outcomes were postoperative length of stay as well as cumulative bypass and cross-clamp times. Propensity modeling with matched cohort analysis was used. Results Of 307 consecutive MIAVR patients, 151 (49%) were performed during the last 2 years of study with a continued increase in numbers. The 307 MIAVR patients were matched on a 1:1 ratio. In the matched CAVR group, there was no statistically significant difference in in-hospital mortality [MIAVR, 4/307,(1.3%); 95% confidence interval (CI), 0.4%–3.4% vs CAVR, 6/307 (2.0%); 95% CI, 0.8%–4.3%; P = 0.752]. One-year survival rates in the MIAVR and CAVR groups were 94.4% and 94.6%, respectively. There was no statistically significant difference in midterm survival (P = 0.677; hazard ratio, 0.90; 95% CI, 0.56–1.46). Median postoperative length of stay was lower in the MIAVR patients by 1 day (P = 0.009). The mean cumulative bypass time (94.8 vs 91.3 minutes; P = 0.333) and cross-clamp time (74.6 vs 68.4 minutes; P = 0.006) were longer in the MIAVR group; however, this was significant only in the cross-clamp time comparison. Conclusions Minimally invasive aortic valve replacement is a safe alternative to CAVR with respect to operative and 1-year mortality and is associated with a shorter postoperative stay. Further studies are required in high-risk (logistic EuroSCORE > 10) patients to define the role of MIAVR. PMID:26926521

  19. Computational Study of Growth and Remodeling in the Aortic Arch

    PubMed Central

    Alford, Patrick W.; Taber, Larry A.

    2009-01-01

    Opening angles (OAs) are associated with growth and remodeling in arteries. One curiosity has been the relatively large OAs found in the aortic arch of some animals. Here, we use computational models to explore the reasons behind this phenomenon. The artery is assumed to contain a smooth muscle/collagen phase and an elastin phase. In the models, growth and remodeling of smooth muscle/collagen depends on wall stress and fluid shear stress. Remodeling of elastin, which normally turns over very slowly, is neglected. The results indicate that OAs generally increase with longitudinal curvature (torus model), earlier elastin production during development, and decreased wall stiffness. Correlating these results with available experimental data suggests that all of these effects may contribute to the large OAs in the aortic arch. The models also suggest that the slow turnover rate of elastin limits longitudinal growth. These results should promote increased understanding of the causes of residual stress in arteries. PMID:18792831

  20. Intraoperative tracking of aortic valve plane

    PubMed Central

    Nguyen, Duc Long Hung; Garreau, Mireille; Auffret, Vincent; Le Breton, Hervé; Verhoye, Jean-Philippe; Haigron, Pascal

    2013-01-01

    The main objective of this work is to track the aortic valve plane in intra-operative fluoroscopic images in order to optimize and secure Transcatheter Aortic Valve Implantation (TAVI) procedure. This paper is focused on the issue of aortic valve calcifications tracking in fluoroscopic images. We propose a new method based on the Tracking-Learning-Detection approach, applied to the aortic valve calcifications in order to determine the position of the aortic valve plane in intra-operative TAVI images. This main contribution concerns the improvement of object detection by updating the recursive tracker in which all features are tracked jointly. The approach has been evaluated on four patient databases, providing an absolute mean displacement error less than 10 pixels ≈ 2mm). Its suitability for the TAVI procedure has been analyzed. PMID:24110703

  1. Organ protection during aortic cross-clamping.

    PubMed

    Yeung, Kak Khee; Groeneveld, Menno; Lu, Joyce Ja-Ning; van Diemen, Pepijn; Jongkind, Vincent; Wisselink, Willem

    2016-09-01

    Open surgical repair of an aortic aneurysm requires aortic cross-clamping, resulting in temporary ischemia of all organs and tissues supplied by the aorta distal to the clamp. Major complications of open aneurysm repair due to aortic cross-clamping include renal ischemia-reperfusion injury and postoperative colonic ischemia in case of supra- and infrarenal aortic aneurysm repair. Ischemia-reperfusion injury results in excessive production of reactive oxygen species and in oxidative stress, which can lead to multiple organ failure. Several perioperative protective strategies have been suggested to preserve renal function during aortic cross-clamping, such as pharmacotherapy and therapeutic hypothermia of the kidneys. In this chapter, we will briefly discuss the pathophysiology of ischemia-reperfusion injury and the preventative measures that can be taken to avoid abdominal organ injury. Finally, techniques to minimize the risk of complications during and after open aneurysm repair will be presented. PMID:27650341

  2. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    SciTech Connect

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

  3. Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia.

    PubMed

    Smith-Jackson, K; Hentschke, M R; Poli-de-Figueiredo, C E; Pinheiro da Costa, B E; Kurlak, L O; Broughton Pipkin, F; Czajka, A; Mistry, H D

    2015-05-01

    Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation. PMID:25707739

  4. Influence of beta-blocker therapy on aortic blood flow in patients with bicuspid aortic valve.

    PubMed

    Allen, Bradley D; Markl, Michael; Barker, Alex J; van Ooij, Pim; Carr, James C; Malaisrie, S Chris; McCarthy, Patrick; Bonow, Robert O; Kansal, Preeti

    2016-04-01

    In patients with bicuspid aortic valve (BAV), beta-blockers (BB) are assumed to slow ascending aorta (AAo) dilation by reducing wall shear stress (WSS) on the aneurysmal segment. The aim of this study was to assess differences in AAo peak velocity and WSS in BAV patients with and without BB therapy. BAV patients receiving BB (BB+, n = 30, age: 47 ± 11 years) or not on BB (BB-, n = 30, age: 46 ± 13 years) and healthy controls (n = 15, age: 43 ± 11 years) underwent 4D flow MRI for the assessment of in vivo aortic 3D blood flow. Peak systolic velocities and 3D WSS were calculated at the anterior and posterior walls of the AAo. Both patient groups had higher maximum and mean WSS relative to the control group (p = 0.001 to p = 0.04). WSS was not reduced in the BB+ group compared to BB- patients in the anterior AAo (maximum: 1.49 ± 0.47 vs. 1.38 ± 0.49 N/m(2), p = 0.99, mean: 0.76 ± 0.2 vs. 0.74 ± 0.18 N/m(2), p = 1.00) or posterior AAo (maximum: 1.45 ± 0.42 vs. 1.39 ± 0.58 N/m(2), p = 1.00; mean: 0.65 ± 0.16 vs. 0.63 ± 0.16 N/m(2), p = 1.00). AAo peak velocity was elevated in patients compared to controls (p < 0.01) but similar for BB+ and BB- groups (p = 0.42). Linear models identified significant relationships between aortic stenosis severity and increased maximum WSS (β = 0.186, p = 0.007) and between diameter at the sinus of Valsalva and reduced mean WSS (β = -0.151, p = 0.045). Peak velocity and systolic WSS were similar for BAV patients irrespective of BB therapy. Further prospective studies are needed to investigate the impact of dosage and duration of BB therapy on aortic hemodynamics and development of aortopathy. PMID:26817758

  5. Successful management of para-aortic lymphocyst with laparoscopic fenestration.

    PubMed

    Sarli, L; Cortellini, P; Pavlidis, C; Simonazzi, M; Sebastio, N

    2000-04-01

    Para-aortic lymphocyst occasionally follows retroperitoneal para-aortic node dissection for neoplastic diseases. We present a case in which the leakage of chylous fluid and then a para-aortic lymphocyst followed right nephrectomy and para-aortic node dissection for kidney cancer. Our method of treatment utilized conservative management of chylous ascites and laparoscopic internal drainage of the retroperitoneal lymphocyst.

  6. 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.

  7. Molecular beacons can assess changes in expression and 3'-polyadenylation of human eNOS mRNA.

    PubMed

    Jones, Rachel; Baker, Meredith B; Weber, Martina; Harrison, David G; Bao, Gang; Searles, Charles D

    2009-03-01

    The endothelium plays an essential role in maintaining vascular homeostasis, and it fulfills this role by modulating intracellular signaling and gene expression in response to chemical and mechanical stimuli. Assessing changes in endothelial gene expression is essential to understanding how physiological and pathophysiological processes modulate vascular homeostasis. Here we describe the use of molecular beacons to rapidly and quantitatively assess expression and 3'-polyadenylation of a gene that is important for vascular homeostasis, endothelial nitric oxide synthase (eNOS). Single- and dual-fluorescence resonance energy transfer (FRET) molecular beacon hybridization assays were developed to measure changes in mRNA levels and 3'-polyadenylation, respectively, in primary human endothelial cell cultures subjected to laminar shear stress or statin treatment. Optimized beacon hybridization assays took approximately 15 min to perform, and eNOS mRNA levels were validated by quantitative real-time RT-PCR. Competitive inhibition assays and posttranscriptional silencing of eNOS expression were used to verify the specificity of molecular beacon fluorescence. Finally, the dual-FRET method was used to assess eNOS polyadenylation in tissues isolated from mice subjected to exercise training. These data demonstrate that molecular beacons can be used to rapidly and efficiently measure endothelial gene expression and 3'-polyadenylation. This approach could easily be adapted for studies of other endothelial genes and has promise for applications in live endothelial cells.

  8. Endovascular abdominal aortic aneurysm repair

    PubMed Central

    Norwood, M G A; Lloyd, G M; Bown, M J; Fishwick, G; London, N J; Sayers, R D

    2007-01-01

    The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique. PMID:17267674

  9. Leaking mycotic abdominal aortic aneurysm.

    PubMed

    Sing, T M; Young, N; O'Rourke, I C; Tomlinson, P

    1994-11-01

    A case of leaking mycotic abdominal aortic aneurysm is reported, with a brief review of the literature. A 58 year old female presented with shoulder and abdominal pain associated with diarrhoea, vomiting and fever with leucocytosis. Computed tomography of the abdomen showed pooling of contrast in the retroperitoneum anterior to a non-dilated abdominal aorta. There was considerable retroperitoneal blood accumulating in a mass-like lesion in the right lower abdomen and pelvis obstructing the right renal collecting system. Laparotomy revealed a 4 cm diameter saccular aneurysm of the abdominal aorta, with a 1 cm diameter neck. Culture of the thrombus grew Streptococcus pyogenes. PMID:7993259

  10. Aortic valve and ascending aortic root modeling from 3D and 3D+t CT

    NASA Astrophysics Data System (ADS)

    Grbic, Saša; Ionasec, Razvan I.; Zäuner, Dominik; Zheng, Yefeng; Georgescu, Bogdan; Comaniciu, Dorin

    2010-02-01

    Aortic valve disorders are the most frequent form of valvular heart disorders (VHD) affecting nearly 3% of the global population. A large fraction among them are aortic root diseases, such as aortic root aneurysm, often requiring surgical procedures (valve-sparing) as a treatment. Visual non-invasive assessment techniques could assist during pre-selection of adequate patients, planning procedures and afterward evaluation of the same. However state of the art approaches try to model a rather short part of the aortic root, insufficient to assist the physician during intervention planning. In this paper we propose a novel approach for morphological and functional quantification of both the aortic valve and the ascending aortic root. A novel physiological shape model is introduced, consisting of the aortic valve root, leaflets and the ascending aortic root. The model parameters are hierarchically estimated using robust and fast learning-based methods. Experiments performed on 63 CT sequences (630 Volumes) and 20 single phase CT volumes demonstrated an accuracy of 1.45mm and an performance of 30 seconds (3D+t) for this approach. To the best of our knowledge this is the first time a complete model of the aortic valve (including leaflets) and the ascending aortic root, estimated from CT, has been proposed.

  11. Aortic root size and prevalence of aortic regurgitation in elite strength trained athletes.

    PubMed

    Babaee Bigi, Mohammad Ali; Aslani, Amir

    2007-08-01

    Athletes involved in mainly static or isometric exercise (e.g., weight lifting, power lifting, and bodybuilding) develop pressure overloads due to the high systemic arterial pressure found in this type of exercise. It is hypothesized that chronically elevated aortic wall tension in strength-trained athletes is associated with aortic dilatation and regurgitation. The aim of this study was to evaluate aortic root size and the prevalence of aortic regurgitation in elite strength-trained athletes. The cohort included 100 male athletes (mean age 22.1 +/- 3.6 years; all were finalists or medalists in the country) and 128 healthy age- and height-matched subjects (the control group). Aortic root diameters at end-diastole were measured at 4 locations: (1) the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction, and (4) the maximal diameter of the proximal ascending aorta. Aortic root diameters at all levels were significantly greater in the strength-trained athletes (p <0.05 for all comparisons). When the strength-trained athletes were divided into quartiles of duration of high-intensity strength training (first quartile: <18 months; second quartile: >18 and <36 months; third quartile: >36 and <54 months; fourth quartile: >54 months), progressive enlargement was found at all aortic diameters. In conclusion, aortic root diameters in all segments of the aortic root were significantly greater in elite strength-trained athletes compared with an age- and height-matched population.

  12. Nontraumatic avulsion of aortic valve commissure as a cause of acute aortic valve regurgitation

    PubMed Central

    Chang, Rei-Yeuh; Chen, Chien-Chang; Hsu, Wei-Pang; Hsiao, Pei-Ching; Tsai, Han-Lin; Hsiao, Ping-Gune; Wu, Jiann-Der; Guo, How-Ran

    2016-01-01

    Abstract Background: Avulsion of the aortic valve commissure as a cause of acute aortic valve regurgitation is mostly due to trauma, infective endocarditis, or ascending aortic dissection. Nontraumatic avulsion of the aortic valve commissure is very rare. We reviewed the literature and analyzed potential risk factors of nontraumatic avulsion. Case presentation: An 80-year-old male with hypertension was seen in the emergency department with acute onset dyspnea. Echocardiogram revealed left ventricular hypertrophy with adequate systolic function, prolapse of the noncoronary cusp, and incomplete coaptation of the right coronary and noncoronary cusps with severe aortic valve regurgitation. Surgery revealed an avulsion between the left coronary and noncoronary cusps. Histopathology examination of the aortic valve showed myxoid degeneration, fibrosis, and calcification. Examination of the ascending aorta revealed myxoid degeneration and fragmentation of elastic fibers. Aortic valve replacement was performed, and the patient was alive and well 4 years after surgery. A review of the literature showed that more than three-fourths of the similar cases occurred in males, and about half in patients with hypertension and those 60 years of age or older. Conclusions: In the case of acute aortic regurgitation without a history of trauma, infection, or valvotomy, when 2 prolapsed aortic cusps are observed by echocardiography in the absence of an intimal tear of the ascending aorta, an avulsion of the aortic commissure should be suspected, especially in males with hypertension who are 60 years of age or older. PMID:27749570

  13. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity

    SciTech Connect

    Weber, Martina; Baker, Meredith B.; Moore, Jeffrey P.; Searles, Charles D.

    2010-03-19

    Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24 h, 15 dynes/cm{sup 2}) identified 13 miRNAs whose expression was significantly upregulated (p < 0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p = 0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO{sup {center_dot}}) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO{sup {center_dot}} pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.

  14. Giant Thoracic Aneurysm Following Valve Replacement for Bicuspid Aortic Valve.

    PubMed

    Tran, Cao; Ul Haq, Ehtesham; Nguyen, Ngoc; Omar, Bassam

    2015-01-01

    Bicuspid aortic valve is a common congenital anomaly associated with aortopathy, which can cause aortic root dilatation, necessitating regular screening if the aortic root is > 4.0 cm. Despite the low absolute incidence of aortic complications associated with bicuspid aortic valve in the general population, the consequences of such complications for an individual patient can be devastating. Herein we propose a balanced algorithm that incorporates recommendations from the three major guidelines for follow-up imaging of the aortic root and ascending thoracic aorta in patients with a bicuspid aortic valve, maintaining the current recommendations with regard to surgical thresholds. PMID:26827748

  15. Left ventricular function in chronic aortic regurgitation

    SciTech Connect

    Iskandrian, A.S.; Hakki, A.H.; Manno, B.; Amenta, A.; Kane, S.A.

    1983-06-01

    Left ventricular performance was determined in 42 patients with moderate or severe aortic regurgitation during upright exercise by measuring left ventricular ejection fraction and volume with radionuclide ventriculography. Classification of the patients according to exercise tolerance showed that patients with normal exercise tolerance (greater than or equal to 7.0 minutes) had a significantly higher ejection fraction at rest (probability (p) . 0.02) and during exercise (p . 0.0002), higher cardiac index at exercise (p . 0.0008) and lower exercise end-systolic volume (p . 0.01) than did patients with limited exercise tolerance. Similar significant differences were noted in younger patients compared with older patients in ejection fraction at rest and exercise (both p . 0.001) and cardiac index at rest (p . 0.03) and exercise (p . 0.0005). The end-diastolic volume decreased during exercise in 60% of the patients. The patients with a decrease in volume were significantly younger and had better exercise tolerance and a larger end-diastolic volume at rest than did patients who showed an increase in volume. The mean corrected left ventricular end-diastolic radius/wall thickness ratio was significantly greater in patients with abnormal than in those with normal exercise reserve (mean +/- standard deviation 476 +/- 146 versus 377 +/- 92 mm Hg, p less than 0.05). Thus, in patients with chronic aortic regurgitation: 1) left ventricular systolic function during exercise was related to age, exercise tolerance and corrected left ventricular end-diastolic radius/wall thickness ratio, and 2) the end-diastolic volume decreased during exercise, especially in younger patients and patients with normal exercise tolerance or a large volume at rest.

  16. Current Clinical Evidence on Rapid Deployment Aortic Valve Replacement

    PubMed Central

    Barnhart, Glenn R.; Shrestha, Malakh Lal

    2016-01-01

    Abstract Aortic stenosis is the most common valvular heart disease in the Western world. It is caused p