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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. PGC-1α ameliorates AngiotensinII-induced eNOS dysfunction in human aortic endothelial cells.

    PubMed

    Li, Jie; Geng, Xiao-Yong; Cong, Xiao-Liang

    2016-08-01

    Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we investigated the effects of PGC-1α on eNOS dysfunction and further explore the underlying mechanisms. The results showed that PGC-1α expression was downregulated after AngiotensinII (AngII) treatment and paralleled with the decreased NO generation in human aortic endothelial cells. Overexpression of PGC-1α with adenovirus or pharmacological agonist ameliorated AngII-induced the decrease of NO generation, evidenced by the restoration of cGMP and nitrite concentration. Rather than affecting eNOS expression and uncoupling, PGC-1α inhibited AngII-induced decrease of eNOS serine 1177 phosphorylation through activation of PI3K/Akt signaling. In addition, PGC-1α overexpression suppressed AngII-induced the increase of PP2A-A/eNOS interaction and PP2A phosphatase activity, with a concomitant decrease in PP2A phosphorylation, leading to eNOS serine 1177 phosphorylation. However, pharmacological inhibition of PI3K/Akt signaling blunted the observed effect of PGC-1α on PP2A activity. Taken together, our findings suggest that PGC-1α overexpression improves AngII-induced eNOS dysfunction and that improved eNOS dysfunction is associated with activated PI3K/Akt pathway, impaired PP2A activity and reduced PP2A-A/eNOS association. These date indicate that forced PGC-1α expression may be a novel therapeutic approach for endothelial dysfunction. PMID:27235860

  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. ICAM-1-activated Src and eNOS signaling increase endothelial cell surface PECAM-1 adhesivity and neutrophil transmigration.

    PubMed

    Liu, Guoquan; Place, Aaron T; Chen, Zhenlong; Brovkovych, Viktor M; Vogel, Stephen M; Muller, William A; Skidgel, Randal A; Malik, Asrar B; Minshall, Richard D

    2012-08-30

    Polymorphonuclear neutrophil (PMN) extravasation requires selectin-mediated tethering, intercellular adhesion molecule-1 (ICAM-1)-dependent firm adhesion, and platelet/endothelial cell adhesion molecule 1 (PECAM-1)-mediated transendothelial migration. An important unanswered question is whether ICAM-1-activated signaling contributes to PMN transmigration mediated by PECAM-1. We tested this concept and the roles of endothelial nitric oxide synthase (eNOS) and Src activated by PMN ligation of ICAM-1 in mediating PECAM-1-dependent PMN transmigration. We observed that lung PMN infiltration in vivo induced in carrageenan-injected WT mice was significantly reduced in ICAM-1(-/-) and eNOS(-/-) mice. Crosslinking WT mouse ICAM-1 expressed in human endothelial cells (ECs), but not the phospho-defective Tyr(518)Phe ICAM-1 mutant, induced SHP-2-dependent Src Tyr530 dephosphorylation that resulted in Src activation. ICAM-1 activation also stimulated phosphorylation of Akt (p-Ser473) and eNOS (p-Ser1177), thereby increasing NO production. PMN migration across EC monolayers was abolished in cells expressing the Tyr(518)Phe ICAM-1 mutant or by pretreatment with either the Src inhibitor PP2 or eNOS inhibitor L-NAME. Importantly, phospho-ICAM-1 induction of Src signaling induced PECAM-1 Tyr686 phosphorylation and increased EC surface anti-PECAM-1 mAb-binding activity. These results collectively show that ICAM-1-activated Src and eNOS signaling sequentially induce PECAM-1-mediated PMN transendothelial migration. Both Src and eNOS inhibition may be important therapeutic targets to prevent or limit vascular inflammation. PMID:22806890

  8. 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

  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.

  10. Sympathetic activation increases NO release from eNOS but neither eNOS nor nNOS play an essential role in exercise hyperemia in the human forearm

    PubMed Central

    Shabeeh, Husain; Seddon, Michael; Brett, Sally; Melikian, Narbeh; Casadei, Barbara; Shah, Ajay M.

    2013-01-01

    Nitric oxide (NO) release from endothelial NO synthase (eNOS) and/or neuronal NO synthase (nNOS) could be modulated by sympathetic nerve activity and contribute to increased blood flow after exercise. We examined the effects of brachial-arterial infusion of the nNOS selective inhibitor S-methyl-l-thiocitrulline (SMTC) and the nonselective NOS inhibitor NG-monomethyl-l-arginine (l-NMMA) on forearm arm blood flow at rest, during sympathetic activation by lower body negative pressure, and during lower body negative pressure immediately after handgrip exercise. Reduction in forearm blood flow by lower body negative pressure during infusion of SMTC was not significantly different from that during vehicle (−28.5 ± 4.02 vs. −34.1 ± 2.96%, respectively; P = 0.32; n = 8). However, l-NMMA augmented the reduction in forearm blood flow by lower body negative pressure (−44.2 ± 3.53 vs. −23.4 ± 5.71%; n = 8; P < 0.01). When lower body negative pressure was continued after handgrip exercise, there was no significant effect of either l-NMMA or SMTC on forearm blood flow immediately after low-intensity exercise (P = 0.91 and P = 0.44 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10) or high-intensity exercise (P = 0.46 and P = 0.68 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10). These results suggest that sympathetic activation increases NO release from eNOS, attenuating vasoconstriction. Dysfunction of eNOS could augment vasoconstrictor and blood pressure responses to sympathetic activation. However, neither eNOS nor nNOS plays an essential role in postexercise hyperaemia, even in the presence of increased sympathetic activation. PMID:23436331

  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. Xuezhikang, Extract of Red Yeast Rice, Improved Abnormal Hemorheology, Suppressed Caveolin-1 and Increased eNOS Expression in Atherosclerotic Rats

    PubMed Central

    Yang, Ya-Bing; Liu, Mei-Lin

    2013-01-01

    Background Xuezhikang is the extract of red yeast rice, which has been widely used for the management of atherosclerotic disease, but the molecular basis of its antiatherosclerotic effects has not yet been fully identified. Here we investigated the changes of eNOS in vascular endothelia and RBCs, eNOS regulatory factor Caveolin-1 in endothelia, and hemorheological parameters in atherosclerotic rats to explore the protective effects of Xuezhikang. Methodology/Principal Findings Wistar rats were divided into 4 groups (n = 12/group) group C, controls; group M, high-cholesterol diet (HCD) induced atherosclerotic models; group X, HCD+Xuezhikang; and group L, HCD +Lovastatin. In group X, Xuezhikang inhibited oxidative stress, down-regulated caveolin-1 in aorta wall (P<0.05), up-regulated eNOS expression in vascular endothelia and erythrocytes (P<0.05), increased NOx (nitrite and nitrate) in plasma and cGMP in erythrocyte plasma and aorta wall (P<0.05), increased erythrocyte deformation index (EDI), and decreased whole blood viscosity and plasma viscosity (P<0.05), with the improvement of arterial pathology. Conclusions/Significance Xuezhikang up-regulated eNOS expression in vascular endothelia and RBCs, increased plasma NOx and improved abnormal hemorheology in high cholesterol diet induced atherosclerotic rats. The elevated eNOS/NO and improved hemorheology may be beneficial to atherosclerotic disease. PMID:23675421

  14. Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing eNOS in Healthy Normolipidemic Older Adults

    PubMed Central

    Walker, Ashley E; Kaplon, Rachelle E; Lucking, Sara Marian S; Russell-Nowlan, Molly J; Eckel, Robert H; Seals, Douglas R

    2013-01-01

    Vascular endothelial dysfunction develops with aging, as indicated by impaired endothelium-dependent dilation(EDD), and is related to increased cardiovascular disease risk. We hypothesized that short-term treatment with fenofibrate, a lipid-lowering agent with potential pleiotropic effects, would improve EDD in middle-aged and older normolipidemic adults by reducing oxidative stress. Brachial artery flow-mediated dilation (FMD), a measure of EDD, was assessed in 22healthy adults aged 50-77 years before and after 7days of fenofibrate (145 mg/d; n=12/7M) or placebo (n=10/5M). Brachial FMD was unchanged with placebo, but improved after 2 and 7 days of fenofibrate (5.1±0.7 vs. 2d: 6.0±0.7 and 7d: 6.4±0.6 %Δ; both P<0.005). The improvements in FMD after 7 days remained significant (P<0.05) after accounting for modest changes in plasma total and LDL-cholesterol. Endothelium-independent dilation was not affected by fenofibrate or placebo (P>0.05). Infusion (i.v.) of the antioxidant vitamin C improved brachial FMD at baseline in both groups and during placebo treatment (P<0.05), but not after 2 and 7 days of fenofibrate (P>0.05). Fenofibrate treatment also reduced plasma oxidized LDL, a systemic marker of oxidative stress, compared with placebo (P<0.05). In vascular endothelial cells sampled from peripheral veins of the subjects, endothelial nitric oxide synthase (eNOS) protein expression was unchanged with placebo and after 2 days of fenofibrate, but was increased after 7 days of fenofibrate (0.54±0.03 vs. 2d: 0.52±0.04 and 7d: 0.76±0.11 intensity/HUVEC control; P<0.05 7d). Short-term treatment with fenofibrate improves vascular endothelial function in healthy normolipidemic middle-aged/older adults by reducing oxidative stress and induces increases in eNOS. PMID:23108655

  15. 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

  16. Screening for abdominal aortic aneurysms does not increase psychological morbidity.

    PubMed Central

    Khaira, H. S.; Herbert, L. M.; Crowson, M. C.

    1998-01-01

    Screening can lead to harmful psychological effects in the screened population--an argument used against abdominal aortic aneurysm (AAA) screening. However, there is no evidence for this in AAA screening. We applied the Hospital Anxiety and Depression Scale (HADS) to a group of men undergoing screening for AAA. The HADS questionnaire was completed by subjects found not to have AAA, subjects with known small aneurysms attending for follow-up scans, subjects with known AAA on waiting lists for surgery, and controls not involved in the screening programme. The groups were well matched for age and the number of additional diseases. There was no significant difference in the distribution of patients for anxiety and depression according to the HADS questionnaire (chi 2 test, P > 0.1). The results from this study suggest that AAA screening does not increase anxiety or depression in the screened subjects--contrary to the argument put forward against screening for this condition. PMID:9849335

  17. Aortic input impedance increases with age in healthy men and women.

    PubMed

    Mazzaro, Luciano; Almasi, Stephen J; Shandas, Robin; Seals, Douglas R; Gates, Phillip E

    2005-06-01

    Aortic input impedance represents the hydraulic load presented by the systemic circulation to the left ventricle of the heart and is increased in patients with cardiovascular disease. Aging is a strong independent risk factor for cardiovascular disease and could exert this effect partly through an increase in modulus of aortic input impedance. We used a novel noninvasive technique to determine aortic input impedance in 71 healthy men and women aged 20 to 69 years. We found that the aortic input impedance spectrum was shifted rightward with advancing age, characterized by a 37% increase in the frequency of the minimum modulus between the third and seventh decade (P<0.0001). The frequency of the minimum modulus correlated with age in all subjects (r=0.48; P<0.0001), in men (r=0.43; P<0.005), and in women (r=0.53; P=0.001). Although several physical characteristics were associated with the frequency of the minimum modulus (bivariate correlation), a regression model that included age and these physical characteristics showed that age was the only independent predictor of the frequency of the minimum modulus. We conclude that aortic input impedance increases with advancing age in healthy men and women. This increase in aortic input impedance may be an important mechanism by which age increases the risk of cardiovascular disease in humans. PMID:15867143

  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. The mild form of mucopolysaccharidosis type I (Scheie syndrome) is associated with increased ascending aortic stiffness.

    PubMed

    Nemes, Attila; Timmermans, Remco G M; Wilson, J H Paul; Soliman, Osama I I; Krenning, Boudewijn J; ten Cate, Folkert J; Geleijnse, Marcel L

    2008-03-01

    Mucopolysaccharidosis type I (MPS IS) is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase, which is involved in the degradation of sulfated glycosaminoglycans (GAGs). The deficiency results in the intra-and pericellular accumulation of the GAGs heparan sulfate and dermatan sulfate. Eight adult patients with typical features of MPS IS aged 31.5 +/- 6.8 years (five men) were included and compared to age-and gender-matched controls. With transthoracic echocardiography, cyclic ascending aortic diameter changes were measured and ascending aortic elastic properties were calculated to characterize aortic elasticity. In MPS IS patients, aortic stiffness index was significantly increased (23.1 +/- 10.4 vs 3.9 +/- 1.5, P < 0.001), while aortic distensibility was significantly decreased (1.6 +/- 0.8 vs 4.6 [corrected] +/- 1.9 cm(2)/dynes [corrected] 10(-6), P < 0.001) compared to age-and sex-matched controls. The results of the present study demonstrate that in addition to the known cardiac complications, MPS IS patients have an impairment of ascending aortic elasticity. Further follow-up studies are needed to examine arterial elasticity using other methods in this patient population, and to detect possible effects of enzyme replacement therapy. PMID:18389335

  20. Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1

    PubMed Central

    Beckner, Marie E.; Pollack, Ian F.; Nordberg, Mary L.; Hamilton, Ronald L.

    2015-01-01

    Background Prominence of glycolysis in glioblastomas may be non-specific or a feature of oncogene-related subgroups (i.e. amplified EGFR, etc.). Relationships between amplified oncogenes and expressions of metabolic genes associated with glycolysis, directly or indirectly via pH, were therefore investigated. Methods Using multiplex ligation-dependent probe amplification, copy numbers (CN) of 78 oncogenes were quantified in 24 glioblastomas. Related expressions of metabolic genes encoding lactate dehydrogenases (LDHA, LDHC), carbonic anhydrases (CA3, CA12), monocarboxylate transporters (SLC16A3 or MCT4, SLC16A4 or MCT5), ATP citrate lyase (ACLY), glycogen synthase1 (GYS1), hypoxia inducible factor-1A (HIF1A), and enolase1 (ENO1) were determined in 22 by RT-qPCR. To obtain supra-glycolytic levels and adjust for heterogeneity, concurrent ENO1 expression was used to mathematically transform the expression levels of metabolic genes already normalized with delta-delta crossing threshold methodology. Results Positive correlations with EGFR occurred for all metabolic genes. Significant differences (Wilcoxon Rank Sum) for oncogene CN gains in tumors of at least 2.00-fold versus less than 2.00-fold occurred for EGFR with CA3's expression (p < 0.03) and for RNF139 with CA12 (p < 0.004). Increased CN of XIAP associated negatively. Tumors with less than 2.00-fold CN gains differed from those with gains for XIAP with CA12 (p < 0.05). Male gender associated with CA12 (p < 0.05). Conclusions Glioblastomas with CN increases in EGFR had elevated CA3 expression. Similarly, tumors with RNF149 CN gains had elevated CA12 expression. General significance In larger studies, subgroups of glioblastomas may emerge according to oncogene-related effects on glycolysis, such as control of pH via effects on carbonic anhydrases, with prognostic and treatment implications. PMID:27051584

  1. Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis.

    PubMed

    Blyme, Adam; Asferg, Camilla; Nielsen, Olav W; Boman, Kurt; Gohlke-Bärwolf, Christa; Wachtell, Kristian; Olsen, Michael H

    2016-06-01

    Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p < 0.001). In Cox-regression analyses, hsCRP1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc = 47.3% versus AVRhighCRP0CRP1dec = 27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP0 eliminating the difference in incidence of AVR between high versus low hsCRP0 (AVRhighCRP0CRP1dec = 27.5% versus AVRlowCRP0CRP1dec = 25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed. PMID:26911132

  2. Programmed Speed Reduction Enables Aortic Valve Opening and Increased Pulsatility in the LVAD-Assisted Heart.

    PubMed

    Tolpen, Sam; Janmaat, Jochem; Reider, Claudine; Kallel, Faouzi; Farrar, David; May-Newman, Karen

    2015-01-01

    Aortic valve opening (AVO) during left ventricular assist device (LVAD) support aids in preventing valve fusion, incompetence, and thrombosis. The programmed low speed algorithm (PLSA) allows AVO intermittently by reducing continuous motor speed during a dwell time. AVO and hemodynamics in the LVAD-assisted heart were measured using a HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD with a PLSA controller in a mock circulatory loop. Left ventricle and aortic pressures, LVAD, and total aortic flow were measured during pre-LVAD, non-PLSA and PLSA combinations of cardiac function, and LVAD speed. The low cardiac setting corresponded to a pre-LVAD cardiac output of 2.8 L/min, stroke volume of 40 ml, and ejection fraction of 22%; the medium setting produced values of 3.5 L/min, 50 ml, and 28%, respectively. Results show that the PLSA controller set at 10 krpm, dropping to 7 krpm for dwell time of 6 s, adequately produced AVO for all tested cardiac functions with only minimal changes in cardiac output. However, AVO frequency was independent of opening area and systolic duration, which both decreased with increasing LVAD support. Furthermore, aortic pulsatility index quadrupled in the aortic root and doubled in the distal aorta during PLSA conditions, providing evidence that AVO and blood mixing are enabled by PLSA control at the appropriate speed. PMID:25961849

  3. Increased aortic stiffness and blood pressure in non-classic Pompe disease.

    PubMed

    Wens, Stephan C A; Kuperus, Esther; Mattace-Raso, Francesco U S; Kruijshaar, Michelle E; Brusse, Esther; van Montfort, Kees C A G M; de Boer, Marjan Scheltens-; Sijbrands, Eric J G; van der Ploeg, Ans T; van Doorn, Pieter A

    2014-05-01

    Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20%), more Pompe patients had a history of hypertension (36%, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly. PMID:24407465

  4. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.

    PubMed

    Battault, Sylvain; Singh, François; Gayrard, Sandrine; Zoll, Joffrey; Reboul, Cyril; Meyer, Grégory

    2016-02-01

    Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation. PMID:26537830

  5. 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

  6. 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

  7. Vascular Smooth Muscle Cell Stiffness as a Mechanism for Increased Aortic Stiffness with Aging

    PubMed Central

    Qiu, Hongyu; Zhu, Yi; Sun, Zhe; Trzeciakowski, Jerome P.; Gansner, Meredith; Depre, Christophe; Resuello, Ranillo R.G.; Natividad, Filipinas F.; Hunter, William C.; Genin, Guy M.; Elson, Elliot L.; Vatner, Dorothy E.; Meininger, Gerald A.; Vatner, Stephen F.

    2010-01-01

    Rationale Increased aortic stiffness, an important feature of many vascular diseases, e.g., aging, hypertension, atherosclerosis and aortic aneurysms, is assumed due to changes in extracellular matrix (ECM). Objective We tested the hypothesis that the mechanisms also involve intrinsic stiffening of vascular smooth muscle cells (VSMCs). Methods and Results Stiffness was measured in vitro both by atomic force microscopy (AFM) and in a reconstituted tissue model, using VSMCs from aorta of young versus old male monkeys (Macaca fascicularis, n=7/group), where aortic stiffness increases by 200 % in vivo. The apparent elastic modulus was increased (P<0.05) in old VSMCs (41.7±0.5 kPa) versus young (12.8±0.3 kPa), but not after disassembly of the actin cytoskeleton with cytochalasin D. Stiffness of the VSMCs in the reconstituted tissue model was also higher (P<0.05) in old (23.3±3.0 kPa) than in young (13.7±2.4 kPa). Conclusions These data support the novel concept, not appreciated previously, that increased vascular stiffness with aging is due not only to changes in ECM, but also to intrinsic changes in VSMCs. PMID:20634486

  8. 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

  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. 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

  12. 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

  13. 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. PMID:25814070

  14. Abnormal regional myocardial deformation properties and increased aortic stiffness in normotensive patients with aortic coarctation despite successful correction: an ABPM, standard echocardiography and strain rate imaging study.

    PubMed

    di Salvo, Giovanni; Pacileo, Giuseppe; Limongelli, Giuseppe; Verrengia, Marina; Rea, Alessandra; Santoro, Giuseppe; Gala, Simona; Castaldi, Biagio; D'Andrea, Antonello; Caso, Pio; Giovanna Russo, Maria; Calabró, Raffaele

    2007-09-01

    The long-term follow-up data subsequent to a successful repair of AoC (aortic coarctation) show that life expectancy remains reduced. Previous standard echocardiographic studies have demonstrated normal or increased systolic cardiac function in patients following successful repair of AoC. SR (strain rate) imaging is a new technique able to detect subclinical myocardial abnormalities. In the present study we investigated whether young patients (without hypertension, as assessed using ambulatory blood pressure monitoring and an exercise test) following successful AoC repair already have abnormal myocardial deformation properties, and the relationship of the deformation properties with aortic stiffness. We studied 166 subjects, 83 AoC non-hypertensive patients (mean age 12+/-4 years) a number of years after successful repair of AoC and 83 age- and sex-matched subjects as controls. Peak systolic SR (1/s) for both regional longitudinal and radial function was assessed. The aortic stiffness index was calculated from the echocardiographically derived thoracic aortic diameters, and the measurement of blood pressure was obtained by cuff sphygmomanometry. The LV (left ventricular) ejection fraction was significantly increased in AoC patients, whereas regional longitudinal SRs were significantly reduced (-1.1+/-0.9 compared with -2+/-0.5, P<0.0001) in patients. The aortic stiffness index was significantly increased in AoC patients (12+/-9, P<0.0001). At multilinear regression analysis, age at repair (P=0.005; coefficient, -0.201; S.E.M., 0.027) and the aortic stiffness index (P=0.0029; coefficient, 0.334; S.E.M., 0.423) predicted longitudinal SR. Despite the presence of a successful repair for AoC, in the absence of hypertension, longitudinal deformation properties were significantly impaired. Moreover, the degree of longitudinal SR impairment was correlated with age at repair and aortic stiffness. Early repair can delay the onset of hypertension in postcoarctectomy patients

  15. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.

    PubMed

    Yu, Jing; Eto, Masato; Akishita, Masahiro; Kaneko, Akiyo; Ouchi, Yasuyoshi; Okabe, Tetsuro

    2007-02-16

    Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells. PMID:17196933

  16. 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. PMID:22087741

  17. Aortic angiography

    MedlinePlus

    ... with the aorta or its branches, including: Aortic aneurysm Aortic dissection Congenital (present from birth) problems AV ... Abnormal results may be due to: Abdominal aortic aneurysm Aortic dissection Aortic regurgitation Aortic stenosis Congenital (present ...

  18. 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

  19. 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

  20. 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

  1. Obligatory Role for Endothelial Heparan Sulphate Proteoglycans and Caveolae Internalization in Catestatin-Dependent eNOS Activation

    PubMed Central

    Fornero, Sara; Bassino, Eleonora; Ramella, Roberta; Mahata, Sushil K.; Tota, Bruno; Alloatti, Giuseppe

    2014-01-01

    The chromogranin-A peptide catestatin modulates a wide range of processes, such as cardiovascular functions, innate immunity, inflammation, and metabolism. We recently found that the cardiac antiadrenergic action of catestatin requires a PI3K-dependent NO release from endothelial cells, although the receptor involved is yet to be identified. In the present work, based on the cationic properties of catestatin, we tested the hypothesis of its interaction with membrane heparan sulphate proteoglycans, resulting in the activation of a caveolae-dependent endocytosis. Experiments were performed on bovine aortic endothelial cells. Endocytotic vesicles trafficking was quantified by confocal microscopy using a water-soluble membrane dye; catestatin colocalization with heparan sulphate proteoglycans and caveolin 1 internalization were studied by fluorimetric measurements in live cells. Modulation of the catestatin-dependent eNOS activation was assessed by immunofluorescence and immunoblot analysis. Our results demonstrate that catestatin (5 nM) colocalizes with heparan sulphate proteoglycans and induces a remarkable increase in the caveolae-dependent endocytosis and caveolin 1 internalization, which were significantly reduced by both heparinase and wortmannin. Moreover, catestatin was unable to induce Ser1179 eNOS phosphorylation after pretreatments with heparinase and methyl-β-cyclodextrin. Taken together, these results highlight the obligatory role for proteoglycans and caveolae internalization in the catestatin-dependent eNOS activation in endothelial cells. PMID:25136621

  2. Increased systolic load causes adverse remodeling of fetal aortic and mitral valves.

    PubMed

    Tibayan, Frederick A; Louey, Samantha; Jonker, Sonnet; Espinoza, Herbert; Chattergoon, Natasha; You, Fanglei; Thornburg, Kent L; Giraud, George

    2015-12-15

    While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability. PMID:26354842

  3. TNFα reduces eNOS activity in endothelial cells through serine 116 phosphorylation and Pin1 binding: Confirmation of a direct, inhibitory interaction of Pin1 with eNOS.

    PubMed

    Kennard, Simone; Ruan, Ling; Buffett, Ryan J; Fulton, David; Venema, Richard C

    2016-06-01

    Production of NO by the endothelial nitric oxide synthase (eNOS) has a major role in blood pressure control and suppression of atherosclerosis. In a previous study, we presented evidence implicating the Pin1 prolyl isomerase in negative modulation of eNOS activity in bovine aortic endothelial cells (BAECs). Pin1 recognizes phosphoserine/phosphothreonine-proline motifs in target proteins and catalyzes prolyl isomerization at the peptide bond. In the present study, we show, first, with purified proteins, that Pin1 binds to eNOS directly via the Pin1 WW domain. Binding is enhanced by mimicking phosphorylation of eNOS at S116. Interaction of Pin1 with eNOS markedly reduces eNOS enzymatic activity. Second, in BAECs, we show that TNFα induces ERK 1/2-mediated S116 phosphorylation of eNOS, accompanied by Pin1 binding. TNFα treatment of BAECs results in a reduction in NO release from the cells in a manner that depends on the activities of both Pin1 and ERK 1/2. Evidence is also presented that this mechanism of eNOS regulation cannot occur in rat and mouse cells because there is no proline residue in the mouse and rat amino acid sequences adjacent to the putative phosphorylation site. Moreover, we find that phosphorylation of this site is not detectable in mouse eNOS. PMID:27073025

  4. 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. PMID:26351578

  5. 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

  6. Soluble receptor for advanced glycation end products and increased aortic stiffness in the general population.

    PubMed

    Mayer, Otto; Seidlerová, Jitka; Filipovský, Jan; Vágovičová, Petra; Wohlfahrt, Peter; Cífková, Renata; Windrichová, Jindra; Topolčan, Ondřej

    2016-04-01

    It has been suggested that accumulation of advanced glycation end products (AGEs) is involved in several pathophysiological processes in the vessel wall. We hypothesized that low levels of the soluble receptor for AGEs (sRAGE) might be associated with increased arterial stiffness, a manifestation of vascular ageing in the general population. Using a cross-sectional design, we analyzed 1077 subjects from the Czech post-MONICA study. The aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples using enzyme-linked immunosorbent assay methods (R&D Systems). aPWV significantly (P<0.0001) increased across the sRAGE quartiles. An aPWV of 1 m s(-1) was associated with a 37% increase in the risk of low sRAGE (<918 pg ml(-1), bottom quartile; P-value=0.018). In a categorized manner, subjects in the bottom sRAGE quartile had an odds ratio of an increased aPWV (⩾9.3 m s(-1)), adjusted for all potential confounders of 2.05 (95% confidence interval: 1.26-3.32; P=0.004), but this was only the case for non-diabetic hypertensive patients. In contrast, a low sRAGE was rejected as an independent predictor of an increased aPWV in normotensive or diabetic subjects using similar regression models. In conclusion, low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but this was only observed in hypertensive non-diabetic patients. PMID:26631850

  7. 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

  8. Subclinical Hypothyroidism Might Increase the Risk of Postoperative Atrial Fibrillation after Aortic Valve Replacement.

    PubMed

    Martínez-Comendador, Jose; Marcos-Vidal, Jose Miguel; Gualis, Javier; Martin, Carlos Esteban; Martin, Elio; Otero, Javier; Castaño, Mario

    2016-08-01

    Background To evaluate the influence of subclinical hypothyroidism (SCH) on the development of postoperative atrial fibrillation (AF) in patients undergoing aortic valve replacement surgery with extracorporeal circulation. Methods A prospective study in a tertiary hospital between July 2005 and December 2013 in which all patients undergoing aortic valve replacement with no other valve surgery were consecutively included. Patients who were in preoperative sinus rhythm were selected and they underwent thyroxine (T4) and thyroid-stimulating hormone determination in the month before surgery. Postoperative AF was defined as the development of AF during hospital admittance. Descriptive analysis and binary logistic regression were performed for the target variable. Results A total of 467 patients were studied, with 35 cases of SCH. The incidence of postoperative AF was 57% in the group with SCH versus 30.3% (p = 0.001) in the group without hypothyroidism, without significant differences in other postoperative complications. In the logistic regression analysis, the independent predictors of postoperative AF were SCH, age, and aortic clamping time. SCH multiplies the odds ratio of postoperative AF by 3.14 (95% confidence interval: 1.24-7.96). Conclusion SCH behaves like a risk factor for the development of postoperative AF in patients undergoing aortic valve replacement with extracorporeal circulation. Other studies are needed to determine whether preoperative T4 replacement therapy and/or more aggressive AF prophylaxis can prevent this complication in patients undergoing aortic valve replacement. PMID:26121379

  9. Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

    PubMed Central

    Ruseva, Boryana; Atanasova, Milena; Tsvetkova, Reni; Betova, Tatyana; Mollova, Margarita; Alexandrova, Margarita; Laleva, Pavlina; Dimitrova, Aneliya

    2015-01-01

    Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR. PMID:26473024

  10. 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

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

    PubMed Central

    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

  12. Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms

    PubMed Central

    Malkawi, Amir; Pirianov, Grisha; Torsney, Evelyn; Chetter, Ian; Sakalihasan, Natzi; Loftus, Ian M.; Nordon, Ian; Huggins, Christopher; Charolidi, Nicoletta; Thompson, Matt; Xu, Xie Yun; Cockerill, Gillian W.

    2015-01-01

    Background Since aortic diameter is the most ­significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture. Materials and Methods We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high- and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples). Results The sole significant candidate from this analysis, Lamin A/C, was validated at the protein level, using western blotting. Lamin A/C expression in the inferior mesenteric vein (IMV) of AAA patients was compared to a control group and in aortic smooth muscle cells in culture in response to physiological pulsatile stretch. ­Areas of high wall stress (n = 7) correlate to those ­regions which have the thinnest walls [778 µm (585–1120 µm)] in comparison to areas of lowest wall stress [1620 µm (962–2919 µm)]. Induced expression of Lamin A/C ­correlated with areas of high wall stress from AAAs but was not significantly induced in the IMV from AAA patients compared to controls (n = 16). Stress-induced expression of Lamin A/C was mimicked by exposing aortic smooth muscle cells to prolonged pulsatile stretch. Conclusion Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms. PMID:27175366

  13. 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 %.

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

    PubMed

    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 %. PMID:26546312

  15. Transcatheter aortic valve implantation

    PubMed Central

    Oliemy, Ahmed

    2014-01-01

    Transcatheter aortic valve implantation was developed to offer a therapeutic solution to patients with severe symptomatic aortic stenosis who are not candidates for conventional aortic valve replacement. The improvement in transcatheter aortic valve implantation outcomes is still of concern in the areas of stroke, vascular injury, heart block, paravalvular regurgitation and valve durability. Concomitantly, the progress, both technical and in terms of material advances of transcatheter valve systems, as well as in patient selection, renders transcatheter aortic valve implantation an increasingly viable treatment for more and more patients with structural heart disease. PMID:25374670

  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. 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

    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

  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. 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

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

    PubMed Central

    Förstermann, Ulrich; Li, Huige

    2011-01-01

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

  1. Aortic insufficiency

    MedlinePlus

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

  2. Aortic Aneurysm

    MedlinePlus

    ... chest and abdomen. There are two types of aortic aneurysm: Thoracic aortic aneurysms - these occur in the part of the aorta running through the chest Abdominal aortic aneurysms - these occur in the part of the aorta ...

  3. Aortic Aneurysm

    MedlinePlus

    ... chest and abdomen. There are two types of aortic aneurysm: Thoracic aortic aneurysms (TAA) - these occur in the part of the aorta running through the chest Abdominal aortic aneurysms (AAA) - these occur in the part of the ...

  4. Aortic insufficiency

    MedlinePlus

    Aortic valve prolapse; Aortic regurgitation ... Any condition that prevents the aortic valve from closing completely can cause this problem. When the valve doesn't close all the way, a small amount of blood comes ...

  5. Mechanisms of Improved Aortic Stiffness by Arotinolol in Spontaneously Hypertensive Rats

    PubMed Central

    Zhou, Wugang; Hong, Mona; Zhang, Ke; Chen, Dongrui; Han, Weiqing; Shen, Weili; Zhu, Dingliang; Gao, Pingjin

    2014-01-01

    Objectives This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR). Methods The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d-1), arotinolol (30 mg·kg-1·d-1) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting. Results Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol. Conclusions Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries. PMID:24533142

  6. 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

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

    PubMed Central

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

    2015-01-01

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

  8. 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.

  9. Recent advances in aortic valve disease: highlights from a bicuspid aortic valve to transcatheter aortic valve replacement.

    PubMed

    Augoustides, John G T; Wolfe, Yanika; Walsh, Elizabeth K; Szeto, Wilson Y

    2009-08-01

    There have been major advances in the management of aortic valve disease. Because bicuspid aortic valve is common and predicts an increased risk of adverse aortic events, these patients merit aortic surveillance and consideration for ascending aortic replacement when its diameter exceeds 4.0 cm. Serial quantitative echocardiographic analysis, as compared with traditional clinical markers, can result in better timing of surgical intervention for aortic regurgitation. Furthermore, echocardiographic analysis of aortic regurgitation can classify the mechanism based on cusp mobility to guide aortic valve repair. In aortic root replacement, aortic valve preservation with reimplantation is a mainstream surgical option in Marfan syndrome to offer freedom from valve-related anticoagulation. Prosthetic aortic root replacement has further alternatives with the introduction of the aortic neosinus design and acceptable clinical outcomes with the porcine xenograft. Because aortic valve prosthesis-patient mismatch (PPM) may adversely affect patient outcome, its perioperative prevention is important. Furthermore, significant functional mitral regurgitation in association with aortic stenosis often resolves after aortic valve replacement. Echocardiographic assessment of the aortic valve must include valve area because the transaortic pressure gradient may be low in severe stenosis. Aortic valve replacement with partial sternotomy is safe and offers a reasonable less invasive alternative. Transcatheter aortic valve replacement, whether transfemoral or transapical, has revolutionized aortic valve replacement; it remains a major theme in the specialty for 2009 and beyond. PMID:19497768

  10. Effect of long-term piceatannol treatment on eNOS levels in cultured endothelial cells.

    PubMed

    Kinoshita, Yosuke; Kawakami, Shinpei; Yanae, Koji; Sano, Shoko; Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko

    2013-01-18

    Piceatannol (3, 3', 4, 5'-tetrahydroxy-trans-stilbene) is a naturally occurring phytochemical found in passion fruit (Passiflora edulis) seeds. Previously, we demonstrated that piceatannol has acute vasorelaxant effects in rat thoracic aorta. It was suggested that endothelial NO synthase (eNOS) might be involved in piceatannol-induced acute vasorelaxation. Here, we investigated the expression of eNOS in EA.hy926 human umbilical vein cells after long-term treatment with piceatannol, and compared this effect with that of resveratrol, an analog of piceatannol. Long-term treatment with piceatannol up-regulated eNOS mRNA expression and increased eNOS protein expression in a dose-dependent manner. Moreover, piceatannol increased the levels of phosphorylated eNOS. Treatment with resveratrol also increased eNOS expression, but to a lesser degree than piceatannol. These findings indicate that piceatannol may improve vascular function by up-regulating eNOS expression. PMID:23246837

  11. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS deficient ApoE ko mice

    PubMed Central

    Kuhlencordt, Peter J.; Padmapriya, P.; Rützel, S.; Schödel, J.; Hu, K.; Schäfer, A.; Huang, P.L.; Ertl, G.; Bauersachs, J.

    2013-01-01

    Objective Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS. Methods/Results ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group. Conclusion Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway. PMID:18479686

  12. Increased Stiffness Is the Major Early Abnormality in a Pig Model of Severe Aortic Stenosis and Predisposes to Congestive Heart Failure in the Absence of Systolic Dysfunction

    PubMed Central

    Ishikawa, Kiyotake; Aguero, Jaume; Oh, Jae Gyun; Hammoudi, Nadjib; A Fish, Lauren; Leonardson, Lauren; Picatoste, Belén; Santos-Gallego, Carlos G; M. Fish, Kenneth; Hajjar, Roger J

    2015-01-01

    Background It remains unclear whether abnormal systolic function and relaxation are essential for developing heart failure in pathophysiology of severe aortic stenosis. Methods and Results Yorkshire pigs underwent surgical banding of the ascending aorta. The animals were followed for up to 5 months after surgery, and cardiac function was assessed comprehensively by invasive pressure–volume measurements, 3-dimensional echocardiography, echocardiographic speckle-tracking strain, and postmortem molecular and histological analyses. Pigs with aortic banding (n=6) exhibited significant left ventricular hypertrophy with increased stiffness compared with the control pigs (n=7) (end-diastolic pressure–volume relationship β: 0.053±0.017 versus 0.028±0.009 mm Hg/mL, P=0.007); however, all other parameters corresponding to systolic function, including ejection fraction, end-systolic pressure–volume relationship, preload recruitable stroke work, echocardiographic circumferential strain, and longitudinal strain, were not impaired in pigs with aortic banding. Relaxation parameters were also similar between groups. Sarcoplasmic reticulum calcium (Ca2+) ATPase protein levels in the left ventricle were similar. There were significant increases in 3-dimensional echocardiographic left atrial volumes, suggesting the usefulness of these indexes to detect increased stiffness. Right atrial pacing with a heart rate of 120 beats per minute induced increased end-diastolic pressure in pigs with aortic banding in contrast to decreased end-diastolic pressure in the control pigs. Histological evaluation revealed that increased stiffness was accompanied by cardiomyocyte hypertrophy and increased perimysial and perivascular fibrosis. Conclusion Increased stiffness is the major early pathological process that predisposes to congestive heart failure without abnormalities in systolic function and relaxation in a clinically relevant animal model of aortic stenosis. PMID:25994443

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

    PubMed

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

    2015-11-01

    Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure. PMID:25724934

  14. 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

  15. Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells

    PubMed Central

    2012-01-01

    The advanced glycation end products, namely AGEs, contribute to long-termed complications of diabetes mellitus, including macroangiopathy, where smooth muscle cells (SMC) proliferation stimulated by platelet-derived growth factor (PDGF) isoforms and insulin-like growth factor-I (IGF-I) plays an important role. The objective of the present study was to investigate the effect of an AGE-modified extracellular matrix protein on IGF-I induced SMC proliferation and on the IGF-I-IGF binding protein 4 (IGFBP-4) axis under basal conditions and after stimulation with PDGF-BB. IGF-I resulted in significantly higher thymidine incorporation in SMC seeded on AGE-modified fibronectin (AGE-FN) in comparison to cells seeded on fibronectin (FN). This augmented proliferation could not be accounted for by increased expression of IGF-IR, by decreased secretion of IGFBP-4, a binding protein that inhibits IGF-I mitogenic effects or by increased IGF-IR autophosphorylation. PDGF-BB did not modulate IGF-IR and IGFBP-4 mRNA expression in any of the substrata, however, this growth factor elicited opposite effects on the IGFBP-4 content in the conditioned media, increasing it in cells plated on FN and diminishing it in cells plated on AGE-FN. These findings suggest that one mechanism by which AGE-modified proteins is involved in the pathogenesis of diabetes-associated atherosclerosis might be by increasing SMC susceptibility to IGF-I mitogenic effects. PMID:22553932

  16. 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. PMID:25982099

  17. 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

  18. 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.

  19. Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.

    PubMed Central

    Li, Zhuowei; Carter, Jacqueline D; Dailey, Lisa A; Huang, Yuh-Chin T

    2004-01-01

    Exposure to excessive vanadium occurs in some occupations and with consumption of some dietary regimens for weight reduction and body building. Because vanadium is vasoactive, individuals exposed to excessive vanadium may develop adverse vascular effects. We have previously shown that vanadyl sulfate causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of nitric oxide production. In the present study we investigated whether NO inhibition was related to phosphorylation of endothelial nitric oxide synthase (eNOS). VOSO4 produced dose-dependent constriction of pulmonary arteries in isolated perfused lungs and pulmonary arterial rings and a right shift of the acetylcholine-dependent vasorelaxation curve. VOSO4 inhibited constitutive as well as A23187-stimulated NO production. Constitutive NO inhibition was accompanied by increased Thr495 (threonine at codon 495) phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and inhibition of NO were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor. There were no changes in Ser1177 (serine at codon 1177) or tyrosine phosphorylation of eNOS. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated in part by the inhibition of endothelial NO production via PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive vanadium may contribute to pulmonary vascular diseases. PMID:14754574

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Segmental Aortic Stiffening Contributes to Experimental Abdominal Aortic Aneurysm Development

    PubMed Central

    Raaz, Uwe; Zöllner, Alexander M.; Schellinger, Isabel N.; Toh, Ryuji; Nakagami, Futoshi; Brandt, Moritz; Emrich, Fabian C.; Kayama, Yosuke; Eken, Suzanne; Adam, Matti; Maegdefessel, Lars; Hertel, Thomas; Deng, Alicia; Jagger, Ann; Buerke, Michael; Dalman, Ronald L.; Spin, Joshua M.; Kuhl, Ellen; Tsao, Philip S.

    2015-01-01

    Background Stiffening of the aortic wall is a phenomenon consistently observed in age and in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. Methods and Results Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening (SAS) precedes aneurysm growth. Finite element analysis (FEA) reveals that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) wall stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent aortic segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with reduced segmental stiffness of the AAA-prone aorta (due to equalized stiffness in adjacent segments), reduced axial wall stress, decreased production of reactive oxygen species (ROS), attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, as well as attenuated apoptosis within the aortic wall. Cyclic pressurization of segmentally stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix (ECM) remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. Conclusions The present study introduces the novel concept of segmental aortic stiffening (SAS) as an early pathomechanism generating aortic wall stress and triggering aneurysmal growth, thereby delineating potential underlying molecular mechanisms and therapeutic targets. In addition, monitoring SAS may aid the identification of patients at risk for AAA. PMID:25904646

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

    PubMed

    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

  6. 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

  7. 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. PMID:22068608

  8. Angiotensin II Induces an Increase in Matrix Metalloproteinase 2 Expression in Aortic Smooth Muscle Cells of Ascending Thoracic Aortic Aneurysms Through JNK, ERK1/2, and p38 MAPK Activation.

    PubMed

    Wang, Chunmao; Chang, Qian; Sun, Xiaogang; Qian, Xiangyang; Liu, Penghong; Pei, Huawei; Guo, Xiaobo; Liu, Wenzhi

    2015-09-01

    In this study, we hypothesized that angiotensin II (Ang II) induces matrix metalloproteinase 2 (MMP-2) upregulation in aneurysmal smooth muscle cells (ASMCs) derived from ascending thoracic aortic aneurysms (ATAAs). We compared MMP-2 protein levels in ascending aortic specimens using Western blot and plasma concentrations by enzyme-linked immunosorbent assay between ATAA (n = 40) and coronary heart disease patients (n = 40). Additionally, the protein level of angiotensinogen (AGT) in the ascending aorta and the plasma concentration of Ang II were detected by Western blot and radioimmunoassay, respectively, in ATAA and coronary heart disease patients. In ATAA patients, Ang II and MMP-2 plasma levels were significantly increased (P < 0.05). Additionally, AGT and MMP-2 protein levels in the aorta of ATAA patients were higher (P < 0.01). Enhanced AGT suggested that the amount of Ang II in aneurysmal aorta specimens may be also increased, which was confirmed by immunofluorescent staining for Ang II. Moreover, we investigated the effect of Ang II on MMP-2 upregulation by ASMCs and determined the Ang II receptors and intracellular signaling pathways that are involved. Our results showed that treatment with Ang II significantly increased the expression of MMP-2 through the Ang II type 1 receptor (AT1R) and activated the 3 major mitogen-activated protein kinases (MAPKs), JNK, ERK1/2, and p38 MAPK. In conclusion, these results indicate that Ang II can induce MMP-2 expression elevation through AT1R and MAPK pathways in ASMCs and suggest that there is therapeutic potential for angiotensin receptor blocker drugs and MAPK inhibitors in the prevention and treatment of ATAAs. PMID:25955575

  9. 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

  10. Chronic vagal nerve stimulation prevents high-salt diet-induced endothelial dysfunction and aortic stiffening in stroke-prone spontaneously hypertensive rats.

    PubMed

    Chapleau, Mark W; Rotella, Diane L; Reho, John J; Rahmouni, Kamal; Stauss, Harald M

    2016-07-01

    Parasympathetic activity is often reduced in hypertension and can elicit anti-inflammatory mechanisms. Thus we hypothesized that chronic vagal nerve stimulation (VNS) may alleviate cardiovascular end-organ damage in stroke-prone spontaneously hypertensive rats. Vagal nerve stimulators were implanted, a high-salt diet initiated, and the stimulators turned on (VNS, n = 10) or left off (sham, n = 14) for 4 wk. Arterial pressure increased equally in both groups. After 4 wk, endothelial function, assessed by in vivo imaging of the long posterior ciliary artery (LPCA) after stimulation (pilocarpine) and inhibition (N(ω)-nitro-l-arginine methyl ester) of endothelial nitric oxide synthase (eNOS), had significantly declined (-2.3 ± 1.2 μm, P < 0.05) in sham, but was maintained (-0.7 ± 0.8 μm, nonsignificant) in VNS. Furthermore, aortic eNOS activation (phosphorylated to total eNOS protein content ratio) was greater in VNS (0.83 ± 0.07) than in sham (0.47 ± 0.08, P < 0.05). After only 3 wk, ultrasound imaging of the aorta demonstrated decreased aortic strain (-9.7 ± 2.2%, P < 0.05) and distensibility (-2.39 ± 0.49 1,000/mmHg, P < 0.05) and increased pulse-wave velocity (+2.4 ± 0.7 m/s, P < 0.05) in sham but not in VNS (-3.8 ± 3.8%, -0.70 ± 1.4 1,000/mmHg, and +0.1 ± 0.7 m/s, all nonsignificant). Interleukin (IL)-6 serum concentrations tended to be higher in VNS than in sham (34.3 ± 8.3 vs. 16.1 ± 4.6 pg/ml, P = 0.06), and positive correlations were found between NO-dependent relaxation of the LPCA and serum levels of IL-6 (r = +0.70, P < 0.05) and IL-10 (r = +0.56, P < 0.05) and between aortic eNOS activation and IL-10 (r = +0.48, P < 0.05). In conclusion, chronic VNS prevents hypertension-induced endothelial dysfunction and aortic stiffening in an animal model of severe hypertension. We speculate that anti-inflammatory mechanisms may contribute to these effects. PMID:27208157

  11. Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice

    PubMed Central

    Champion, Hunter C.; Bivalacqua, Trinity J.; Greenberg, Stanley S.; Giles, Thomas D.; Hyman, Albert L.; Kadowitz, Philip J.

    2002-01-01

    It has been shown that mice deficient in the gene coding for endothelial nitric-oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary vascular resistance. In the present study, the effect of transfer to the lung of an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial pressure and pulmonary vascular resistance was investigated in eNOS-deficient mice. One day after intratracheal administration of AdCMVeNOS to eNOS−/− mice, there was an increase in eNOS protein, cGMP levels, and calcium-dependent conversion of l-arginine to l-citrulline in the lung. The increase in eNOS protein and activity in eNOS−/− mice was associated with a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance when compared with values in eNOS-deficient mice treated with vehicle or a control adenoviral vector coding for β-galactosidase, AdCMVβgal. These data suggest that in vivo gene transfer of eNOS to the lung in eNOS−/− mice can increase eNOS staining, eNOS protein, calcium-dependent NOS activity, and cGMP levels and partially restore pulmonary arterial pressure and pulmonary vascular resistance to near levels measured in eNOS+/+ mice. Thus, the major finding in this study is that in vivo gene transfer of eNOS to the lung in large part corrects a genetic deficiency resulting from eNOS deletion and may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders in which eNOS activity is reduced. PMID:12237402

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

    PubMed

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

    2015-10-01

    The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities. PMID:26214584

  13. 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 ...

  14. 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, ...

  15. 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

  16. 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

  17. 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

  18. Predictive factors for increased aortic pulse wave velocity in renal transplant recipients and its relation to graft outcome.

    PubMed

    Ayub, Muazam; Ullah, Kifayat; Masroor, Imtiaz; Butt, Ghias Uddin

    2015-11-01

    To evaluate aortic stiffness in renal transplant patients and to determine the correlation of renal insufficiency and estimated glomerular filtration rate (eGFR) with aortic pulse wave velocity (APWV), we studied 96 renal transplant patients followed-up at our center. We measured the APWV using transcutaneous Doppler flow recordings and the foot-to-foot method, and calculated the eGFR using the Modification of Diet in Renal Disease equation. The study included 81 (84.4%) males and 15 (15.6%) females. The mean age of the patients was 37.84 ± 10.10 years. The mean duration of transplant was 47.90 ± 34.40 months. The eGFR of the patients ranged from 1 to 120 mL/min, with a mean GFR of 72.6 ± 23.2 mL/min. Sixty-seven (69.8%) patients had eGFR > 60 mL/min and hence had stages 1 and 2 chronic kidney disease (CKD), 27 (28.1%) patients had eGFR 30-60 mL/min and hence had stage 3 CKD and two (2.1%) patients had eGFR <30 mL/min and hence had stages 4 and 5 CKD. The APWV of the patients ranged from 4 to 14.2 m/s, with a mean of 7.49 ± 2.47 m/s. A significant inverse correlation was found between the APWV and eGFR (Pearson correlation coefficient, -0.427, P = 0.00). The mean APWV was significantly higher among patients with higher CKD stage, P = 0.004. We conclude that the APWV is related to the renal graft dysfunction as measured by eGFR. The poorer the renal function, the higher was the APWV. Determination of the APWV may be helpful in predicting the outcome in renal transplant recipients. PMID:26586049

  19. 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.

  20. Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality Implications.

    PubMed

    London, Gérard M; Safar, Michel E; Pannier, Bruno

    2016-06-01

    Aging incurs aortic stiffening and dilation, but these changes are less pronounced in peripheral arteries, resulting in stiffness and geometry gradients influencing progression of the forward and reflected pressure waves. Because premature arterial aging is observed in ESRD, we determined the respective roles of stiffness and aortic geometry gradients in 73 controls and 156 patients on hemodialysis. We measured aortic pulse wave velocity (PWV) and brachial PWV to evaluate the stiffness gradient [(brachial PWV/aortic PWV)(0.5)] and ascending aortic and aortic bifurcation diameters to assess aortic taper (ascending aortic diameter/aortic bifurcation diameter). The global reflection coefficient was estimated from characteristic impedance and vascular resistance. Cox proportional hazard models were used to determine mortality risk. The age-associated increase in aortic PWV was higher in patients (P<0.001). In controls, aortic ascending and bifurcation diameters increased with age, with an unchanged aortic taper. In patients on hemodialysis, age did not associate with increased ascending aortic diameter but did associate with increased aortic bifurcation diameter and decreased aortic taper, both of which also associated with abdominal aortic calcifications and smaller global reflection coefficient (P<0.001). In patients, multivariate models revealed all-cause and cardiovascular mortality associated with age, aortic PWV, and aortic bifurcation diameter with high specificity and sensitivity. Using stiffness gradient, aortic taper, or global reflection coefficient in the model produced similar results. Thus, whereas aortic stiffness is a known independent predictor of mortality, these results indicate the importance of also evaluating the aortic geometry in patients on hemodialysis. PMID:26475595

  1. [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

  2. Abdominal Aortic Aneurysms

    PubMed Central

    Fortner, George; Johansen, Kaj

    1984-01-01

    Aneurysms are common in our increasingly elderly population, and are a major threat to life and limb. Until the advent of vascular reconstructive techniques, aneurysm patients were subject to an overwhelming risk of death from exsanguination. The first successful repair of an abdominal aortic aneurysm using an interposed arterial homograft was reported by Dubost in 1952. A milestone in the evolution of vascular surgery, this event and subsequent diagnostic, operative and prosthetic graft refinements have permitted patients with an unruptured abdominal aortic aneurysm to enjoy a better prognosis than patients with almost any other form of major systemic illness. Images PMID:6702193

  3. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction

    PubMed Central

    LI, PENG; ZHANG, LINA; ZHANG, MEI; ZHOU, CHANGYONG; LIN, NAN

    2016-01-01

    The mechanism by which hyperuricemia induced-endothelial dysfunction contributes to cardiovascular diseases (CVDs) is not yet fully understood. In the present study, we used uric acid (UA) to trigger endothelial dysfunction in cultured endothelial cells, and investigated the effects of induced reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress induction, and the protein kinase C (PKC)-dependent endothelial nitric oxide synthase (eNOS) signaling pathway. Human umbilical vein endothelial cells (HUVECs) were incubated with 6, 9 or 12 mg/dl UA, ROS scavenger polyethylene glycol-superoxide dismutase (PEG-SOD), ER stress inhibitor 4-phenylbutyric acid (4-PBA), and PKC inhibitor polymyxin B for 6–48 h. Nitric oxide (NO) production, eNOS activity, intracellular ROS, ER stress levels, and the interaction between eNOS and calmodulin (CaM) and cytosolic calcium levels were assessed using fluorescence microscopy and western blot analysis. Apoptosis was assessed by annexin V staining. UA increased HUVEC apoptosis and reduced eNOS activity and NO production in a dose- and time-dependent manner. Intracellular ROS was elevated after 3 h, while ER stress level increased after 6 h. UA did not alter intracellular Ca2+, CaM, or eNOS concentration, or eNOS Ser1177 phosphorylation. However, PKC-dependent eNOS phosphorylation at Thr495 was greatly enhanced, and consequently interaction between eNOS and CaM was reduced. Cellular ROS depletion, ER stress inhibition and PKC activity reduction inhibited the effect of UA on eNOS activity, NO release and apoptosis in HUVECs. Thus, we concluded that UA induced HUVEC apoptosis and endothelial dysfunction by triggering oxidative and ER stress through PKC/eNOS-mediated eNOS activity and NO production. PMID:26935704

  4. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    PubMed

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions. PMID:22041135

  5. Hemodynamic Changes Quantified in Abdominal Aortic Aneurysms with Increasing Exercise Intensity Using MR Exercise Imaging and Image-Based Computational Fluid Dynamics

    PubMed Central

    Suh, Ga-Young; Les, Andrea S.; Tenforde, Adam S.; Shadden, Shawn C.; Spilker, Ryan L.; Yeung, Janice J.; Cheng, Christopher P.; Herfkens, Robert J.; Dalman, Ronald L.; Taylor, Charles A.

    2012-01-01

    Abdominal aortic aneurysm (AAA) is a vascular disease resulting in a permanent, localized enlargement of the abdominal aorta. We previously hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise. To quantify the effect of exercise intensity on hemodynamic conditions in 10 AAA subjects at rest and during mild and moderate intensities of lower-limb exercise (defined as 33 ± 10% and 63 ± 18% increase above resting heart rate, respectively), we used magnetic resonance imaging and computational fluid dynamics techniques. Subject-specific models were constructed from magnetic resonance angiography data and physiologic boundary conditions were derived from measurements made during dynamic exercise. We measured the abdominal aortic blood flow at rest and during exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and particle residence time (PRT). We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise, and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level, suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs. PMID:21509633

  6. Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice

    PubMed Central

    Massion, P B; Balligand, J-L

    2003-01-01

    The modulatory role of endothelial nitric oxide synthase (eNOS) on heart contraction, relaxation and rate is examined in light of recent studies using genetic deletion or overexpression in mice under specific conditions. Unstressed eNOS-/- hearts in basal conditions exhibit a normal inotropic and lusitropic function, with either decreased or unchanged heart rate. Under stimulation with catecholamines, eNOS-/- mice predominantly show a potentiation in their β-adrenergic inotropic and lusitropic responsiveness. A similar phenotype is observed in β3-adrenoceptor deficient mice, pointing to a key role of this receptor subtype for eNOS coupling. The effect of eNOS on the muscarinic cholinergic modulation of cardiac function probably operates in conjunction with other NO-independent mechanisms, the persistence of which may explain the apparent dispensability of this isoform for the effect of acetylcholine in some eNOS-/- mouse strains. eNOS-/- hearts submitted to short term ischaemia-reperfusion exhibit variable alterations in systolic and diastolic function and infarct size, while those submitted to myocardial infarction present a worsened ventricular remodelling, increased 1 month mortality and loss of benefit from ACE inhibitor or angiotensin II type I receptor antagonist therapy. Although non-conditional eNOS gene deletion may engender phenotypic adaptations (e.g. ventricular hypertrophy resulting from chronic hypertension, or upregulation of the other NOS isoforms) potentially confounding the interpretation of comparative studies, the use of eNOS-/- mice has undoubtedly advanced (and will probably continue to improve) our understanding of the complex role of eNOS (in conjunction with the other NOSs) in the regulation of cardiac function. The challenge is now to confirm the emerging paradigms in human cardiac physiology and hopefully translate them into therapy. PMID:12509479

  7. Participation of oleic acid in the formation of the aortic aneurysm in Marfan syndrome patients.

    PubMed

    Soto, María Elena; Iturriaga Hernández, Alejandra Valeria; Guarner Lans, Verónica; Zuñiga-Muñoz, Alejandra; Aranda Fraustro, Alberto; Velázquez Espejel, Rodrigo; Pérez-Torres, Israel

    2016-03-01

    Marfan syndrome (MFS) is associated with progressive aortic dilatation and endothelial dysfunction that lead to early acute dissection and rupture of the aorta and sudden death. Alteration in fatty acid (FA) metabolism can stimulate nitric oxide (NO) overproduction which increases the activity of the inducible form of NO synthase (iNOS) that is involved in endothelial dysfunction. We evaluated the participation of FA in the formation of thoracic aneurysms in MFS and its relation to the iNOS. Oleic acid (OA), iNOS, citrulline, nitrates and nitrites, TGF-β1, TNF-α, monounsaturated FA and NO synthase activity were significantly increased (p<0.05) in tissue from the aortas of MFS. Saturated FA, eNOS and HDL were significantly decreased (p<0.05). Arachidonic acid, delta-9 desaturase tended to increase and histological examination showed an increase in cystic necrosis, elastic fibers and collagen in MFS. The increase in OA contributes to the altered pathway of iNOS, which favors endothelial dysfunction and formation of the aortic aneurysms in MFS. PMID:27163200

  8. Ursolic acid from the Chinese herb danshen (Salvia miltiorrhiza L.) upregulates eNOS and downregulates Nox4 expression in human endothelial cells.

    PubMed

    Steinkamp-Fenske, Katja; Bollinger, Larissa; Völler, Natalie; Xu, Hui; Yao, Ying; Bauer, Rudolf; Förstermann, Ulrich; Li, Huige

    2007-11-01

    Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the most commonly used traditional Chinese medicines for cardiovascular indications. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVEC), an aqueous extract of danshen, and also a methanol extract of the plant, increased eNOS promoter activity, eNOS mRNA and protein expression, as well as endothelial NO production. A dichloromethane extract, in contrast, did not change eNOS gene expression. Thus, the active danshen constituent(s) responsible for eNOS upregulation is (are) hydrophilic and/or alcohol-soluble. One such compound is ursolic acid that significantly increased eNOS expression in EA.hy 926 cells and native HUVEC, and enhanced bioactive NO production measured in terms of its cGMP increasing activity. Other tested hydrophilic and alcohol-soluble compounds isolated from danshen had no effect on eNOS expression. Interestingly, ursolic acid also reduced the expression of the NADPH oxidase subunit Nox4 and suppressed the production of reactive oxygen species in human endothelial cells. Upregulation of eNOS and a parallel downregulation of Nox4 lead to an increase in bioactive NO. This in turn could mediate some of the beneficial effects of danshen. Ursolic acid is a prototypical compound responsible for this effect of the plant. PMID:17481637

  9. L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation.

    PubMed

    Siamwala, Jamila H; Dias, Paul M; Majumder, Syamantak; Joshi, Manoj K; Sinkar, Vilas P; Banerjee, Gautam; Chatterjee, Suvro

    2013-03-01

    Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca(2+) and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea. PMID:22819553

  10. 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

  11. Multi-resolution analysis for ENO schemes

    NASA Technical Reports Server (NTRS)

    Harten, Ami

    1991-01-01

    Given an function, u(x), which is represented by its cell-averages in cells which are formed by some unstructured grid, we show how to decompose the function into various scales of variation. This is done by considering a set of nested grids in which the given grid is the finest, and identifying in each locality the coarsest grid in the set from which u(x) can be recovered to a prescribed accuracy. This multi-resolution analysis was applied to essentially non-oscillatory (ENO) schemes in order to advance the solution by one time-step. This is accomplished by decomposing the numerical solution at the beginning of each time-step into levels of resolution, and performing the computation in each locality at the appropriate coarser grid. An efficient algorithm for implementing this program in the 1-D case is presented; this algorithm can be extended to the multi-dimensional case with Cartesian grids.

  12. 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

  13. Efficient implementation of weighted ENO schemes

    NASA Technical Reports Server (NTRS)

    Jiang, Guang-Shan; Shu, Chi-Wang

    1995-01-01

    In this paper, we further analyze, test, modify and improve the high order WENO (weighted essentially non-oscillatory) finite difference schemes of Liu, Osher and Chan. It was shown by Liu et al. that WENO schemes constructed from the r-th order (in L1 norm) ENO schemes are (r+1)-th order accurate. We propose a new way of measuring the smoothness of a numerical solution, emulating the idea of minimizing the total variation of the approximation, which results in a 5-th order WENO scheme for the case r = 3, instead of the 4-th order with the original smoothness measurement by Liu et al. This 5-th order WENO scheme is as fast as the 4-th order WENO scheme of Liu et al., and both schemes are about twice as fast as the 4-th order ENO schemes on vector supercomputers and as fast on serial and parallel computers. For Euler systems of gas dynamics, we suggest computing the weights from pressure and entropy instead of the characteristic values to simplify the costly characteristic procedure. The resulting WENO schemes are about twice as fast as the WENO schemes using the characteristic decompositions to compute weights, and work well for problems which do not contain strong shocks or strong reflected waves. We also prove that, for conservation laws with smooth solutions, all WENO schemes are convergent. Many numerical tests, including the 1D steady state nozzle flow problem and 2D shock entropy wave interaction problem, are presented to demonstrate the remarkable capability of the WENO schemes, especially the WENO scheme using the new smoothness measurement, in resolving complicated shock and flow structures. We have also applied Yang's artificial compression method to the WENO schemes to sharpen contact discontinuities.

  14. 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

  15. Aortic regurgitation after transcatheter aortic valve replacement.

    PubMed

    Werner, Nikos; Sinning, Jan-Malte

    2014-01-01

    Paravalvular aortic regurgitation (AR) negatively affects prognosis following transcatheter aortic valve replacement (TAVR). As transcatheter heart valves (THV) are anchored using a certain degree of oversizing at the level of the aortic annulus, incomplete stent frame expansion because of heavily annular calcifications, suboptimal placement of the prosthesis, and/or annulus-prosthesis size-mismatch can contribute to paravalvular AR with subsequent increased mortality risk. Echocardiography is essential to differentiate between transvalvular and paravalvular AR and to further elucidate the etiology of AR during the procedure. However, because echocardiographic quantification of AR in TAVR patients remains challenging, especially in the implantation situation, a multimodal approach to the evaluation of AR with use of hemodynamic measurements and imaging modalities is useful to precisely quantify the severity of AR immediately after valve deployment. "Next-generation" THVs are already on the market and first results show that paravalvular AR related to design modifications (eg, paravalvular space-fillers, full repositionability) are rarely seen in these valve types.  PMID:24632758

  16. 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

  17. 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

  18. 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 ...

  19. Thoracic aortic aneurysm

    MedlinePlus

    Aortic aneurysm - thoracic; Syphilitic aneurysm; Aneurysm - thoracic aortic ... The most common cause of a thoracic aortic aneurysm is hardening of the ... with high cholesterol, long-term high blood pressure, or who ...

  20. Altered VEGF-stimulated Ca2+ signaling in part underlies pregnancy-adapted eNOS activity in UAEC.

    PubMed

    Boeldt, Derek S; Grummer, Mary A; Magness, Ronald R; Bird, Ian M

    2014-10-01

    In pregnancy, the uterine vasculature undergoes dramatic vasodilatory adaptations. Previously, vascular endothelial growth factor (VEGF) has been shown to stimulate endothelial nitric oxide synthase (eNOS) in uterine artery endothelial cells (UAECs) derived from pregnant ewes to a greater extent than those from non-pregnant ewes in a manner not fully explained by changes in the phosphorylation of eNOS. In this study, we used Fura-2 Ca(2+) imaging and arginine-to-citrulline conversion eNOS activity assays to assess the importance of VEGF-stimulated Ca(2+) responses in pregnancy-related changes in NO production in UAEC. In this study, we show that pregnancy-induced changes in VEGF-stimulated Ca(2+) responses could account in part for the greater capacity of VEGF to stimulate eNOS in UAECs from pregnant versus non-pregnant animals. VEGF-stimulated Ca(2+) responses in UAECs from pregnant and non-pregnant animals were mediated through VEGF receptor 2 and were detected in roughly 15% of all cells. There were no pregnancy-specific differences in area under the curve or peak height. UAECs from pregnant animals were more consistent in the time to response initiation, had a larger component of extracellular Ca(2+) entry, and were more sensitive to a submaximal dose of VEGF. In UAECs from pregnant and non-pregnant animals Ca(2+) responses and eNOS activation were sensitive to the phospholipase C/inositol 1,4,5-trisphosphate pathway inhibitors 2-aminoethoxydiphenylborane and U73122. Thus, changes in VEGF-stimulated [Ca(2+)]i are necessary for eNOS activation in UAECs, and pregnancy-induced changes in Ca(2+) responses could also in part explain the pregnancy-specific adaptive increase in eNOS activity in UAECs. PMID:25063757

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

    PubMed Central

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

    2013-01-01

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

  2. 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

  3. 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

  4. AB037. Icariside II improves human cavernous endothelial cells function by regulating miR-155/eNOS signal pathway

    PubMed Central

    Guan, Ruili; Lei, Hongen; Yang, Bicheng; Li, Huixi; Wang, Lin; Guo, Yinglu; Xin, Zhongcheng

    2016-01-01

    Background To investigate the changes of miR-155/endothelial nitric oxide synthase (eNOS) signal pathway under the stimulation of age-BSA and glucose with or without icariside II (ICAII) intervention inhuman cavernous endothelial cells (HCECs). Methods Purified HCECs were first divided into three groups randomly: normal group + BSA (NC group), age-BSA + glucose group (DM group), ICAII treatment group (DM + ICAII group with different concentrations at 0.1, 1, 10 µM). Western Blot to detect the protein expression of eNOS and RAGE; real time PCR to detect the expression of miR-155 and eNOS; DAF-FM DA fluorescent probes assay and NaNO3/NaNO2 assay to detect the NO concentration. Lentivirus mediated miR-155 over-expression was constructed to observe the changes of eNOS and NO. Results The eNOS and RAGE expression in DM group is significantly reduced and increased respectively compared with that of NC group (P<0.05), while ICAII intervention could reverse this change effectively. The 10 µM of ICAII has the most powerful effect. MiR-155 has the highest fold changes among candidate miRNAs in diabetic like HCECs (P<0.05). MiR-155 increased and eNOS decreased remarkably in DM group, while ICAII intervention could inhibit the miR-155 expression, which led to the significantly higher eNOS expression and NO concentration (P<0.05). In lentivirus mediated miR-155 overexpression with or without ICAII intervention model, we found the similar trend with the above diabetic model. Conclusions MiR-155/eNOS signal pathway may be involved in the process of diabetic HCECs dysfunction. ICAII could promote the recovery of the endothelial dysfunction by regulating the miR-155/eNOS signal pathway.

  5. The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production

    PubMed Central

    Choi, Jiyea; Kim, Hyemin; Kim, Yejin; Jang, Mirim; Jeon, Jane; Hwang, Young-il; Shon, Won Jun; Song, Yeong Wook; Lee, Wang Jae

    2015-01-01

    GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation. PMID:26770183

  6. The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.

    PubMed

    Choi, Jiyea; Kim, Hyemin; Kim, Yejin; Jang, Mirim; Jeon, Jane; Hwang, Young-Il; Shon, Won Jun; Song, Yeong Wook; Kang, Jae Seung; Lee, Wang Jae

    2015-12-01

    GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation. PMID:26770183

  7. 17-beta-oestradiol-induced vasorelaxation in vitro is mediated by eNOS through hsp90 and akt/pkb dependent mechanism.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cicala, Carla; Pinto, Aldo; Cirino, Giuseppe

    2002-04-01

    1. The L-arginine-NO pathway has been implicated in the vasorelaxant effect of 17-beta-oestradiol. Here we have addressed the involvement of two distinct activation steps of endothelial nitric oxide synthase (eNOS) in the 17-beta-oestradiol-induced vasorelaxant effect on rat aortic rings. 2. Rat aortic rings contracted with phenylephrine (PE) 1 microM relaxed in a concentration related fashion to 17-beta-oestradiol water soluble cyclodextrin-encapsulated (E2) only when endothelium was present. The pure anti-oestrogen of E2 receptor ICI 182,780 (20 microM) significantly inhibited E2-induced vasorelaxation. 3. Geldanamycin (10 microM), a specific inhibitor of heat shock protein 90 (hsp90) and N(omega)-nitro-L-arginine-methyl ester (L-NAME, 100 microM), a nitric oxide synthase inhibitor, significantly inhibited E2-induced vasorelaxation. 4. Incubation of rat aortic rings up to 6 h with LY 294002 (25 microM), a specific inhibitor of PI(3)K akt/pkb pathway reduced E2-induced vasorelaxation. 5. Incubation of rat isolated aorta with E2, induced prostacyclin (PGI(2)) release. PGI(2) levels, measured as 6-keto PGF(1alpha), were abolished by ibuprofen (10 microM), both L-NAME and GA did not influence basal or E2-stimulated PGI(2) confirming the specificity of these two compounds on eNOS pathway. 6. In conclusion, we demonstrate that E2 interaction with its receptor is followed by a vasorelaxant effect in rat aortic rings mediated by eNOS activation through both hsp90 and akt/pkb dependent mechanisms. PMID:11934809

  8. 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 Central

    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

  9. Endothelial Nitric Oxide Synthase (eNOS) 4a/b and G894T Polymorphisms and Susceptibility to Preeclampsia

    PubMed Central

    Rahimi, Zohreh; Aghaei, Amir; Rahimi, Ziba; Vaisi-Raygani, Asad

    2013-01-01

    Background Preeclampsia is a pregnancy complication with unknown etiology and its incidence is associated with genetic and environmental factors. There are inconsistent reports related to the role of endothelial nitric oxide synthase (eNOS) 4a/b polymorphism on the risk of preeclampsia development. The aim of the present study was to investigate the possible influence of eNOS 4a/b and its synergism with eNOS G894T polymorphism on the risk of preeclampsia. Methods The present case-control study consisted of 179 unrelated women with preeclampsia including 118 with mild and 61 with severe preeclampsia and 96 unrelated women with normal pregnancy as controls. All studied women were from Kermanshah Province of Iran. eNOS 4a/b and G894T genotypes were detected using polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. The categorical variables between groups were compared using χ2 test and the Odds ratios (OR) were obtained by SPSS logistic regression. Statistical significance was assumed at p<0.05 level. Results The frequency of eNOS a allele was slightly higher in both mild (16.5%) and severe (17.2%) preeclamptic women than controls (15.1%). Also, no significant difference was found between early- and late-onset preeclamptic women regarding the distribution of eNOS 4a/b genotypes. The presence of each allele of eNOS a or T was not associated with the risk of preeclampsia. However, the concomitant presence of both eNOS a and T alleles was associated with a non significant increased risk of severe preeclampsia by 1.77-fold (p=0.35). Conclusion The present study indicates the lack of association between eNOS a and T alleles with the risk of mild preeclampsia and a non significant increased risk of severe preeclampsia in the presence of both alleles which needs to be investigated in a study with larger samples. PMID:24551572

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

    PubMed

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

    2016-05-01

    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

  11. When and how to replace the aortic root in type A aortic dissection

    PubMed Central

    Leshnower, Bradley G.

    2016-01-01

    Management of aortic root pathology during repair of acute type A aortic dissection (TAAD) requires a comprehensive evaluation of the patient’s anatomy, demographics, comorbidities and physiologic status at the time of emergent operative intervention. Surgical options include conservative repair of the root (CRR) (with or without replacement of the aortic valve), replacement of the native valve and aortic root using a composite valve-conduit and valve sparing root replacement (VSRR). The primary objective of this review is to provide data for surgeons to aid in their decision-making process regarding management of the aortic root during repair of TAAD. No time or language restrictions were imposed and references of the selected studies were checked for additional relevant citations. Multiple retrospective reviews have demonstrated equivalent operative mortality between aortic root repair and replacement during TAAD. There is a higher incidence of aortic root reintervention with aortic root repair compared to aortic root replacement (ARR). Experienced, high-volume aortic centers have demonstrated the safety of VSRR in young, hemodynamically stable patients presenting with TAAD. In conclusion, aortic root repair can safely be performed in the vast majority of patients with TAAD. Despite the increased surgical complexity, ARR does not increase operative mortality and improves the freedom from root reintervention. VSRR can be performed in highly selected populations of patients with TAAD with durable mid-term valve function. PMID:27563551

  12. When and how to replace the aortic root in type A aortic dissection.

    PubMed

    Leshnower, Bradley G; Chen, Edward P

    2016-07-01

    Management of aortic root pathology during repair of acute type A aortic dissection (TAAD) requires a comprehensive evaluation of the patient's anatomy, demographics, comorbidities and physiologic status at the time of emergent operative intervention. Surgical options include conservative repair of the root (CRR) (with or without replacement of the aortic valve), replacement of the native valve and aortic root using a composite valve-conduit and valve sparing root replacement (VSRR). The primary objective of this review is to provide data for surgeons to aid in their decision-making process regarding management of the aortic root during repair of TAAD. No time or language restrictions were imposed and references of the selected studies were checked for additional relevant citations. Multiple retrospective reviews have demonstrated equivalent operative mortality between aortic root repair and replacement during TAAD. There is a higher incidence of aortic root reintervention with aortic root repair compared to aortic root replacement (ARR). Experienced, high-volume aortic centers have demonstrated the safety of VSRR in young, hemodynamically stable patients presenting with TAAD. In conclusion, aortic root repair can safely be performed in the vast majority of patients with TAAD. Despite the increased surgical complexity, ARR does not increase operative mortality and improves the freedom from root reintervention. VSRR can be performed in highly selected populations of patients with TAAD with durable mid-term valve function. PMID:27563551

  13. Roles of ROS and PKC-βII in ionizing radiation-induced eNOS activation in human vascular endothelial cells.

    PubMed

    Sakata, Kimimasa; Kondo, Takashi; Mizuno, Natsumi; Shoji, Miki; Yasui, Hironobu; Yamamori, Tohru; Inanami, Osamu; Yokoo, Hiroki; Yoshimura, Naoki; Hattori, Yuichi

    2015-07-01

    Vascular endothelial cells can absorb higher radiation doses than any other tissue in the body, and post-radiation impaired endothelial nitric oxide synthase (eNOS) function may be developed as a potential contributor to the pathogenesis of vascular injury. In this study, we investigated early alterations of eNOS signaling in human umbilical venous endothelial cells (HUVECs) exposed to X-ray radiation. We found that ionizing radiation increased eNOS phosphorylation at Ser-1177 and dephosphorylation at Thr-495 in HUVECs in a dose-dependent (≤ 20 Gy) and time-dependent (6-72 h) manner. The total expression levels of eNOS were unchanged by radiation. Although a transient but significant increase in extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation and a biphasic decline in Akt phosphorylation were observed after irradiation, these inhibitors were without effect on the radiation-induced changes in eNOS phosphorylation. There was an increase in protein kinase C-βII (PKC-βII) expression and the ablation of PKC-βII by small interfering RNA (siRNA) negated the radiation effect on the two eNOS phosphorylation events. Furthermore, when the radiation-induced increase in reactive oxygen species (ROS) generation was prevented by the anti-oxidant N-acetyl-L-cysteine, eNOS Ser-1177 phosphorylation and Thr-495 dephosphorylation in irradiated HUVECs were significantly reduced. However, transfection of PKC-β siRNA did not alter ROS production after irradiation, and NAC failed to block the radiation-induced increase in PKC-βII expression. Taken together, our results suggest that ionizing radiation-induced eNOS activation in human vascular endothelial cells is attributed to both the up-regulation of PKC-βII and the increase in ROS generation which were independent of each other. PMID:25869503

  14. 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

  15. Multi-resolution analysis for ENO schemes

    NASA Technical Reports Server (NTRS)

    Harten, Ami

    1993-01-01

    Given a function u(x) which is represented by its cell-averages in cells which are formed by some unstructured grid, we show how to decompose the function into various scales of variation. This is done by considering a set of nested grids in which the given grid is the finest, and identifying in each locality the coarsest grid in the set from which u(x) can be recovered to a prescribed accuracy. We apply this multi-resolution analysis to Essentially Non-oscillatory Schemes (ENO) schemes in order to reduce the number of numerical flux computations which is needed in order to advance the solution by one time-step. This is accomplished by decomposing the numerical solution at the beginning of each time-step into levels of resolution, and performing the computation in each locality at the appropriate coarser grid. We present an efficient algorithm for implementing this program in the one-dimensional case; this algorithm can be extended to the multi-dimensional case with cartesian grids.

  16. Pregnancy after aortic root replacement in Loeys-Dietz syndrome: High risk of aortic dissection.

    PubMed

    Braverman, Alan C; Moon, Marc R; Geraghty, Patrick; Willing, Marcia; Bach, Christopher; Kouchoukos, Nicholas T

    2016-08-01

    Loeys-Dietz syndrome due to mutations in TGFBR1 and 2 is associated with early and aggressive aortic aneurysm and branch vessel disease. There are reports of uncomplicated pregnancy in this condition, but there is an increased risk of aortic dissection and uterine rupture. Women with underlying aortic root aneurysm are cautioned about the risk of pregnancy-related aortic dissection. Prophylactic aortic root replacement is recommended in women with aortopathy and aortic root dilatation to lessen the risk of pregnancy. There is limited information in the literature about the outcomes of pregnancy after root replacement in Loeys-Dietz syndrome. We present a case series of three women with Loeys-Dietz syndrome who underwent elective aortic root replacement for aneurysm disease and subsequently became pregnant and underwent Cesarean section delivery. Each of these women were treated with beta blockers throughout pregnancy. Surveillance echocardiograms and noncontrast MRA studies during pregnancy remained stable demonstrating no evidence for aortic enlargement. Despite the normal aortic imaging and careful observation, two of the three women suffered acute aortic dissection in the postpartum period. These cases highlight the high risk of pregnancy following aortic root replacement in Loeys-Dietz syndrome. Women with this disorder are recommended to be counseled accordingly. © 2016 Wiley Periodicals, Inc. PMID:27125181

  17. Thoracic Aortic Dissection: Are Matrix Metalloproteinases Involved?

    PubMed Central

    Zhang, Xiaoming; Shen, Ying H.; LeMaire, Scott A.

    2010-01-01

    Thoracic aortic dissection, one of the major diseases affecting the aorta, carries a very high mortality rate. Improving our understanding of the pathobiology of this disease may help us develop medical treatments to prevent dissection and subsequent aneurysm formation and rupture. Dissection is associated with degeneration of the aortic media. Recent studies have shown increased expression and activation of a family of proteolytic enzymes—called matrix metalloproteinases (MMPs)—in dissected aortic tissue, suggesting that MMPs may play a major role in this disease. Inhibition of MMPs may be beneficial in reducing MMP-mediated aortic damage associated with dissection. This article reviews the recent literature and summarizes our current understanding of the role of MMPs in the pathobiology of thoracic aortic dissection. The potential importance of MMP inhibition as a future treatment of aortic dissection is also discussed. PMID:19476747

  18. Aortic valve decalcification revisited.

    PubMed

    Marty, A T; Mufti, S; Murabit, I

    1989-11-01

    A 75-year-old woman with a small calcified aortic root, severe aortic stenosis and triple vessel coronary artery disease developed angina at rest. Aortic valve decalcification and quadruple aorto-coronary bypass were done as her aortic root was too small and calcified to do anything else. Postoperative clinical and hemodynamic results have been excellent. Literature review supports application of this therapy in selected patients with trileaflet senescent aortic stenosis. PMID:2614067

  19. Inhibiting LDL glycation ameliorates increased cholesteryl ester synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats

    PubMed Central

    Cohen, Margo P.; Shea, Elizabeth A.; Wu, Van-Yu

    2009-01-01

    Increased nonenzymatic glycation of apoB-containing lipoproteins impairs uptake and metabolism by the high affinity low density lipoprotein (LDL) receptor, and is one of the post-secretory modifications contributory to accelerated atherosclerosis in diabetes. The present study evaluated in vitro and in vivo effects of 2,2-chlorophenylaminophenylacetate (CAP22) to probe the influence of glycated lipoprotein on cholesterol homeostasis. This compound prevented the increased formation of glycated products in LDL incubated with 200 mM glucose and the increased cholesteryl ester synthesis in THP-1 macrophages induced by apoB-containing lipoproteins preincubated with high glucose concentration. The elevated circulating concentrations of glycated lipoprotein and cholesterol and higher vascular levels of lipid peroxidation products observed in streptozotocin diabetic rats compared to nondiabetic controls were significantly reduced in diabetic animals treated for six months with test compound. These results are the first to demonstrate that inhibiting nonenzymatic glycation of apoB-containing lipoproteins ameliorates abnormalities contributory to hypercholesterolemia and atherogenic risk in diabetes. PMID:19922964

  20. 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

  1. 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; Department of Cardiology, Karolinska University Hospital, Stockholm ; Caidahl, Kenneth; Department of Clinical Physiology, Karolinska University Hospital, Stockholm ; Franco-Cereceda, Anders; Department of Throracic Surgery, Karolinska University Hospital, Stockholm ; Baeck, Magnus; Department of Cardiology, Karolinska University Hospital, Stockholm

    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

  2. Micromanaging abdominal aortic aneurysms.

    PubMed

    Maegdefessel, Lars; Spin, Joshua M; Adam, Matti; Raaz, Uwe; Toh, Ryuji; Nakagami, Futoshi; Tsao, Philip S

    2013-01-01

    The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to "fine tune" the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility. PMID:23852016

  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. Aortic Disease Presentation and Outcome Associated with ACTA2 mutations

    PubMed Central

    Regalado, Ellen S.; Guo, Dongchuan; Prakash, Siddharth; Bensend, Tracy A.; Flynn, Kelly; Estrera, Anthony; Safi, Hazim; Liang, David; Hyland, James; Child, Anne; Arno, Gavin; Boileau, Catherine; Jondeau, Guillaume; Braverman, Alan; Moran, Rocio; Morisaki, Takayuki; Morisaki, Hiroko; Consortium, Montalcino Aortic; Pyeritz, Reed; Coselli, Joseph; LeMaire, Scott; Milewicz, Dianna M.

    2015-01-01

    Background ACTA2 mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with ACTA2 mutations. Methods and Results Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various ACTA2 mutations. Aortic events occurred in 48% of these individuals, with the vast majority presenting with thoracic aortic dissections (88%) associated with 25% mortality. Type A dissections were more common than type B dissections (54% versus 21%), but the median age of onset of type B dissections was significantly younger than type A dissections (27 years, IQR 18–41 versus 36 years, IQR 26–45). Only 12% of aortic events were repair of ascending aortic aneurysms, which variably involved the aortic root, ascending aorta and aortic arch. Overall cumulative risk of an aortic event at age 85 years was 0.76 (95% CI 0.64, 0.86). After adjustment for intra-familial correlation, gender and race, mutations disrupting p.R179 and p.R258 were associated with significantly increased risk for aortic events, whereas p.R185Q and p.R118Q mutations showed significantly lower risk of aortic events compared to other mutations. Conclusions ACTA2 mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only 76%, suggesting that additional environmental or genetic factors play a role in expression of aortic disease in individuals with ACTA2 mutations. PMID:25759435

  5. Coronary Flow Impacts Aortic Leaflet Mechanics and Aortic Sinus Hemodynamics

    PubMed Central

    Moore, Brandon L.; Dasi, Lakshmi Prasad

    2016-01-01

    Mechanical stresses on aortic valve leaflets are well-known mediators for initiating processes leading to calcific aortic valve disease. Given that non-coronary leaflets calcify first, it may be hypothesized that coronary flow originating from the ostia significantly influences aortic leaflet mechanics and sinus hemodynamics. High resolution time-resolved particle image velocimetry (PIV) measurements were conducted to map the spatiotemporal characteristics of aortic sinus blood flow and leaflet motion with and without physiological coronary flow in a well-controlled in vitro setup. The in vitro setup consists of a porcine aortic valve mounted in a physiological aorta sinus chamber with dynamically controlled coronary resistance to emulate physiological coronary flow. Results were analyzed using qualitative streak plots illustrating the spatiotemporal complexity of blood flow patterns, and quantitative velocity vector and shear stress contour plots to show differences in the mechanical environments between the coronary and non-coronary sinuses. It is shown that the presence of coronary flow pulls the classical sinus vorticity deeper into the sinus and increases flow velocity near the leaflet base. This creates a beneficial increase in shear stress and washout near the leaflet that is not seen in the non-coronary sinus. Further, leaflet opens approximately 10% farther into the sinus with coronary flow case indicating superior valve opening area. The presence of coronary flow significantly improves leaflet mechanics and sinus hemodynamics in a manner that would reduce low wall shear stress conditions while improving washout at the base of the leaflet. PMID:25636598

  6. 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

  7. Current aortic endografts for the treatment of abdominal aortic aneurysms.

    PubMed

    Colvard, Benjamin; Georg, Yannick; Chakfe, Nabil; Swanstrom, Lee

    2016-05-01

    Endovascular Aneurysm Repair is a widely adopted method of treatment for patients with abdominal aortic aneurysms. The minimally invasive approach offered with EVAR has become popular not only among physicians and patients, but in the medical device industry as well. Over the past 25 years the global market for aortic endografts has increased rapidly, resulting in a wide range of devices from various companies. Currently, there are seven endografts approved by the FDA for the treatment of abdominal aortic aneurysms. These devices offer a wide range of designs intended to increase inclusion criteria while decreasing technical complications such as endoleak and migration. Despite advances in device design, secondary interventions and follow-up requirements remain a significant issue. New devices are currently being studied in the U.S. and abroad and may significantly reduce complications and secondary interventions. PMID:26959727

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Aortic valve replacement in rheumatoid aortic incompetence.

    PubMed Central

    Devlin, A B; Goldstraw, P; Caves, P K

    1978-01-01

    Rheumatoid aortic valve disease is uncommon. and there are few reports of valve replacement in this condition. Aortic valve replacement and partial pericardiectomy was performed in a patient with acute rheumatoid aortitis and aortic incompetence. Previous reports suggest that any patient with rheumatoid arthritis who develops cardiac symptoms should be carefully assessed for surgically treatable involvement of the pericardium or heart valves. Images PMID:725829

  14. 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.

  15. Regulation of Endothelial Glutathione by ICAM-1 governs VEGF-A mediated eNOS Activity and Angiogenesis

    PubMed Central

    Langston, Will; Chidlow, John H.; Booth, Blake A.; Barlow, Shayne C.; Lefer, David J.; Patel, Rakesh P.; Kevil, Christopher G.

    2007-01-01

    Previous studies suggest that inflammatory cell adhesion molecules may modulate endothelial cell migration and angiogenesis through unknown mechanisms. Using a combination of in vitro and in vivo approaches, herein we reveal a novel redox sensitive mechanism by which ICAM-1 modulates endothelial GSH that controls VEGF-A induced eNOS activity, endothelial chemotaxis, and angiogenesis. In vivo disk angiogenesis assays showed attenuated VEGF-A mediated angiogenesis in ICAM-1−/− mice. Moreover, VEGF-A dependent chemotaxis, eNOS phosphorylation, and nitric oxide (NO) production were impaired in ICAM-1−/− MAEC compared to WT MAEC. Decreasing intracellular GSH in ICAM-1−/− MAEC to levels observed in WT MAEC with 150 μM buthionine sulfoximine (BSO) restored VEGF-A responses. Conversely, GSH supplementation of WT MAEC with 5 mM glutathione ethyl ester (GEE) mimicked defects observed in ICAM-1−/− cells. Deficient angiogenic responses in ICAM-1−/− cells were associated with increased expression of the lipid phosphatase, PTEN, consistent with antagonism of signaling pathways leading to eNOS activation. PTEN expression was also sensitive to GSH status, decreasing or increasing in proportion to intracellular GSH concentrations. These data suggest a novel role for ICAM-1 in modulating VEGF-A induced angiogenesis and eNOS activity through regulation of PTEN expression via modulation of intracellular GSH status. PMID:17291995

  16. Abdominal aortic aneurysm

    MedlinePlus

    ... to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs when an area of the aorta becomes ... blood pressure Male gender Genetic factors An abdominal aortic aneurysm is most often seen in males over age ...

  17. Aortic aneurysm repair - endovascular

    MedlinePlus

    ... Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... leaking or bleeding. You may have an abdominal aortic aneurysm that is not causing any symptoms or problems. ...

  18. Aortic aneurysm repair - endovascular

    MedlinePlus

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... leaking or bleeding. You may have an abdominal aortic aneurysm that is not causing any symptoms or problems. ...

  19. Abdominal Aortic Aneurysms: Treatments

    MedlinePlus

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

  20. Bicuspid Aortic Valve: Unlocking the Morphogenetic Puzzle.

    PubMed

    Longobardo, Luca; Jain, Renuka; Carerj, Scipione; Zito, Concetta; Khandheria, Bijoy K

    2016-08-01

    Although bicuspid aortic valve is the most common congenital abnormality, it is perhaps erroneous to consider this disease one clinical entity. Rather, it may be useful to consider it a cluster of diseases incorporating different phenotypes, etiologies, and pathogenesis. Discussion of bicuspid aortic valve can be difficult because there is no clear consensus on a phenotypic description among authors, and many classification schemes have been proposed. The literature suggests that different phenotypes have different associations and clinical manifestations. In addition, recent studies suggest a genetic basis for the disease, yet few genes have so far been described. Furthermore, recent scientific literature has been focusing on the increased risk of aortic aneurysms, but the pathogenesis of bicuspid aortic valve aortopathy is still unclear. The aim of this paper is to review the current evidence about the unsolved issues around bicuspid aortic valve. PMID:27059385

  1. 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. PMID:26682617

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

    PubMed

    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

    2016-07-01

    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

  3. Up-Regulation of ENO1 by HIF-1α in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion

    PubMed Central

    Zheng, Feihui; Jang, Wai-Chi; Fung, Frederic K. C.; Lo, Amy C. Y.; Wong, Ian Y. H.

    2016-01-01

    Purpose Alpha-enolase (ENO1), a major glycolytic enzyme, is reported to be over-expressed in various cancer tissues. It has been demonstrated to be regulated by the Hypoxia-inducible factor 1-α (HIF-1α), a crucial transcriptional factor implicated in tumor progression and cancer angiogenesis. Choroidal neovascularization (CNV), which is a leading cause of severe vision loss caused by newly formed blood vessels in the choroid, is also engendered by hypoxic stress. In this report, we investigated the expression of ENO1 and the effects of its down-regulation upon cobalt (II) chloride-induced hypoxia in retinal pigment epithelial cells, identified as the primary source of ocular angiogenic factors. Methods HIF-1α-diminished retinal pigment epithelial cells were generated by small interfering RNA (siRNA) technology in ARPE-19 cells, a human retinal pigment epithelial cell line. Both normal and HIF-1α-diminished ARPE-19 cells were then subjected to hypoxic challenge using cobalt (II) chloride (CoCl2) or anaerobic chamber. The relation between ENO1 expression and vascular endothelial growth factor (VEGF) secretion by retinal pigment epithelial cells were examined. Protein levels of HIF-1α and ENO1 were analyzed using Western Blot, while VEGF secretion was essayed by enzyme-linked immunosorbent assay (ELISA). Cytotoxicity after hypoxia was detected by Lactate Dehydrogenase (LDH) Assay. Results Upon 24 hr of CoCl2-induced hypoxia, the expression levels of ENO1 and VEGF were increased along with HIF-1α in ARPE-19 cells, both of which can in turn be down-regulated by HIF-1α siRNA application. However, knockdown of ENO1 alone or together with HIF-1α did not help suppress VEGF secretion in hypoxic ARPE-19 cells. Conclusion ENO1 was demonstrated to be up-regulated by HIF-1α in retinal pigment epithelial cells in response to hypoxia, without influencing VEGF secretion. PMID:26882120

  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. Aortic Valve Sparing in Different Aortic Valve and Aortic Root Conditions.

    PubMed

    David, Tirone E

    2016-08-01

    The development of aortic valve-sparing operations (reimplantation of the aortic valve and remodeling of the aortic root) expanded the surgical armamentarium for treating patients with aortic root dilation caused by a variety of disorders. Young adults with aortic root aneurysms associated with genetic syndromes are ideal candidates for reimplantation of the aortic valve, and the long-term results have been excellent. Incompetent bicuspid aortic valves with dilated aortic annuli are also satisfactorily treated with the same type of operation. Older patients with ascending aortic aneurysm and aortic insufficiency secondary to dilated sinotubular junction and a normal aortic annulus can be treated with remodeling of the aortic root or with reimplantation of the aortic valve. The first procedure is simpler, and both procedures are likely equally effective. As with any heart valve-preserving procedure, patient selection and surgical expertise are keys to successful and durable repairs. PMID:27491910

  6. Interleukin-6 Attenuates Insulin-Mediated Increases in Endothelial Cell Signaling but Augments Skeletal Muscle Insulin Action via Differential Effects on Tumor Necrosis Factor-α Expression

    PubMed Central

    Yuen, Derek Y.C.; Dwyer, Renee M.; Matthews, Vance B.; Zhang, Lei; Drew, Brian G.; Neill, Bronwyn; Kingwell, Bronwyn A.; Clark, Michael G.; Rattigan, Stephen; Febbraio, Mark A.

    2009-01-01

    OBJECTIVE The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS). We hypothesized that IL-6 promotes endothelial cell signaling and capillary recruitment in vivo, contributing to increased glucose uptake. RESEARCH DESIGN AND METHODS The effect of IL-6 with and without insulin on AMPK, insulin, and eNOS signaling in and nitric oxide (NO) release from human aortic endothelial cells (HAECs) was examined. The physiological significance of these in vitro signaling events was assessed by measuring capillary recruitment in rats during control and euglycemic-hyperinsulinemic clamps with or without IL-6 infusion. RESULTS IL-6 blunted increases in insulin signaling, eNOS phosphorylation (Ser1177), and NO production and reduced phosphorylation of AMPK in HAEC in vitro and capillary recruitment in vivo. In contrast, IL-6 increased Akt phosphorylation (Ser473) in hindlimb skeletal muscle and enhanced whole-body glucose disappearance and glucose uptake during the clamp. The differences in endothelial cell and skeletal muscle signaling were mediated by the cell-specific, additive effects of IL-6 and insulin because this treatment markedly increased tumor necrosis factor (TNF)-α protein expression in HAECs without any effect on TNF-α in skeletal muscle. When HAECs were incubated with a TNF-α–neutralizing antibody, the negative effects of IL-6 on eNOS signaling were abolished. CONCLUSIONS In the presence of insulin, IL-6 contributes to aberrant endothelial cell signaling because of increased TNF-α expression. PMID:19188427

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

    PubMed

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

    2015-06-01

    Aortic distensibility (AD) decreases with age and increased aortic stiffness is independently associated with adverse cardiovascular outcomes. The association of severe aortic stenosis (AS) with AD in different aortic regions has not been evaluated. Elderly subjects with severe AS and a cohort of patients without AS of similar age were studied. Proximal aortic cross-sectional-area changes during the cardiac cycle were determined using retrospective-ECG-gating on 128-detector row computed-tomography. Using oscillometric-brachial-blood-pressure measurements, the AD at the ascending-aorta (AA), proximal-descending-aorta (PDA) and distal-descending-aorta (DDA) was determined. Linear mixed effects modelling was used to determine the association of age and aortic stenosis on regional AD. 102 patients were evaluated: 36 AS patients (70-85 years), 24 AS patients (>85 years) and 42 patients without AS (9 patients <50 years, 20 patients between 51-70 years and 13 patients 70-85 years). When comparing patients 70-85 years, AA distensibility was significantly lower in those with AS compared to those without AS (0.9 ± 0.9 vs. 1.4 ± 1.1, P = 0.03) while there was no difference in the PDA (1.0 ± 1.1 vs. 1.0 ± 1.2, P = 0.26) and DDA (1.1 ± 1.2 vs. 1.2 ± 0.8, P = 0.97). In patients without AS, AD decreased with age in all aortic regions (P < 0.001). The AA in patients <50 years were the most distensible compared to other aortic regions. There is regional variation in aortic distensibility with aging. Patients with aortic stenosis demonstrated regional differences in aortic distensibility with lower distensibility demonstrated in the proximal ascending aorta compared to an age-matched cohort. PMID:25855464

  8. 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

  9. The Self-Expanding Symetis Acurate Does Not Increase Cerebral Microembolic Load When Compared to the Balloon-Expandable Edwards Sapien Prosthesis: A Transcranial Doppler Study in Patients Undergoing Transapical Aortic Valve Implantation

    PubMed Central

    Erdoes, Gabor; Huber, Christoph; Basciani, Reto; Stortecky, Stefan; Windecker, Stephan; Wenaweser, Peter; Carrel, Thierry; Eberle, Balthasar

    2014-01-01

    Objectives The aim of this study was to quantify potential differences in count, frequency and pattern of high-intensity transient signals (HITS) during transapical transcatheter aortic valve implantation (TA-TAVI), by comparing the Symetis Acurate TA (SA) with the balloon-expandable Edwards Sapien XT (ES) system. Background Recently, the Symetis Acurate TA revalving system has been introduced for TA-TAVI. The Symetis Acurate TA aortic bioprosthesis is self-expanding and is deployed by a specific two-step implantation technique. Whether this novel method increases the load of intraprocedural emboli, detected by transcranial Doppler ultrasound (TCD) as HITS, or not is not clear. Methods Twenty-two patients (n = 11 in each study arm, median logistic EuroScore 20%, median STS score 7%) displayed continuous TCD signals of good quality throughout the entire TA-TAVI procedure and were included in the final analysis. Data are presented as median with interquartile ranges. Results No significant differences were detected in total procedural or interval-related HITS load (SA: 303 [200; 594], ES: 499 [285; 941]; p = 0.16). With both devices, HITS peaked during prosthesis deployment (PD), whereas significantly fewer HITS occurred during instrumentation (SA: p = 0.002; ES: <0.001) or post-implantation PI (SA: p = 0.007; ES: <0.001). PD-associated HITS amounted to almost half of the total HITS load. One patient suffered new disabling stroke at 30 days. Thirty-day mortality amounted to 13.6% (3 of 22 patients). Conclusions Simplified transapical delivery using the self-expanding SA device does not increase HITS, despite of a two-step deployment technique with more interactions with the native aortic valve, when compared to the balloon-expandable ES valve. The similarity in HITS count, frequency and pattern with the two systems suggests a common mechanism for the release of cerebral microemboli. PMID:25289688

  10. 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

  11. 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

  12. 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

  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. 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.

  15. 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

  16. Cicletanine stimulates eNOS phosphorylation and NO production via Akt and MAP kinase/Erk signaling in sinusoidal endothelial cells.

    PubMed

    Liu, Songling; Rockey, Don C

    2013-07-15

    The function of the endothelial isoform of nitric oxide synthase (eNOS) and production of nitric oxide (NO) is altered in a number of disease states. Pharmacological approaches to enhancing NO synthesis and thus perhaps endothelial function could have substantial benefits in patients. We analyzed the effect of cicletanine, a synthetic pyridine with potent vasodilatory characteristics, on eNOS function and NO production in normal (liver) and injured rat sinusoidal endothelial cells, and we studied the effect of cicletanine-induced NO on stellate cell contraction and portal pressure in an in vivo model of liver injury. Sinusoidal endothelial cells were isolated from normal and injured rat livers. After exposure to cicletanine, eNOS phosphorylation, NO synthesis, and the signaling pathway regulating eNOS activation were measured. Cicletanine led to an increase in eNOS (Ser¹¹⁷⁷) phosphorylation, cytochrome c reductase activity, L-arginine conversion to L-citrulline, as well as NO production. The mechanism of the effect of cicletanine appeared to be via the protein kinase B (Akt) and MAP kinase/Erk signaling pathways. Additionally, cicletanine improved NO synthesis in injured sinusoidal endothelial cells. NO production induced by cicletanine in sinusoidal endothelial cells increased protein kinase G (PKG) activity as well as relaxation of stellate cells. Finally, administration of cicletanine to mice with portal hypertension induced by bile duct ligation led to reduction of portal pressure. The data indicate that cicletanine might improve eNOS activity in injured sinusoidal endothelial cells and likely activates hepatic stellate cell NO/PKG signaling. It raises the possibility that cicletanine could improve intrahepatic vascular function in portal hypertensive patients. PMID:23639812

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

    PubMed

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

    2016-08-01

    Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies. PMID:27277302

  18. Improvement of thoracic aortic vasoreactivity by continuous and intermittent exercise in high-fat diet-induced obese rats

    PubMed Central

    LIU, HONGPENG; YANG, ZHEN; HU, JIAN; LUO, YAN; ZHU, LINGQIN; YANG, HUIFANG; LI, GUANGHUA

    2015-01-01

    The aim of the present study was to explore the effects of continuous and intermittent exercise on the thoracic aortic vasoreactivity and free radical metabolism in rats fed with a high-fat diet (HD). Sprague-Dawley (SD) rats were randomly divided into four groups (n=8, each group): Conventional diet (CD), HD, HD with continuous exercise (HCE) and HD with intermittent exercise (HIE). HCE rats swam once/day for 90 min; HIE rats performed swimming exercises 3 times/day, 30 min each time with an interval of 4 h. In these two groups, the exercise was conducted 5 days a week for 8 weeks. Rats in the CD and HD groups were fed without swimming training. At the end of the exercise, all the rats were sacrificed and the blood, thoracic aorta and myocardium were collected immediately. The thoracic aortic vasoreactivity, the plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), malondialdehyde (MDA) and vascular endothelial nitric oxide synthase (eNOS) gene expression were measured. Compared to the control group, in the HD group the enhanced contractile response of the thoracic aortic rings to noradrenaline (NA) was observed (P<0.01). The levels of TC and LDL (P<0.01) were also increased in serum while the HDL level was reduced without statistical significance. In addition, the MDA content was upregulated in the myocardium, but the SOD level decreased (P<0.01). Furthermore, the expression of vascular eNOS mRNA was reduced (P<0.01). However, following the exercise the contraction of the thoracic aorta vascular rings to NA was reduced in the HCE and HIE groups (P<0.01), and the decreased contractile response was more evident in the HIE group compared to the HCE group (P<0.01). Additionally, in the HCE group the level of TG (P<0.01) was decreased, while the HDL (P<0.01) level was increased. Although the reduction of the TC and LDL level was also observed there was no significant difference

  19. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections

    PubMed Central

    Kuang, Shao-Qing; Medina-Martinez, Olga; Guo, Dong-chuan; Gong, Limin; Regalado, Ellen S.; Reynolds, Corey L.; Boileau, Catherine; Jondeau, Guillaume; Prakash, Siddharth K.; Kwartler, Callie S.; Zhu, Lawrence Yang; Peters, Andrew M.; Duan, Xue-Yan; Bamshad, Michael J.; Shendure, Jay; Nickerson, Debbie A.; Santos-Cortez, Regie L.; Dong, Xiurong; Leal, Suzanne M.; Majesky, Mark W.; Swindell, Eric C.; Jamrich, Milan; Milewicz, Dianna M.

    2016-01-01

    The ascending thoracic aorta is designed to withstand biomechanical forces from pulsatile blood. Thoracic aortic aneurysms and acute aortic dissections (TAADs) occur as a result of genetically triggered defects in aortic structure and a dysfunctional response to these forces. Here, we describe mutations in the forkhead transcription factor FOXE3 that predispose mutation-bearing individuals to TAAD. We performed exome sequencing of a large family with multiple members with TAADs and identified a rare variant in FOXE3 with an altered amino acid in the DNA-binding domain (p.Asp153His) that segregated with disease in this family. Additional pathogenic FOXE3 variants were identified in unrelated TAAD families. In mice, Foxe3 deficiency reduced smooth muscle cell (SMC) density and impaired SMC differentiation in the ascending aorta. Foxe3 expression was induced in aortic SMCs after transverse aortic constriction, and Foxe3 deficiency increased SMC apoptosis and ascending aortic rupture with increased aortic pressure. These phenotypes were rescued by inhibiting p53 activity, either by administration of a p53 inhibitor (pifithrin-α), or by crossing Foxe3–/– mice with p53–/– mice. Our data demonstrate that FOXE3 mutations lead to a reduced number of aortic SMCs during development and increased SMC apoptosis in the ascending aorta in response to increased biomechanical forces, thus defining an additional molecular pathway that leads to familial thoracic aortic disease. PMID:26854927

  20. Aortic Balloon Valvuloplasty Prior to Orthotopic Liver Transplantation: A Novel Approach to Aortic Stenosis and End-Stage Liver Disease

    PubMed Central

    Coverstone, Edward; Korenblat, Kevin; Crippin, Jeffrey S.; Chapman, William C.; Kates, Andrew M.; Zajarias, Alan

    2014-01-01

    The combination of severe aortic stenosis and end-stage liver disease increases the morbidity and mortality of surgical aortic valve replacement or orthotopic liver transplantation resulting in a prohibitive operative risk. We propose a staged approach of balloon aortic valvuloplasty prior to orthotopic liver transplantation as a bridge to definitive aortic valve replacement. Between 2010 and 2012, four patients with severe aortic stenosis and end-stage liver disease underwent staged balloon aortic valvuloplasty followed by orthotopic liver transplantation. All patients had been deemed to be inappropriate candidates for liver transplantation or aortic valve surgery due to their comorbidity. One patient died of complications from a perivalvular abscess. Three patients went on to successful graft implantation and function and surgical recovery. Two of the three patients proceeded to definitive surgical aortic valve replacement with the remainder currently undergoing evaluation. In this case series, we present a novel approach of balloon aortic valvuloplasty prior to liver transplantation as a potential bridge to definitive treatment of severe aortic stenosis in the end-stage liver patient. PMID:25431682

  1. 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…

  2. Juxtarenal aortic occlusion.

    PubMed Central

    Tapper, S S; Jenkins, J M; Edwards, W H; Mulherin, J L; Martin, R S; Edwards, W H

    1992-01-01

    The authors' experience with 113 aortic occlusions in 103 patients during a 26-year period (1965 to 1991) is reviewed. The authors found three distinct patterns of presentation: group I (n = 26) presented with acute aortic occlusion, group II (n = 66) presented with chronic aortic occlusion, and group III (n = 21) presented with complete occlusion of an aortic graft. Perioperative mortality rates were 31%, 9%, and 4.7% for each respective group and achieved statistical significance when comparing group I with group II (p = 0.009) and group I with group III (p = 0.015). Group I presented with profound metabolic insults due to acute ischemia and fared poorly. Group II presented with chronic claudication and did well long-term. Group III presented with acute ischemia but did well because of established collateral circulation. The treatment and expected outcome of aortic occlusion depends on the cause. PMID:1616381

  3. Mechanism of aortic root dilation and cardiovascular function in tetralogy of Fallot.

    PubMed

    Seki, Mitsuru; Kuwata, Seiko; Kurishima, Clara; Nakagawa, Ryo; Inuzuka, Ryo; Sugimoto, Masaya; Saiki, Hirofumi; Iwamoto, Yoichi; Ishido, Hirotaka; Masutani, Satoshi; Senzaki, Hideaki

    2016-05-01

    The aortic root dilation in tetralogy of Fallot (TOF) is a long-term clinical problem, because a severely dilated aorta can lead to aortic regurgitation, dissection, or rupture, which can be fatal, necessitating surgical intervention. The details of the mechanism of aortic root dilation, however, are unclear. We have shown that aortic stiffness is increased in patients with repaired TOF, and may mirror the histological abnormality of elastic fiber disruption and matrix expansion. This aortic stiffness is related closely to the aortic dilation, indicating that aortic stiffness may be a predictor of outcome of aortic dilation. Furthermore, the aortic volume overload is a very important determinant of aortic diameter in TOF patients before corrective surgery. In addition, a chromosomal abnormality and the transforming growth factor-β signaling pathway, a major contributor to aortic dilation in Marfan syndrome, also affect this mechanism. In this way, aortic dilation in TOF patients is suggested to be a multifactorial disorder. The aim of this review was therefore to clarify the mechanism of aortic dilation in TOF, focusing on recent research findings. Studies linking histopathology, mechanical properties, molecular/cellular physiology, and clinical manifestations of aortic dilation facilitate appropriate treatment intervention and improvement of long-term prognosis of TOF. PMID:26809655

  4. Simvastatin induces a central hypotensive effect via Ras-mediated signalling to cause eNOS up-regulation

    PubMed Central

    Cheng, Wen-Han; Ho, Wen-Yu; Chang, Chien-Feng; Lu, Pei-Jung; Cheng, Pei-Wen; Yeh, Tung-Chen; Hong, Ling-Zong; Sun, Gwo-Ching; Hsiao, Michael; Tseng, Ching-Jiunn

    2013-01-01

    BACKGROUND AND PURPOSE Clinical studies indicate that statins have a BP-lowering effect in hypercholesterolemic individuals with hypertension. Specifically, statins modulate BP through the up-regulation of endothelial NOS (eNOS) activation in the brain. However, the signalling mechanisms through which statins enhance eNOS activation remain unclear. Therefore, we examined the possible signalling pathways involved in statin-mediated BP regulation in the nucleus tractus solitarii (NTS). EXPERIMENTAL APPROACH To investigate the involvement of Ras and other signalling pathways in simvastatin-induced effects on BP, BP and renal sympathetic nerve activity (RSNA) were determined in spontaneously hypertensive rats (SHRs) before and after i.c.v. administration of simvastatin in the absence and presence of a Ras-specific inhibitor (farnesyl thiosalicylic acid, FTS), a geranylgeranyltransferase inhibitor (GGTI-2133), a PI3K inhibitor (LY294002) or a MAPK-ERK kinase (MEK) inhibitor (PD98059). KEY RESULTS FTS significantly attenuated the decrease in BP and increased NO evoked by simvastatin and reversed the decrease in basal RSNA induced by simvastatin. Immunoblotting and pharmacological studies showed that inhibition of Ras activity by FTS significantly abolished simvastatin-induced phosphorylation of ERK1/2, ribosomal protein S6 kinase (RSK), Akt and decreased eNOS phosphorylation. Likewise, administration of Akt and ERK1/2 signalling inhibitors, LY294002 and PD98059, attenuated the reduction in BP evoked by simvastatin. Furthermore, i.c.v. simvastatin decreased Rac1 activation and the number of ROS-positive cells in the NTS. CONCLUSIONS AND IMPLICATIONS Simvastatin modulates central BP control in the NTS of SHRs by increasing Ras-mediated activation of the PI3K-Akt and ERK1/2-RSK signalling pathways, which then up-regulates eNOS activation. PMID:23889671

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

    PubMed

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

    2016-01-01

    Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1. PMID:26386740

  6. 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. PMID:25916721

  7. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.

    PubMed

    Boeldt, D S; Yi, F X; Bird, I M

    2011-09-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](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 [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, 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 [Ca(2+)](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

  8. [Use of sutureless prosthetic aortic valves in cardiac surgery].

    PubMed

    Santarpino, Giuseppe; Fischlein, Theodor

    2014-03-01

    In the last years, an increasing proportion of high-risk patients undergo surgical aortic valve replacement. In order to reduce the risk associated with cross-clamp time or cardioplegic ischemic time, sutureless aortic prostheses have been developed. These bioprosthetic valves are not hand sewn, and this technological advance translates into reduced implantation times, thus improving outcome of patients referred for aortic valve replacement. At present, three sutureless bioprostheses are available on the market: 3f Enable (Medtronic Inc., Minneapolis, Minnesota, USA), Perceval (Sorin Group, Saluggia, Italy) and Intuity (Edwards Lifesciences, Irvine, California, USA). This article provides an overview of the available literature on sutureless aortic valves with the aim to better define current role and future perspectives of sutureless aortic bioprostheses for the treatment of aortic valve stenosis. PMID:24770430

  9. 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

  10. Heat shock protein 90 and tyrosine kinase regulate eNOS NO* generation but not NO* bioactivity.

    PubMed

    Ou, Jingsong; Fontana, Jason T; Ou, Zhijun; Jones, Deron W; Ackerman, Allan W; Oldham, Keith T; Yu, Jun; Sessa, William C; Pritchard, Kirkwood A

    2004-02-01

    An increase in the association of heat shock protein 90 (HSP90) with endothelial nitric oxide (NO) synthase (eNOS) is well recognized for increasing NO (NO*) production. Despite the progress in this field, the mechanisms by which HSP90 modulates eNOS remain unclear due, in part, to the fact that geldanamycin (GA) redox cycles to generate superoxide anion (O(2)(-*) and the fact that inhibiting HSP90 with GA or radicicol (RAD) destabilizes tyrosine kinases that rely on the chaperone for maturation. In this report, we determine the extent to which these side effects alter vascular and endothelial cell function in physiologically relevant systems and in cultured endothelial cells. Vascular endothelial growth factor (VEGF)-stimulated vascular permeability, as measured by Evans blue leakage in the ears of male Swiss mice in vivo, and acetylcholine-induced vasodilation of isolated, pressurized mandibular arterioles from male C57BL6 mice ex vivo were attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME), GA, and RAD. Z-1[N-(2-aminoethyl)-N-(2-ammonoethyl)amino]diazen-1-ium-1,2-dioate (DETA-NONOate), a slow releasing NO. donor, increased vasodilation of arterioles pretreated with GA, RAD, and L-NAME equally well except at 10(-5) M, the highest concentration used, where vasodilation was greater in pressurized arterioles treated with L-NAME than in arterioles pretreated with GA or RAD alone. Both GA and RAD reduced NO* release from stimulated endothelial cell cultures and increased O(2)(-*) production in the endothelium of isolated aortas by an L-NAME-inhibitable mechanism. Pretreatment with RAD increased stimulated O(2)(-*) production from eNOS, whereas pretreatment with genistein (GE), a broad-spectrum tyrosine kinase inhibitor, did not; however, pretreatment with GE + RAD resulted in a super-induced state of uncoupled eNOS activity upon stimulation. These data suggest that the tyrosine kinases, either directly or indirectly, and HSP90-dependent signaling pathways

  11. 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

  12. Sexual dimorphism in rat aortic endothelial function of streptozotocin-induced diabetes: possible involvement of superoxide and nitric oxide production

    PubMed Central

    Han, Xiaoyuan; Zhang, Rui; Anderson, Leigh; Rahimian, Roshanak

    2013-01-01

    Little is known of the interactions between diabetes and sex on vascular function. The objectives of this study were to investigate whether there were sex differences in rat aortic endothelial function one week after the induction of streptozotocin (STZ)-diabetes, and to examine the potential roles of superoxide and nitric oxide (NO) in this sex-specific effect. Endothelium-dependent vasodilatation to acetylcholine (ACh) was measured in rat aortic rings before and after treatment with MnTMPyP (25 μM), a superoxide dismutase. Contractile responses to phenylephrine (PE) were generated before and after treatment with L-NAME (200 μM), a nitric oxide synthase (NOS) inhibitor. The mRNA expression of NADPH oxidase (Nox) and endothelial nitric oxide synthase (eNOS) were also determined. We demonstrated that 1) STZ-diabetes impaired endothelium-dependent vasodilatation to ACh to a greater extent in female than male aortae, 2) inhibition of superoxide enhanced sensitivity to ACh only in diabetic females, and 3) Nox1 and Nox4 mRNA expression was significantly elevated only in aortic tissue of diabetic females. Furthermore, incubation of aortic rings with L-NAME potentiated PE responses in all groups, but aortae from control females showed a greater potentiation of the PE response after NOS inhibition compared with others. STZ-diabetes reduced the extent of PE potentiation after L-NAME and the aortic eNOS mRNA expression in females to the same levels as seen in males. These data suggest that a decrease in NO, resulting from either decreased eNOS or elevated superoxide, may partially contribute to the predisposition of the female aorta to injury early in diabetes. PMID:24211329

  13. 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

  14. 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

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

    PubMed

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

    2014-09-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID:25015964

  16. 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

  17. 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

  18. 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

  19. 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

  20. Aortic valve surgery - open

    MedlinePlus

    ... choose to have your aortic valve surgery at a center that does many of these procedures. ... DA, Harken AH. Acquired heart disease: valvular. In: Townsend CM, ... Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: ...

  1. Double aortic arch

    MedlinePlus

    ... double aortic arch may press on the windpipe (trachea) and esophagus, leading to trouble breathing and swallowing. ... to relieve pressure on the esophagus and windpipe (trachea). The surgeon ties off the smaller branch and ...

  2. [Acute aortic syndrome].

    PubMed

    Nienaber, Christoph A

    2016-06-01

    Acute aortic syndrome is the common denominator for acute events to the aortic wall and encompasses dissection of the aorta, intramural hematoma, formation of aortic ulcers and trauma to the aorta with an annual incidence of up to 35 cases/100.000 between 65 and 75 years of age. Both, inflammation and/or microtrauma at the level of the aortic media layer, and a genetic disposition are promoting elements of AAS, while the extent and anatomic involvement of the ascending aorta call for either surgical resection/repair in the proximal part of the aorta, or an endovascular solution for pathologies in the distal aorta; in all cases of dissection (regardless of location) reconstruction/realignment has been proven to portend better long-term outcomes (in addition to medical management of blood pressure). PMID:27254622

  3. Abdominal aortic aneurysm

    MedlinePlus

    ... main blood vessel that supplies blood to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs ... dissection). Symptoms of rupture include: Pain in the abdomen or back. The pain may be severe, sudden, ...

  4. Abdominal aortic aneurysm.

    PubMed

    Setacci, Francesco; Galzerano, Giuseppe; De Donato, Gianmarco; Benevento, Domenico; Guerrieri, Massimiliano W; Ruzzi, Umberto; Borrelli, Maria P; Setacci, Carlo

    2016-02-01

    Endovascular repair of abdominal aortic aneurysms has become a milestone in the treatment of patients with abdominal aortic aneurysm. Technological improvement allows treatment in more and more complex cases. This review summarizes all grafts available on the market. A complete review of most important trial on this topic is provided to the best of our knowledge, and technical tips and tricks for standard cases are also included. PMID:26771730

  5. 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

  6. Nitric oxide stimulates matrix synthesis and deposition by adult human aortic smooth muscle cells within three-dimensional cocultures.

    PubMed

    Simmers, Phillip; Gishto, Arsela; Vyavahare, Narendra; Kothapalli, Chandrasekhar R

    2015-04-01

    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 and SMC

  7. 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

  8. Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium.

    PubMed

    Feng, Zhe; Wei, Ri-Bao; Hong, Quan; Cui, Shao-Yuan; Chen, Xiang-Mei

    2010-10-01

    GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H2O2 (hydrogen peroxide)-treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H2O2-treated cells in a dose-dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose-dependent manner in H2O2-treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 microM GSE, 2.0 microM TG (thapsigargin) and 20.0 microM 2-APB (2-aminoethoxydiphenyl borate) instead of 0.25 microM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p-AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up-regulation of eNOS and NO expression via inhibiting InsP3Rs (inositol 1,4,5-trisphosphate receptors)-mediated intracellular excessive calcium release and by activating p-AKT in endothelial cells. PMID:20513234

  9. Transcatheter aortic valve insertion (TAVI): a review

    PubMed Central

    Morgan-Hughes, G; Roobottom, C

    2014-01-01

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

  10. 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

  11. Aortic aneurysm repair - endovascular- discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000236.htm Aortic aneurysm repair - endovascular - discharge To use the sharing features ... enable JavaScript. AAA repair - endovascular - discharge; Repair - aortic aneurysm - endovascular - discharge; EVAR - discharge; Endovascular aneurysm repair - discharge ...

  12. 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 ...

  13. 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.

  14. 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

  15. Antenatal Maternally-Administered Phosphodiesterase Type 5 Inhibitors Normalize eNOS Expression in the Fetal Lamb Model of Congenital Diaphragmatic Hernia

    PubMed Central

    Shue, Eveline H; Schecter, Samuel C.; Gong, Wenhui; Etemadi, Mozziyar; Johengen, Michael; Iqbal, Corey; Derderian, S. Christopher; Oishi, Peter; Fineman, Jeffrey R.; Miniati, Doug

    2013-01-01

    Purpose Pulmonary hypertension (pHTN), a main determinant of survival in congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling. Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to treat pHTN. The purpose of this study is to determine if antenatal PDE5 inhibitors can prevent pHTN in the fetal lamb model of CDH. Methods CDH were created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or tadalafil, a PDE5 inhibitor, until delivery. Near term gestation, lambs underwent resuscitations, and lung tissue was snap frozen for protein analysis. Results Mean cGMP levels were 0.53±0.11 in placebo-treated fetal lambs and 1.73±0.21 in tadalafil-treated fetal lambs (p=0.002). Normalized expression of eNOS was 82±12% in Normal-Placebo, 61±5% in CDH-Placebo, 116±6% in Normal-Tadalafil, and 86±8% in CDH-Tadalafil lambs. Normalized expression of β-sGC was 105±15% in Normal-Placebo, 82±3% in CDH-Placebo, 158±16% in Normal-Tadalafil, and 86±8% in CDH-Tadalafil lambs. Endothelial NOS and β-sGC were significantly decreased in CDH (p = 0.0007 and 0.01 for eNOS and β-sGC, respectively), and tadalafil significantly increased eNOS expression (p = 0.0002). Conclusions PDE5 inhibitors can cross the placental barrier. β-sGC and eNOS are downregulated in fetal lambs with CDH. Antenatal PDE5 inhibitors normalize eNOS and may prevent in utero vascular remodeling in CDH. PMID:24439578

  16. 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

  17. [Abdominal aortic aneurysm and renovascular disease].

    PubMed

    Riambau, Vicente; Guerrero, Francisco; Montañá, Xavier; Gilabert, Rosa

    2007-06-01

    Recent technological advances in the diagnosis and therapy of abdominal aortic aneurysm and renovascular disease are continuing to bring about changes in the way patients suffering from these conditions are treated. The prevalence of both these conditions is increasing. This is due to greater life-expectancy in patients with arteriosclerosis, a pathogenetic factor underlying both conditions. The application of diagnostic imaging techniques to non-vascular conditions has led to the early diagnosis of abdominal aortic aneurysm. Clinical suspicion of reno-vascular disease can be confirmed easily using high-resolution diagnostic imaging modalities such as CT angiography and magnetic resonance angiography. Endovascular intervention is successfully replacing conventional surgical repair techniques, with the result that it may be possible to improve outcome in both conditions using effective and minimally invasive approaches. Future technological developments will enable these endovascular techniques to be applied in the large majority of patients with abdominal aortic aneurysm or renovascular disease. PMID:17580053

  18. 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. PMID:27089822

  19. 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. PMID:27021619

  20. [The different genotypes of MTHFR 1298A>C and PON1 -108C>T polymorphisms confer the increased risk of the abdominal aortic aneurysm in the smoking and nonsmoking persons].

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2005-01-01

    In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered

  1. 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

  2. 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

  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. 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

  5. The Contribution of Enos Nuttall to the Development of Education in Jamaica.

    ERIC Educational Resources Information Center

    Allen, Beryl M.

    1984-01-01

    Describes Enos Nuttall's contribution to educational thought and practice in Jamaica. His beliefs on education for all (but differentiated according to individual needs and capabilities) are discussed, as well as his influence on educational reform and curriculum development. (SK)

  6. Bicuspid aortic valve

    MedlinePlus

    ... is unclear, but it is the most common congenital heart disease . It often runs in families. The bicuspid aortic ... A.M. Editorial team. Related MedlinePlus Health Topics Congenital Heart Defects Heart Valve Diseases Browse the Encyclopedia A.D.A.M., Inc. ...

  7. New-onset atrial fibrillation after surgical aortic valve replacement and transcatheter aortic valve implantation: a concise review.

    PubMed

    Jørgensen, Troels Højsgaard; Thygesen, Julie Bjerre; Thyregod, Hans Gustav; Svendsen, Jesper Hastrup; Søndergaard, Lars

    2015-01-01

    Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic valve implantation (TAVI) have been shown to be the only treatments that can improve the natural cause of severe aortic valve stenosis. However, after SAVR and TAVI, the incidence of new-onset atrial fibrillation (NOAF) is 31%-64% and 4%-32%, respectively. NOAF is independently associated with adverse events such as stroke, death, and increased length of hospital stay. Increasing the knowledge of predisposing factors, optimal postprocedural monitoring, and prophylactic antiarrhythmic and antithrombotic therapy may reduce the risk of complications secondary to NOAF. PMID:25589700

  8. 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

  9. Upregulation of ERK1/2-eNOS via AT2 receptors decreases the contractile response to angiotensin II in resistance mesenteric arteries from obese rats.

    PubMed

    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. Aortic valve annuloplasty: new single suture technique.

    PubMed

    Schöllhorn, Joachim; Rylski, Bartosz; Beyersdorf, Friedhelm

    2014-06-01

    Reconstruction strategies for aortic valve insufficiency in the presence of aortic annulus dilatation are usually surgically challenging. We demonstrate a simple, modified Taylor technique of downsizing and stabilization of the aortic annulus using a single internal base suture. Since April 2011, 22 consecutive patients have undergone safe aortic valve annuloplasty. No reoperations for aortic valve insufficiency and no deaths occurred. PMID:24882316

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

    PubMed

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

    2008-01-01

    Intra-aortic balloon pumping (IABP) could modify the arterial biomechanics; however, its effects on arterial wall properties have not been fully explored. This dynamical study was designed to characterize the pressure-dependent and smooth muscle-dependent effects of IABP on aortic wall energetics in an in vivo animal model. Intra-aortic balloon pumping (1:2) was performed in six anesthetized sheep in which aortic pressure and diameter signals were measured in basal, augmented (during balloon inflation), and assisted (postaugmented) beats. Energy dissipation values in augmented and assisted beats were significantly higher than those observed in basal state (p < 0.05). Assisted beats showed a significant increase of wall damping with respect to basal and augmented beats (p < 0.05). Intra-aortic balloon pumping resulted in a significant increase of pulse wave velocity (p < 0.05) in augmented beats with respect to basal state (6.3 +/- 0.8 vs. 5.2 +/- 0.5 m x s(-1)); whereas values observed in assisted beats were significantly (p < 0.05) lower than those observed in augmented beats (4.9 +/- 0.5 vs. 6.3 +/- 0.8 m x s(-1)). Our findings show that IABP determined the pressure and smooth muscle-dependent changes in arterial wall energetics and damping properties in this animal model. PMID:18204315

  12. 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

  13. Transcatheter Aortic Valve Implantation in the Elderly: Who to Refer?

    PubMed Central

    Finn, Matthew; Green, Philip

    2015-01-01

    In recent years, experience with transcatheter aortic valve implantation has led to improved outcomes in elderly patients with severe aortic stenosis (AS) who may not have previously been considered for intervention. These patients are often frail with significant comorbid conditions. As the prevalence of AS increases, there is a need for improved assessment parameters to determine the patients most likely to benefit from this novel procedure. This review discusses the diagnostic criteria for severe AS and the trials available to aid in the decision to refer for aortic valve procedures in the elderly. PMID:25216621

  14. A new technique to explant an infected aortic endograft.

    PubMed

    Popplewell, Matthew A; Garnham, Andrew W; Hobbs, Simon D

    2015-08-01

    The management of an infected aortic endograft can be challenging both operatively and clinically. Although aortic endograft infection is rare, the incidence is likely to increase in the coming years because of ever rising numbers of endovascular aneurysm repairs. Definitive management involves the removal of the endograft through laparotomy. Removal of the graft is technically challenging; no manufacturer's device is available to assist in disengagement of barbed hooks that hold the endograft in position. We present a new technique using the disposable proctoscope as a device to facilitate safe removal of the endograft with minimal damage to the aortic wall. PMID:25937607

  15. Extensive spinal epidural hematoma: a rare complication of aortic coarctation.

    PubMed

    Zizka, J; Eliás, P; Michl, A; Harrer, J; Cesák, T; Herman, A

    2001-01-01

    Development of collateral circulation belongs among the typical signs of aortic coarctation. Cerebral or spinal artery aneurysm formation with increased risk of subarachnoid hemorrhage represent the most common neurovascular complication of this disease. We report a case of a 20-year-old sportsman who developed acute non-traumatic paraplegia as a result of extensive spinal epidural hemorrhage from collateral vessels accompanying aortic coarctation which was unrecognized up to that time. To the best of our knowledge, acute spinal epidural hematoma as a complication of aortic coarctation has not been previously reported. PMID:11471620

  16. Using The Descending Aortic Wall Thickness Measured In Transesophageal Echocardiography As A Risk Marker For Aortic Dissection

    PubMed Central

    Fanari, Zaher; Hammami, Sumaya; Hammami, Muhammad Baraa; Hammami, Safa; Eze-Nliam, Chete; Weintraub, William S.

    2015-01-01

    Objective The aim of this study is to estimate whether aortic wall thickness is increased in patients with Aortic dissection (AD) compared to low risk control group and can be used in addition to aortic diameter as a risk marker of AD. Background AD occurs due to pathologies that may increase thickness of the aortic wall. Transesophageal echocardiography (TEE) has the ability to visualize both the thoracic aortic wall and lumen. Aortic diameter has been used to predict aortic dissection and timing of surgery, but it is not always predictive of that risk. Methods In 48 patients with AD who underwent TEE were examined retrospectively and compared to 48 control patients with patent foramen ovale (PFO). We measured aortic diameter at different levels, intimal/medial thickness (IMT) and complete wall thickness (CMT). Demographic data and cardiovascular risk factors were reviewed. The data was analyzed using ANOVA and student t test. Results (AD) patients were older [mean age 66 AD vs. 51 PFO], had more hypertension, diabetes, hyperlipidemia and Coronary artery disease. Both IMT and CMT in the descending aorta were increased in AD group [(1.85 vs. 1.43 mm; P=0.03 and 2.93 vs. 2.46 mm; p=0.01). As expected the diameter of ascending aorta was also greater in AD (4.61 vs. 2.92 cm; P=0.004). Conclusions CMT and IMT in the descending aorta detected by TEE is greater in patients with AD when compared to control and may add prognostic data to that of aortic diameter. PMID:25984293

  17. 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

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

    PubMed Central

    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

  19. Enlargement of the aortic annulus during aortic valve replacement: a review.

    PubMed

    Bortolotti, Uberto; Celiento, Michele; Milano, Aldo D

    2014-01-01

    The main goal of aortic valve replacement (AVR) is to obtain relief from the fixed left ventricular (LV) obstruction by replacing the aortic valve with a prosthesis, either mechanical or biological, of adequate size. Most currently available prostheses provide satisfactory hemodynamic performance, but small-sized prostheses may be associated with high transvalvular gradients and suboptimal effective orifice area that result in prosthesis-patient mismatch (PPM), and thus are far from ideal for use in young, active patients. The avoidance of PPM is advisable as it has been repeatedly associated with increased mortality, decreased exercise tolerance and an impaired regression of LV hypertrophy after AVR for severe aortic stenosis. Enlargement of the aortic annulus (EAA) has proved to be a valuable method to prevent PPM in the presence of a diminutive aortic root. This review outlines the various techniques described for EAA, presenting technical details, long-term results and major procedure-related complications, and discussing the current role of EAA in patients requiring AVR. PMID:24779326

  20. 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

  1. 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

    Alhosin, Mahmoud; Anselm, Eric; Rashid, Sherzad; Kim, Jong Hun; Madeira, Socorro Vanesca Frota; 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

  2. 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

  3. [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

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

    PubMed

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

    2016-05-01

    Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients. PMID:26129868

  5. Thrombocytosis following splenectomy and aortic valve replacement for idiopathic thrombocytopaenic purpura with bicuspid aortic valve

    PubMed Central

    Katiyar, Sarika; Ganjsinghani, Payal Kamlesh; Jain, Rajnish Kumar

    2015-01-01

    Idiopathic thrombocytopaenic purpura (ITP) patients are at high risk for complications during and after cardiac surgeries involving cardiopulmonary bypass. The main clinical problem of primary ITP is an increased risk of bleeding although bleeding may not always be present. More recently, thrombosis has become appreciated as another potential complication of the procedure. We report a 22-year-old female patient with ITP with bicuspid aortic valve and splenomegaly, who underwent uncomplicated aortic valve replacement and splenectomy simultaneously. She was readmitted with chest pain due to coronary thrombosis following splenectomy which made the management difficult. We describe our experience in managing this patient who presented with thrombotic complication rather than bleeding in post-operative period and the challenges met in maintaining appropriate anticoagulation for aortic valve replacement as well as thrombosis, post-splenectomy PMID:26379295

  6. 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.

  7. 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

  8. 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.

  9. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Rifaai, Rehab A.; Hassan, Magdy K.

    2014-01-01

    Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production. PMID:25120567

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

    PubMed Central

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

    2014-01-01

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

  11. Cilostazol Induces PGI2 Production via Activation of the Downstream Epac-1/Rap1 Signaling Cascade to Increase Intracellular Calcium by PLCε and to Activate p44/42 MAPK in Human Aortic Endothelial Cells

    PubMed Central

    Hashimoto, Ayako

    2015-01-01

    Background Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, is known as an anti-platelet drug and acts directly on platelets. Cilostazol has been shown to exhibit vascular protection in ischemic diseases. Although vascular endothelium-derived prostaglandin I2 (PGI2) plays an important role in vascular protection, it is unknown whether cilostazol directly stimulates PGI2 synthesis in endothelial cells. Here, we elucidate the mechanism of cilostazol-induced PGI2 stimulation in endothelial cells. Methods and Results Human aortic endothelial cells (HAECs) were stimulated with cilostazol and PGI2 accumulation in the culture media was measured. Cilostazol increased PGI2 synthesis via the arachidonic acid pathway. Cilostazol-induced intracellular calcium also promoted PGI2 synthesis via the inositol 1,4,5-trisphosphate receptor. Using RNAi, silencing of PDE3B abolished the induction effect of cilostazol on PGI2 synthesis and intracellular cAMP accumulation. Inhibition of the exchange protein, which was directly activated by cyclic AMP 1 (Epac-1) and its downstream signal the Ras-like small GTPase (Rap-1), abolished cilostazol-induced PGI2 synthesis, but this did not take place via protein kinase A (PKA). Inhibition of downstream signaling, such as mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) γ, and phospholipase C (PLC) ε, suppressed cilostazol-induced PGI2 synthesis. Conclusions The PDE3/Epac-1/Rap-1 signaling pathway plays an important role in cilostazol-induced PGI2 synthesis. Namely, stimulation of HAECs with cilostazol induces intracellular calcium elevation via the Rap-1/PLCε/IP3 pathway, along with MAPK activation via direct activation by Epac-1/Rap-1 and indirect activation by Epac-1/Rap-1/PI3Kγ, resulting in synergistically induced PGI2 synthesis. PMID:26181635

  12. 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

  13. 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

  14. 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

  15. 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

  16. Extensive Ethnogenomic Diversity of Endothelial Nitric Oxide Synthase (eNOS) Polymorphisms

    PubMed Central

    Thomas, Bolaji N.; Thakur, Tanya J.; Yi, Li; Guindo, Aldiouma; Diallo, Dapa A.; Ott, Jurg

    2013-01-01

    Nitric oxide (NO) is highly reactive, produced in endothelial cells by endothelial NO synthase (eNOS) and has been implicated in sickle cell pathophysiology. We evaluated the distribution of functionally significant eNOS variants (the T786C variant in the promoter region, the Glu298Asp variant in exon 7, and the variable number of tandem repeats (VNTR) in intron 4) in Africans, African Americans and Caucasians. The C-786 variant was more common in Caucasians than in Africans and African Americans. Consistent with other findings, the Asp-298 variant had the highest frequency in Caucasians followed by African Americans, but was completely absent in Africans. The very rare intron 4 allele, eNOS 4c, was found in some Africans and African Americans, but not in Caucasians. eNOS 4d allele was present in 2 Africans. These findings suggest a consistent and widespread genomic diversity in the distribution of eNOS variants in Africans, comparative to African Americans and Caucasians. PMID:23400313

  17. Extensive ethnogenomic diversity of endothelial nitric oxide synthase (eNOS) polymorphisms.

    PubMed

    Thomas, Bolaji N; Thakur, Tanya J; Yi, Li; Guindo, Aldiouma; Diallo, Dapa A; Ott, Jurg

    2013-01-01

    Nitric oxide (NO) is highly reactive, produced in endothelial cells by endothelial NO synthase (eNOS) and has been implicated in sickle cell pathophysiology. We evaluated the distribution of functionally significant eNOS variants (the T786C variant in the promoter region, the Glu298Asp variant in exon 7, and the variable number of tandem repeats (VNTR) in intron 4) in Africans, African Americans and Caucasians. The C-786 variant was more common in Caucasians than in Africans and African Americans. Consistent with other findings, the Asp-298 variant had the highest frequency in Caucasians followed by African Americans, but was completely absent in Africans. The very rare intron 4 allele, eNOS 4c, was found in some Africans and African Americans, but not in Caucasians. eNOS 4d allele was present in 2 Africans. These findings suggest a consistent and widespread genomic diversity in the distribution of eNOS variants in Africans, comparative to African Americans and Caucasians. PMID:23400313

  18. 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

  19. 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

  20. 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

  1. 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. PMID:27127562

  2. Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

    PubMed Central

    Viboolvorakul, Sheepsumon; Patumraj, Suthiluk

    2014-01-01

    This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, n = 5), sedentary aged (SE-Aged, n = 8), immersed-aged (IM-Aged, n = 5), and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, n = 8) rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF) in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (P < 0.05). Moreover, the percentage of capillary vascularity (%CV) and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (P < 0.05). These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS. PMID:24822184

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

    PubMed Central

    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

  4. Postpartum patient with thrombosis of mechanical prostheses and acquired supravalvular aortic stenosis.

    PubMed

    Benfatti, Ricardo Adala; Martins Júnior, Carlos Roberto; Silva, Guilherme Viotto Rodrigues da; Pontes, José Carlos Dorsa Vieira

    2011-01-01

    The blood hypercoagulability in pregnancy increases significantly the incidence of thrombosis of mechanical valves. Acquired supravalvular aortic stenosis is extremely rare. We report the case of an immediate postpartum patient with aortic mechanical prostheses and acquired supravalvular aortic stenosis who underwent emergency heart surgery, with severe hemodynamic instability, using adapted surgical technique for correction of supravalvular stenosis with satisfactory clinical and echocardiography results. PMID:21894422

  5. New St. Jude Medical Portico™ transcatheter aortic valve: features and early results.

    PubMed

    Spence, M S; Lyons, K; McVerry, F; Smith, B; Manoharan, G B; Maguire, C; Doherty, R; Anderson, L; Morton, A; Hughes, S; Hoeritzauer, I; Manoharan, G

    2013-06-01

    Patients with symptomatic aortic valve disease who are inoperable or have high surgery-related risks may be treated with transcatheter aortic valve implantation devices. With this method increasingly applied, device innovations are aimed at achieving improved procedural results and therapeutic outcome. This paper describes the innovations implemented in the St. Jude Medical Portico™ system for transcatheter aortic valve implantation, the application of this system and initial clinical experience. PMID:23681129

  6. 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.

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

    PubMed Central

    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

  8. 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

  9. 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

  10. 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

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  12. Sex Differences in Aortic Stenosis and Outcome Following Surgical and Transcatheter Aortic Valve Replacement.

    PubMed

    Dobson, Laura E; Fairbairn, Timothy A; Plein, Sven; Greenwood, John P

    2015-12-01

    Aortic stenosis is the commonest valve defect in the developed world and is associated with a high mortality once symptomatic. There is a difference in the way that male and female hearts remodel in the face of chronic pressure overload: women develop a concentrically hypertrophied, small cavity left ventricle (LV), whereas men are more prone to the development of eccentric hypertrophy. At a cellular level, there is an increase in collagen and metalloproteinase gene expression in males suggesting a different regulation of extracellular volume composition according to sex. Male hearts with aortic stenosis appear to have more fibrosis than their female comparators. The trigger for this appears to be in part related to estrogen receptor signaling, but other factors such as renin-angiotensin activation, nitric oxide, and circulating noradrenaline levels may also be implicated. Treatment options include surgical valve replacement (SAVR) and more recently transcatheter aortic valve replacement (TAVR). Female sex may be a risk factor for adverse outcome following SAVR and conversely appears to confer a survival advantage when undergoing TAVR. Whether the lower mortality seen following TAVR in women compared with men (despite their increased age and frailty) reflects their longer life expectancy, smaller annular size (and less post-TAVR aortic regurgitation), more favorable LV reverse remodeling, or more likely, a combination of these factors remains to be established. PMID:26653869

  13. CT of acute abdominal aortic disorders.

    PubMed

    Bhalla, Sanjeev; Menias, Christine O; Heiken, Jay P

    2003-11-01

    Aortic aneurysm rupture, aortic dissection, PAU, acute aortic occlusion, traumatic aortic injury, and aortic fistula represent acute abdominal aortic conditions. Because of its speed and proximity to the emergency department, helical CT is the imaging test of choice for these conditions. MR imaging also plays an important role in the imaging of aortic dissection and PAU, particularly when the patient is unable to receive intravenous contrast material. In this era of MDCT, conventional angiography is used as a secondary diagnostic tool to clarify equivocal findings on cross-sectional imaging. Ultrasound is helpful when CT is not readily available and the patient is unable or too unstable to undergo MR imaging. PMID:14661663

  14. 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

  15. 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.

  16. Update in the management of type B aortic dissection.

    PubMed

    Nauta, Foeke Jh; Trimarchi, Santi; Kamman, Arnoud V; Moll, Frans L; van Herwaarden, Joost A; Patel, Himanshu J; Figueroa, C Alberto; Eagle, Kim A; Froehlich, James B

    2016-06-01

    Stanford type B aortic dissection (TBAD) is a life-threatening aortic disease. The initial management goal is to prevent aortic rupture, propagation of the dissection, and symptoms by reducing the heart rate and blood pressure. Uncomplicated TBAD patients require prompt medical management to prevent aortic dilatation or rupture during subsequent follow-up. Complicated TBAD patients require immediate invasive management to prevent death or injury caused by rupture or malperfusion. Recent developments in diagnosis and management have reduced mortality related to TBAD considerably. In particular, the introduction of thoracic stent-grafts has shifted the management from surgical to endovascular repair, contributing to a fourfold increase in early survival in complicated TBAD. Furthermore, endovascular repair is now considered in some uncomplicated TBAD patients in addition to optimal medical therapy. For more challenging aortic dissection patients with involvement of the aortic arch, hybrid approaches, combining open and endovascular repair, have had promising results. Regardless of the chosen management strategy, strict antihypertensive control should be administered to all TBAD patients in addition to close imaging surveillance. Future developments in stent-graft design, medical therapy, surgical and hybrid techniques, imaging, and genetic screening may improve the outcomes of TBAD patients even further. We present a comprehensive review of the recommended management strategy based on current evidence in the literature. PMID:27067136

  17. Unusual Case of Overt Aortic Dissection Mimicking Aortic Intramural Hematoma

    PubMed Central

    Disha, Kushtrim; Kuntze, Thomas; Girdauskas, Evaldas

    2016-01-01

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

  18. 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

  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

    Matalanis, George; Perera, Nisal K; Galvin, Sean D

    2016-05-01

    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. 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

  4. 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

  5. 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...

  6. 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...

  7. 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

  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. Deformation of Congenital Bicuspid Aortic Valves in Systole

    NASA Astrophysics Data System (ADS)

    Szeto, Kai; Pastuszko, Peter; Nigam, Vishal; Lasheras, Juan

    2012-11-01

    Clinical studies have shown that patients with congenital bicuspid aortic valves (CBAVs) develop degenerative calcification of the leaflets at young ages compared to normal tricuspid aortic valves (TAVs). It has been hypothesized that the asymmetrical geometry of the leaflets in CBAVs and the associate changes in flow shear stresses and excessive strain rate levels are possible causes for the early calcification. Central to the validation of this hypothesis is the need to quantify the differences in strain rate levels between the BAVs and TAVs. We simulate the CBAVs by surgically stitching two of the leaflets of a porcine aortic valve together. To quantify strain differences, we performed in-vitro experiments in both BAVs and TAVs by tracking the 3-D motion of small dots marked on each leaflet surface. We then used phase-locked stereo photogrammetry to measure the strain rates in both radial and circumferential directions during the whole cardiac cycle. In the BAVs' case, the fused leaflet experiences an almost 30% increase in the radial stretching when fully open. RNA profiling of human aortic valve interstitial cells exposed to cyclic stretch shows that the increased stretch experienced by the BAVs results in increased levels of INTERLEUKINS (ILs) and other known inflammatory markers associated with aortic valve calcification. Together, these observations suggest that the abnormal stretch experienced by BAVs activates inflammation gene expression.

  10. Chronic type B aortic dissection: indications and strategies for treatment.

    PubMed

    Rohlffs, F; Tsilimparis, N; Diener, H; Larena-Avellaneda, A; Von Kodolitsch, Y; Wipper, S; Debus, E S; Kölbel, T

    2015-04-01

    Chronic type B aortic dissection is a distinctive condition that needs individual treatment strategies and different considerations than in therapy of acute or subacute type B aortic dissection. The most common indication for treatment of this complex disease is aneurysmal dilatation of the dissected aortic segment. While open repair of the enlarged dissected aorta remains the best option for good-risk patients and patients with connective tissue disorders in high-volume centers with respective expertise, endovascular management of chronic type B aortic dissection with postdissection aneurysms has significantly gained ground in the past years. But the concept of TEVAR with implantation of a tubular stent-graft into the thoracic aorta to seal the proximal entry tear and reroute the blood flow into the true lumen alone, is not associated with satisfactory results. This is mainly due to the sparse remodeling capacity of the aortic tissue compared to earlier stages of the disease as the aortic wall and the dissection membrane are thickened and more rigid. On the other hand, it is restricted by the most limiting factor for endovascular success in chronic type B aortic dissection: persistent false lumen perfusion. This problem also affects patients with residual dissection after surgical repair of a DeBakey type I aortic dissection or dissection after ascending aortic repair for other pathologies. Hence, it is evident that strategies to achieve endovascular false lumen occlusion are of increasing importance and novel techniques have been introduced to solve the problem of persisting false lumen flow. Thus, the evolution of a large variety of techniques to address the false lumen perfusion issue indicates that complicated chronic type B dissection involves a high diversity in clinical presentation and morphology. A large armamentarium of catheter skills as well as critical individualized treatment strategies are required to address the heterogenous morphological disease

  11. Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 MAP Kinase

    PubMed Central

    Wu, Jing; Thabet, Salim R.; Kirabo, Annet; Trott, Daniel W.; Saleh, Mohamed A.; Xiao, Liang; Madhur, Meena S.; Chen, Wei; Harrison, David G.

    2014-01-01

    Rationale Aortic stiffening commonly occurs in hypertension and further elevates systolic pressure. Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch and aortic stiffening in hypertension remains undefined. Objective To determine the role of inflammation and mechanical stretch in aortic stiffening. Methods and Results Chronic angiotensin II infusion caused marked aortic adventitial collagen deposition, as quantified by Masson’s Trichrome Blue staining and biochemically by hydroxyproline content, in wild-type (WT) but not in Recombination Activation Gene-1 deficient (RAG-1−/−) mice. Aortic compliance, defined by ex-vivo measurements of stress-strain curves, was reduced by chronic angiotensin II infusion in WT mice (p<0.01) but not in RAG-1−/− mice (p<0.05). Adoptive transfer of T cells to RAG-1−/− mice restored aortic collagen deposition and stiffness to values observed in WT mice. Mice lacking the T cell derived cytokine IL-17a were also protected against aortic stiffening. In additional studies, we found that blood pressure normalization by treatment with hydralazine and hydrochlorothiazide prevented angiotensin II-induced vascular T cell infiltration, aortic stiffening and collagen deposition. Finally, we found that mechanical stretch induces expression of collagen 1α1, 3α1 and 5a1 in cultured aortic fibroblasts in a p38 MAP kinase-dependent fashion, and that inhibition of p38 prevented angiotensin II-induced aortic stiffening in vivo. IL-17a also induced collagen 3a1 expression via activation of p38 MAP kinase. Conclusions Our data define a pathway in which inflammation and mechanical stretch lead to vascular inflammation that promotes collagen deposition. The resultant increase in aortic stiffness likely further worsens systolic hypertension and its attendant end-organ damage. PMID:24347665

  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. Tribbles 3: A potential player in diabetic aortic remodelling.

    PubMed

    Ti, Yun; Xie, Guo-lu; Wang, Zhi-hao; Ding, Wen-yuan; Zhang, Yun; Zhong, Ming; Zhang, Wei

    2016-01-01

    Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes. PMID:26410836

  14. Aortic Stenosis, a Left Ventricular Disease: Insights from Advanced Imaging.

    PubMed

    Badiani, Sveeta; van Zalen, Jet; Treibel, Thomas A; Bhattacharyya, Sanjeev; Moon, James C; Lloyd, Guy

    2016-08-01

    Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence. It is increasingly clear that it is also a disease of the left ventricle (LV) rather than purely the aortic valve. The transition from left ventricular hypertrophy to fibrosis results in the eventual adverse effects on systolic and diastolic function. Appropriate selection of patients for aortic valve intervention is crucial, and current guidelines recommend aortic valve replacement in severe AS with symptoms or in asymptomatic patients with left ventricular ejection fraction (LVEF) <50 %. LVEF is not a sensitive marker and there are other parameters used in multimodality imaging techniques, including longitudinal strain, exercise stress echo and cardiac MRI that may assist in detecting subclinical and subtle LV dysfunction. These findings offer potentially better ways to evaluate patients, time surgery, predict recovery and potentially offer targets for specific therapies. This article outlines the pathophysiology behind the LV response to aortic stenosis and the role of advanced multimodality imaging in describing it. PMID:27384950

  15. 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

  16. Contributing Mechanisms of Aortic Atheroma in Ischemic Cerebrovascular Disease.

    PubMed

    Kong, Qi; Ma, Xin

    2015-12-01

    In recent years, the correlation between aortic atheroma (AA) and the occurrence and recurrence of ischemic cerebrovascular disease (ICVD) has attracted much attention, but the contributory mechanisms remain controversial. This review analyzes related research on the roles of AA in ICVD, and demonstrates the correlation between the formation and development of AA and abnormal metabolism, inflammation, hemodynamic changes, and other contributory factors. The presence of complex aortic plaque (CAP) in the ascending aorta and aortic arch increases the risk of cerebral embolism and degree of injury, while the association between CAP in the descending aorta and cerebral embolism remains ambiguous. AA also functions as an indicator of atherosclerosis burden as well as hypercoagulability, which may further increase the risk of ICVD. Further study on the relationship of AA to ICVD will improve diagnosis and treatment in clinical practice. PMID:26522269

  17. [Aortic intramural hematoma. An atypical pattern equivalent to aortic dissection].

    PubMed

    López-Mínguez, J R; Merchán, A; Arrobas, J; Fernández, G; González-Egüaras, M; García-Andoaín, J M; Alonso, M; Gamero, C; Poblador, M A; Alonso, F

    1995-09-01

    A case is presented of a hypertensive woman who had suffered a stabbing back pain for some three hours, with mild irradiation to precordium and accompanied by vegetative signs. A sinusal rhythm and negative T waves of little depth were seen on the ECG. A transthoracic bidimensional echocardiogram (TTE) showed a normal left ventricle with a somewhat dilated aortic root and the existence of a double echo running parallel to the anterior wall of the aorta but non-ondulating and without a visible intimal flap. Because of suspected aortic dissection an urgent contrasted CAT and a transesophageal echocardiogram were performed. These were informed as an aneurysm of the aortic root with mural thrombus from the ascending to descending aorta, but with no existing intimal flap suggesting dissection. A cardiac catheterization showed a mildly some dilated aortic root without dissection signs and normal left ventricle and coronary arteries. The patient was presented for surgical evaluation but, since no dissection was present, was not considered urgent surgery; she was admitted to the coronary unit and died 48 hours later in a situation of acute pericardial tamponade, documented by TTE, surely due to rupture of the aortic root to pericardial sack. This way of presenting threatened aorta rupture that has been only recently recognized is discussed, as well as some misconceptions which must be avoided. PMID:7569267

  18. 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.

  19. 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

  20. Abdominal aortic aneurysm repair - open - discharge

    MedlinePlus

    AAA - open - discharge; Repair - aortic aneurysm - open - discharge ... You had open aortic aneurysm surgery to repair an aneurysm (a widened part) in your aorta, the large artery that carries blood to your ...

  1. Imaging of abdominal aortic aneurysms.

    PubMed

    Sparks, Amy R; Johnson, Philip L; Meyer, Mark C

    2002-04-15

    Given the high rate of morbidity and mortality associated with abdominal aortic aneurysms (AAAs), accurate diagnosis and preoperative evaluation are essential for improved patient outcomes. Ultrasonography is the standard method of screening and monitoring AAAs that have not ruptured. In the past, aortography was commonly used for preoperative planning in the repair of AAAs. More recently, computed tomography (CT) has largely replaced older, more invasive methods. Recent advances in CT imaging technology, such as helical CT and CT angiography, offer significant advantages over traditional CT. These methods allow for more rapid scans and can produce three-dimensional images of the AAA and important adjacent vascular structures. Use of endovascular stent grafts has increased recently and is less invasive for the repair of AAAs in selected cases. Aortography and CT angiography can precisely determine the size and surrounding anatomy of the AAA to identify appropriate candidates for the use of endovascular stent grafts. Helical CT and CT angiography represent an exciting future in the preoperative evaluation of AAAs. However, this technology is not the standard of care because of the lack of widespread availability, the cost associated with obtaining new equipment, and the lack of universal protocols necessary for acquisition and reconstruction of these images. PMID:11989632

  2. Relation of Aortic Valve Morphologic Characteristics to Aortic Valve Insufficiency and Residual Stenosis in Children With Congenital Aortic Stenosis Undergoing Balloon Valvuloplasty.

    PubMed

    Petit, Christopher J; Gao, Kevin; Goldstein, Bryan H; Lang, Sean M; Gillespie, Scott E; Kim, Sung-In H; Sachdeva, Ritu

    2016-03-15

    Aortic valve morphology has been invoked as intrinsic to outcomes of balloon aortic valvuloplasty (BAV) for congenital aortic valve stenosis. We sought to use aortic valve morphologic features to discriminate between valves that respond favorably or unfavorably to BAV, using aortic insufficiency (AI) as the primary outcome. All patients who underwent BAV at 2 large-volume pediatric centers from 2007 to 2014 were reviewed. Morphologic features assessed on pre-BAV echo included valve pattern (unicuspid, functional bicuspid, and true bicuspid), leaflet fusion length, leaflet excursion angle, and aortic valve opening area and on post-BAV echo included leaflet versus commissural tear. Primary end point was increase in AI (AI+) of ≥2°. Eighty-nine patients (median age 0.2 years) were included in the study (39 unicuspid, 41 functional bicuspid, and 9 true bicuspid valves). Unicuspid valves had a lower opening area (p <0.01) and greater fusion length (p = 0.01) compared with functional and true bicuspid valves. Valve gradient pre-BAV and post-BAV were not different among valve patterns. Of the 16 patients (18%) with AI+, 14 had leaflet tears (odds ratio 13.9, 3.8 to 50). True bicuspid valves had the highest rate (33%) of AI+. On multivariate analysis, leaflet tears were associated with AI+, with larger opening area pre-BAV and lower fusion length pre-BAV. AI+ was associated with larger pre-BAV opening area. Gradient relief was associated with reduced angle of excursion. Valve morphology influences outcomes after BAV. Valves with lesser fusion and larger valve openings have higher rates of leaflet tears which in turn are associated with AI. PMID:26805657

  3. Calcification of the aortic wall in hypercalcemic rabbits.

    PubMed

    Rokita, E; Cichocki, T; Divoux, S; Gonsior, B; Höfert, M; Jarczyk, L; Strzałkowski, A

    1992-10-01

    The mineralization process was investigated in the aortic wall of hypercalcemic rabbits. The elevated calcium level in serum was induced by intramuscular injection of vitamin D3. The animals were killed at different times of the experiment (max. 246 d). The freeze-dried tissue homogenates were used for elemental composition studies by means of proton induced X-ray emission (PIXE) and atomic absorption spectroscopy. The structural information was obtained from infrared (IR) and X-ray diffraction (XRD) spectra. Moreover, the ascending part of the aortic arch was separated and used for micro-PIXE (PIXE in combination with proton microprobe) and histochemical examinations. It was found that hypercalcemia (blood serum Ca content elevated by about 20%) induced calcification of the aortic wall. The mineral phase within the aortic wall consisted of Ca-P salts. The Ca/P ratio continuously increased during the experiment and approached 2 after 246 d of the vitamin D3 treatment. The IR and XRD studies made possible the identification of the complex phase composition of the samples. The hydroxyapatite crystals were detected after 196 days, however, in earlier phases of the experiment, amorphous calcium phosphate, dicalcium phosphate dihydrate and octacalcium phosphate were also observed. On the basis of the data obtained, the mechanism of the precipitation and growth of inorganic deposits in the tunica media of the aortic wall was discussed. PMID:1333314

  4. Which patients benefit from stentless aortic valve replacement?

    PubMed

    Gulbins, Helmut; Reichenspurner, Hermann

    2009-12-01

    This review article analyzes the literature to answer the question of whether stentless aortic bioprostheses possess proven advantages compared with stented bioprosthesis, and which patients might benefit from stentless valve implantation. For this purpose, the United States National Library of Medicine's PubMed and MEDLINE databases were searched for articles dealing with results of stentless aortic bioprostheses or studies comparing stented and stentless prostheses. Key word searches used were as follows: stentless aortic prostheses, stented aortic prosthesis, hemodynamic, hemodynamic performance, degeneration, durability, technique, and long-term follow-up. The analysis focused on stentless prostheses with a clinical experience for more than 5 years. Only a few randomized studies were found. Stentless prostheses were found to be advantageous in patients with severe impaired left ventricular function or a small aortic annulus (ie, evidence of grade II), but no specific advantages could be determined for the majority of patients. The durability results were mixed: the Toronto SPV (St. Jude Medical, Minneapolis, MN) showed an increase in degeneration after 10 years of follow-up, whereas the Freestyle porcine stentless prostheses (Medtronic, Minneapolis, MN) still showed excellent results after this period. PMID:19932303

  5. 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

  6. 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

  7. 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

  8. Abdominal aortic feminism.

    PubMed

    Mortimer, Alice Emily

    2014-01-01

    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. PMID:25398912

  9. 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

  10. 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. PMID:27314956

  11. 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

  12. Persistent Fifth Aortic Arch with Coarctation

    PubMed Central

    Kim, Sue Hyun; Choi, Eun-Suk; Cho, Sungkyu; Kim, Woong-Han

    2016-01-01

    Persistent fifth aortic arch (PFAA) is a rare congenital anomaly of the aortic arch frequently associated with other cardiovascular anomalies, such as tetralogy of Fallot and aortic arch coarctation or interruption. We report the case of a neonate with PFAA with coarctation who successfully underwent surgical repair. PMID:26889445

  13. 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

  14. 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

  15. Prognosis of supravalve aortic stenosis in 81 patients in Liverpool (1960-1993).

    PubMed Central

    Kitchiner, D.; Jackson, M.; Walsh, K.; Peart, I.; Arnold, R.

    1996-01-01

    OBJECTIVE: To determine the prognosis of supravalve aortic stenosis into early adult life and the factors affecting this prognosis. DESIGN: 81 patients with supravalve aortic stenosis were followed for a median duration of 8.3 (range 1 to 29) years. PATIENTS: 40 patients (49.4%) had Williams' syndrome, 18 (22.2%) familial supravalve aortic stenosis, 18 (22.2%) sporadic supravalve aortic stenosis, and five (6.2%) other syndromes. Nineteen patients had additional levels of left ventricular outflow tract obstruction. RESULTS: 47 patients (58%) underwent operation; 20% within a year of presentation. Multivariable analysis predicted that 88% of patients would undergo intervention within 30 years of follow up. The chance of intervention was increased by more severe aortic stenosis at presentation and the presence of multilevel obstruction in patients with sporadic supravalve aortic stenosis. Three deaths occurred before operation and 13 within a month of operation. Ten (62.5%) of the postoperative deaths were in patients with multilevel obstruction. Predicted survival 30 years after presentation was 66%. Risk factors for survival were age and severity of aortic stenosis at presentation. Multilevel obstruction did not emerge as a significant risk factor for death because of the high association with the severity of stenosis at presentation. 74% of survivors had mild or insignificant stenosis at follow up. CONCLUSIONS: Long-term survival is related to age and the severity of aortic stenosis at presentation. Most patients will require intervention, and most survivors will have mild stenosis. PMID:8705769

  16. 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.

  17. Aortitis causing rapid growth of a mycotic aortic aneurysm

    PubMed Central

    Williams, Zoheb Berry; Ryden, Lauren E.; Organ, Nicole M.

    2016-01-01

    Mycotic infrarenal aortic aneurysms are rare and often masquerade as other abdominal pathology. We present a case where serial imaging made the diagnosis and provided an insight into the pathophysiology of mycotic aneurysm. A 71-year-old man presents with abdominal pain, rigours and dysuria. Computed tomography reveals an irregular, thickened ectatic abdominal aorta, but cholescintigraphy suggests acalculous cholecystitis. Deterioration prompts repeat radiographical assessment, which demonstrates an increase in the size of the aorta over 10 days. The patient was treated emergently with an open aortic ligation, debridement and extra-anatomical bypass. Infections account for up to 2% of abdominal aortic aneurysms. The rate of growth of mycotic aneurysms is sparsely discussed in the literature and to our knowledge, there are no reports with serial single-modality imaging. The most significant finding was rapid expansion in aneurysm size. While mycotic aneurysm requires urgent treatment, diagnosis can be delayed and difficult. PMID:27009324

  18. Cystatin C deficiency in human atherosclerosis and aortic aneurysms

    PubMed Central

    Shi, Guo-Ping; Sukhova, Galina K.; Grubb, Anders; Ducharme, Anique; Rhode, Luis H.; Lee, Richard T.; Ridker, Paul M.; Libby, Peter; Chapman, Harold A.

    1999-01-01

    The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease. PMID:10545518

  19. Role of Echocardiography Before Transcatheter Aortic Valve Implantation (TAVI).

    PubMed

    Badiani, Sveeta; Bhattacharyya, Sanjeev; Lloyd, Guy

    2016-04-01

    Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence; transcatheter aortic valve implantation (TAVI) has become an accepted alternative to surgical aortic valve replacement (AVR) in the high risk or inoperable patient. Appropriate selection of patients for TAVI is crucial and requires a multidisciplinary approach including cardiothoracic surgeons, interventional cardiologists, anaesthetists, imaging experts and specialist nurses. Multimodality imaging including echocardiography, CT and MRI plays a pivotal role in the selection and planning process; however, echocardiography remains the primary imaging modality used for patient selection, intra-procedural guidance, post-procedural assessment and long-term follow-up. The contribution that contemporary transthoracic and transoesophageal echocardiography make to the selection and planning of TAVI is described in this article. PMID:26960423

  20. 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

  1. Transcatheter aortic valve implantation: from fantasy to reality

    PubMed Central

    2014-01-01

    Increased life expectancy has led to the presentation of more complicated patients in old age for the replacement of the aortic valve. The emergence of Transcatheter Aortic Valve Implantation (TAVI) was considered as a significant breakthrough in the management of symptomatic, moribund patients suffering from aortic valve stenosis who had been rejected for surgical intervention. A novel technology often has a long journey from the point at which it is created to its every-day-use. It is now obvious that TAVI practice in multiple institutes around the world has gone beyond the evidence. Serious concerns have been raised questioning the current TAVI practice. Analysis of future TAVI use may assist clinicians and healthcare managers to understand and deploy this technology in accordance with the evidence. PMID:24602509

  2. 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

  3. Imaging and minimally invasive aortic valve replacement

    PubMed Central

    Loor, Gabriel

    2015-01-01

    Cardiovascular imaging has been the most important tool allowing for innovation in cardiac surgery. There are now a variety of approaches available for treating aortic valve disease, including standard sternotomy, minimally invasive surgery, and percutaneous valve replacement. Minimally invasive cardiac surgery relies on maximizing exposure within a limited field of view. The complexity of this approach is increased as the relationship between the great vessels and the bony thorax varies between individuals. Ultimately, the success of minimally invasive surgery depends on appropriate choices regarding the type and location of the incision, cannulation approach, and cardioprotection strategy. These decisions are facilitated by preoperative imaging, which forms the focus of this review. PMID:25694979

  4. Aortic Root Calcification: A Possible Imaging Biomarker of Coronary Atherosclerosis.

    PubMed

    Nafakhi, Hussein; Al-Nafakh, Hasan A; Al-Mosawi, Abdulameer A

    2016-04-01

    It has been reported that coronary atherosclerosis risk assessment using coronary artery calcium and thoracic aorta calcium quantification may improve risk stratification as it can lead to the reclassification of persons at increased risk. The aortic root has been characterized by its close anatomical proximity to the ostial origins of the right and left coronary arteries, and it can be evaluated using multi-detector computed tomography without additional radiation exposure and the use of contrast. The correlations between aortic root calcification and coronary atherosclerotic markers as well as cardiac risk factors have been analyzed. PMID:27195236

  5. Aneurysm growth after late conversion of thoracic endovascular aortic repair

    PubMed Central

    Hayashi, Ichiro; Haijima, Norimasa

    2015-01-01

    A 69-year-old man underwent thoracic endovascular aortic repair of a descending aortic aneurysm. Three years later, he developed impending rupture due to aneurysmal expansion that included the proximal landing zone. Urgent open surgery was performed via lateral thoracotomy, and a Dacron graft was sewn to the previous stent graft distally with Teflon felt reinforcement. Postoperatively, four sequential computed tomography scans demonstrated that the aneurysm was additionally increasing in size probably due to continuous hematoma production, suggesting a possibility of endoleaks. This case demonstrates the importance of careful radiologic surveillance after endovascular repair, and also after partial open conversion. PMID:27489673

  6. Aortic Root Calcification: A Possible Imaging Biomarker of Coronary Atherosclerosis

    PubMed Central

    Nafakhi, Hussein; Al-Nafakh, Hasan A.; Al-Mosawi, Abdulameer A.

    2016-01-01

    It has been reported that coronary atherosclerosis risk assessment using coronary artery calcium and thoracic aorta calcium quantification may improve risk stratification as it can lead to the reclassification of persons at increased risk. The aortic root has been characterized by its close anatomical proximity to the ostial origins of the right and left coronary arteries, and it can be evaluated using multi-detector computed tomography without additional radiation exposure and the use of contrast. The correlations between aortic root calcification and coronary atherosclerotic markers as well as cardiac risk factors have been analyzed. PMID:27195236

  7. 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.

  8. [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. PMID:27295772

  9. 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

  10. 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

  11. 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

  12. BIOMECHANICS OF ABDOMINAL AORTIC ANEURYSM

    PubMed Central

    Vorp, David A.

    2009-01-01

    Abdominal aortic aneurysm (AAA) is a condition whereby the terminal aorta permanently dilates to dangerous proportions, risking rupture. The biomechanics of AAA has been studied with great interest since aneurysm rupture is a mechanical failure of the degenerated aortic wall and is a significant cause of death in developed countries. In this review article, the importance of considering the biomechanics of AAA is discussed, and then the history and the state-of-the-art of this field is reviewed - including investigations into the biomechanical behavior of AAA tissues, modeling AAA wall stress and factors which influence it, and the potential clinical utility of these estimates in predicting AAA rupture. PMID:17254589

  13. 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

  14. Online network of subspecialty aortic disease experts: Impact of "cloud" technology on management of acute aortic emergencies.

    PubMed

    Schoenhagen, Paul; Roselli, Eric E; Harris, C Martin; Eagleton, Matthew; Menon, Venu

    2016-07-01

    For the management of acute aortic syndromes, regional treatment networks have been established to coordinate diagnosis and treatment between local emergency rooms and central specialized centers. Triage of acute aortic syndromes requires definitive imaging, resulting in complex data files. Modern information technology network structures, specifically "cloud" technology, coupled with mobile communication, increasingly support sharing of these data in a network of experts using mobile, online access and communication. Although this network is technically complex, the potential benefit of online sharing of data files between professionals at multiple locations within a treatment network appear obvious; however, clinical experience is limited, and further evaluation is needed. PMID:27012454

  15. Association of G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco

    PubMed Central

    Hassani Idrissi, Hind; Hmimech, Wiam; Diakite, Brehima; Korchi, Farah; Baghdadi, Dalila; Habbal, Rachida; Nadifi, Sellama

    2016-01-01

    Background Myocardial infarction (MI) is a common multifactorial disease. Numerous studies have found that genetic plays an essential role in MI occurrence. The main objective of our case–control study is to explore the association of G894T eNOS (rs1799983), 4G/5G PAI (rs1799889) and T1131C APOA5 (rs662799) polymorphisms with MI susceptibility in the Moroccan population. Methods and results 118 MI patients were recruited vs 184 healthy controls. DNA samples were genotyped by PCR-RFLP method using MboI, BslI and MseI restriction enzymes respectively for the G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms. Our results show that the G894T eNOS was significantly associated with increased risk of MI under the three genetic transmission models (dominant: OR = 1.64, 95% CI = 1.05–2.58, P = 0.003; recessive: OR = 2.15, 95% CI = 0.74–6.16, P = 0.03; additive: OR = 1.54, 95% CI = 1.06–2.23, P = 0.001). The T1131C APOA5 polymorphism was associated to MI risk in recessive and additive models (OR = 1.53, 95% CI = 0.72–3.2, P = 0.04 and OR = 1.78, 95% CI = 1.26–2.51, P = 0.03 respectively). For the 4G/5G PAI variant, even the cases and controls groups were not in Hardy–Weinberg Equilibrium (HWE), the dominant and additive models show a statistically significant association with MI risk (OR = 7.96, 95%CI = 3.83–16.36, P = 0.01 and OR = 1.96, 95% CI = 1.4–2.72, P = 0.03 respectively). Conclusion Our results suggest that G894T eNOS and T1131C APOA5 polymorphisms may be considered as genetic markers of MI among the Moroccan population. Further studies including larger sample sizes and exploring more genetic associations are needed to confirm our results and to better understand the susceptibility to MI. PMID:27222817

  16. CT of nontraumatic thoracic aortic emergencies.

    PubMed

    Bhalla, Sanjeev; West, O Clark

    2005-10-01

    Computed tomography (CT), especially multidetector row CT (MDCT), is often the preferred imaging test used for evaluation of nontraumatic thoracic aortic abnormalities. Unenhanced images, usually followed by contrast-enhanced arterial imaging, allow for rapid detailed aortic assessment. Understanding the spectrum of acute thoracic aortic conditions which may present similarly (aortic dissection, aneurysm rupture, penetrating atherosclerotic ulcer, intramural hematoma) will ensure that patients are diagnosed and treated appropriately. Familiarity with imaging protocols and potential mimics will prevent confusion of normal anatomy and variants with aortic disease. PMID:16274000

  17. Hydatid cyst involving the aortic arch.

    PubMed

    Apaydin, Anil Z; Oguz, Emrah; Zoghi, Mehdi

    2007-03-01

    We report a very rare case of primary mediastinal hydatid cyst which invaded the ascending aorta and the aortic arch which initially presented as a cranial mass. Aortic wall is a very unusual site for the hydatid cysts. To the best of our knowledge, this is the first reported case of hydatid cyst located within the aortic arch lumen. Patient underwent ascending aortic and hemiarch replacement under hypothermic circulatory arrest and removal of the cyst. Patient had an uneventful recovery and has been on follow-up. Although the literature data are very limited, we believe that the aortic procedure of choice should be graft interpositon rather than patch repair. PMID:17215134

  18. 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

  19. 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

  20. eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus.

    PubMed

    Dincel, Gungor Cagdas; Kul, Oguz

    2015-10-01

    In this study, apoptotic and anti-apoptotic mechanisms and if present, which pathway to trigger the apoptosis in the brains of Border Disease Virus (BDV) infected lambs (n=10) and goat kids (n=5) were investigated. Briefly, apoptotic (caspase 3, caspase 9) and anti-apoptotic markers (Bcl-2), cytokine response (TNF-α, INF-γ), reactive gliosis and myelin loss were examined. eNOS, iNOS, caspase 9, caspase 3 and GFAP expressions were higher in BDV infected tissues compared to control animals (6 kids and 6 lambs) (p<0.05). Double immunoperoxidase test revealed that TUNEL positive apoptotic cells showed significant association with increased eNOS-iNOS and iNOS-BDV expressions. However, no significant differences were found for TNFR1, TNF-α and INF-γ expressions in BD (p>0.05). There was a positive correlation between the intensity of myelin loss, GFAP activity and severity of infection. Inconclusion, as a novel finding, it is established that eNOS and iNOS overexpressions are co-associated with apoptosis in BDV infected neurons and neuroglia. The results also strongly suggested that BDV infected apoptotic cells mainly prefer the intrinsic pathway that might be most likely related to increased nitric oxide levels. PMID:25882134

  1. [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

  2. Reliability of aortic aneurysm screening measurements

    PubMed Central

    Evans, Tony; Wolstenhulme, Stephen

    2013-01-01

    The aim of this feasibility study was to assess the impact that image processing of abdominal aortic ultrasound (US) images had on the intra-observer reliability of the diameter measurement. The study compared variability between inner-to-inner (ITI), outer-to-outer (OTO) and outer-to-inner (OTI) wall diameter measurements and their resilience to image processing. Three US images of transverse abdominal aortas were manipulated in 13 different ways using functions from Image J software (National Institutes of Health, Bethesda, MD, USA). Blinded measurements were performed of the aortic diameters from each image; this was repeated for ITI, OTO and OTI. Profiles of each image were produced and sets of rules developed to provide detailed instructions as to where, on the profile, the callipers should be placed to correspond with the actual image. The reliability of the diameter measurements compared to the original diameter measurement was least affected by adjusting the brightness and contrast of the US images (better than ± 1.5 mm). Using the functions ‘Sharpen’ and ‘Find Edges’ created the largest difference (up to −5 mm). The ITI measurements had the widest spread of variability, whereas the OTI measurements proved to be the most repeatable and resilient to image processing. This study suggests the precision of the measurements can be kept within satisfactory levels even after image manipulation. It also showed the most reliable measuring guideline was OTI, in contrast to the guideline currently used by the NHS Abdominal Aortic Aneurysm Screening Programme. Further research is needed to transfer the findings into the clinical setting of the National Screening Programme to increase its reliability.

  3. 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

  4. Visceral Infarction Following Aortic Surgery

    PubMed Central

    Johnson, Willard C.; Nabseth, Donald C.

    1974-01-01

    An experience with aortic surgery is reported which reveals that visceral ischemia is more frequent than expected and significantly contributes to operative mortality. Two of five deaths among 84 patients who had aorto-iliac occlusive disease and four of 40 deaths among 103 aneurysmectomies (both ruptured and elective) were related to visceral ischemia. A review of the literature reveals 99 cases of colonic ischemia in more than 6,100 cases of aortic surgery, an incidence of 1.5%. Only 10 cases of small bowel ischemia were recorded. The present experience with 9 cases of colon ischemia and one of small bowel ischemia is presented particularly with reference to pathophysiology and prevention. It is concluded that patients should be identified by appropriate angiography if considered a risk for visceral infarction, and, if present, visceral arterial reconstruction should be performed in addition to aortic reconstructive surgery. Colon infarction following aortic aneurysmal surgery is directly related to ligation of a patent IMA. Thus re-implantation of the patent IMA should be considered. ImagesFig. 1a. PMID:4277757

  5. 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

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

    PubMed

    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

  7. Aortic Root Enlargement with Ascending-to-Descending Aortic Bypass in Repair of Coarctation.

    PubMed

    Perry, Paul A; Young, Nilas

    2015-07-01

    Ascending-to-descending aortic bypass is a valuable technique for addressing coarctation of the aorta when additional cardiac procedures are indicated in adults. Among these, aortic valve replacement is one of the most commonly performed concomitant procedures, and there are instances in which aortic root enlargement is required. Herein, a novel technique is described for performing simultaneous ascending-to-descending aortic bypass in conjunction with aortic root enlargement which incorporates the bypass graft as part of the aortic root enlargement. PMID:26897826

  8. Safety of elective management of synchronous aortic disease with simultaneous thoracic and aortic stent graft placement

    PubMed Central

    Scali, Salvatore T.; Feezor, Robert J.; Chang, Catherine K.; Stone, David H.; Goodney, Philip P.; Nelson, Peter R.; Huber, Thomas S.; Beck, Adam W.

    2013-01-01

    Background Simultaneous treatment of multilevel aortic disease is controversial due to the theoretic increase in morbidity. This study was conducted to define the outcomes in patients treated electively with simultaneous thoracic endovascular aortic aneurysm repair (TEVAR) and abdominal aortic endovascular endografting for synchronous aortic pathology. Methods Patients treated with simultaneous TEVAR and endovascular aneurysm repair (T&E) at the University of Florida were identified from a prospectively maintained endovascular aortic registry and compared with those treated with TEVAR alone (TA). The study excluded patients with urgent or emergency indications, thoracoabdominal or mycotic aneurysm, and those requiring chimney stents, fenestrations, or visceral debranching procedures. Demographics, anatomic characteristics, operative details, and periprocedural morbidity were recorded. Mortality and reintervention were estimated using life-table analysis. Results From 2001 to 2011, 595 patients underwent TEVAR, of whom 457 had elective repair. Twenty-two (18 men, 82%) were identified who were treated electively with simultaneous T&E. Mean ± standard deviation age was 66 ± 9 years, and median follow-up was 8.8 months (range, 1–34 months). Operative indications for the procedure included dissection-related pathology in 10 (45%) and various combinations of degenerative etiologies in 12 (55%). Compared with TA, T&E patients had significantly higher blood loss (P < .0001), contrast exposure (P < .0001), fluoroscopy time (P < .0001), and operative time (P < .0001). The temporary spinal cord ischemia rate was 13.6% (n = 3) for the T&E group and 6.0% for TA (P = .15); however, the permanent spinal cord ischemia rate was 4% for both groups (P = .96). The 30-day mortality for T&E was 4.5% (n = 1) compared with 2.1% (n = 10) for TA. Temporary renal injury (defined by a 25% increase over baseline creatinine) occurred in two T&E patients (9.1%), with none requiring permanent

  9. Hemoglobin α / eNOS Coupling at Myoendothelial Junctions is Required for Nitric Oxide Scavenging During Vasoconstriction

    PubMed Central

    Straub, Adam C.; Butcher, Joshua T.; Billaud, Marie; Mutchler, Stephanie M.; Artamonov, Mykhaylo V.; Nguyen, Anh T.; Johnson, Tyler; Best, Angela K.; Miller, Megan P.; Palmer, Lisa A.; Columbus, Linda; Somlyo, Avril V.; Le, Thu H.; Isakson, Brant E.

    2014-01-01

    Objective Hb α and eNOS form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates NO signaling, vascular reactivity and blood pressure using a mimetic peptide of Hb α to disrupt this interaction. Approach and Results In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Utilizing in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. FITC-labeling of Hb α X revealed localization to holes in the internal elastic lamina (i.e., myoendothelial junctions). To test the functional effects of Hb α X, we measured cGMP and vascular reactivity. Our results reveal augmented cGMP production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X which caused a significant decrease in blood pressure; injection of Hb α X into eNOS−/− mice had no effect. Conclusion These results identify a novel sequence on Hb α that is important for Hb α / eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions. PMID:25278292

  10. 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

  11. 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

  12. Transcatheter, valve-in-valve transapical aortic and mitral valve implantation, in a high risk patient with aortic and mitral prosthetic valve stenoses

    PubMed Central

    Ramakrishna, Harish; DeValeria, Patrick A.; Sweeney, John P.; Mookaram, Farouk

    2015-01-01

    Transcatheter valve implantation continues to grow worldwide and has been used principally for the nonsurgical management of native aortic valvular disease-as a potentially less invasive method of valve replacement in high-risk and inoperable patients with severe aortic valve stenosis. Given the burden of valvular heart disease in the general population and the increasing numbers of patients who have had previous valve operations, we are now seeing a growing number of high-risk patients presenting with prosthetic valve stenosis, who are not potential surgical candidates. For this high-risk subset transcatheter valve delivery may be the only option. Here, we present an inoperable patient with severe, prosthetic valve aortic and mitral stenosis who was successfully treated with a trans catheter based approach, with a valve-in-valve implantation procedure of both aortic and mitral valves. PMID:25849702

  13. 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.

  14. Turbulence downstream of subcoronary stentless and stented aortic valves.

    PubMed

    Funder, Jonas Amstrup; Frost, Markus Winther; Wierup, Per; Klaaborg, Kaj-Erik; Hjortdal, Vibeke; Nygaard, Hans; Hasenkam, J Michael

    2011-08-11

    Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel wall as well as to aortic valve leaflets. Stentless aortic heart valves are known to posses several hemodynamic benefits such as larger effective orifice areas, lower aortic transvalvular pressure difference and faster left ventricular mass regression compared with their stented counterpart. Whether this is reflected by diminished turbulence formation, remains to be shown. We implanted either stented pericardial valve prostheses (Mitroflow), stentless valve prostheses (Solo or Toronto SPV) in pigs or they preserved their native valves. Following surgery, blood velocity was measured in the cross sectional area downstream of the valves using 10MHz ultrasonic probes connected to a dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at two different blood pressures (baseline and 50% increase). We found no difference in maximum RNS measurements between any of the investigated valve groups. The native valve had significantly lower mean RNS values than the Mitroflow (p=0.004), Toronto SPV (p=0.008) and Solo valve (p=0.02). There were no statistically significant differences between the artificial valve groups (p=0.3). The mean RNS was significantly larger when increasing blood pressure (p=0.0006). We, thus, found no advantages for the stentless aortic valves compared with stented prosthesis in terms of lower maximum or mean RNS values. Native valves have a significantly lower mean RNS value than all investigated bioprostheses. PMID:21696741

  15. Dynamic LVOT Obstruction and Aortic Stenosis in the Same Patient: A Case of Challenging Doppler Hemodynamics.

    PubMed

    Parker, Matthew W; Kiernan, Francis J

    2015-06-01

    We present a patient with both dynamic left ventricular outflow tract obstruction and valvular aortic stenosis. The aortic valve was calcified, and velocities and gradients measured by continuous-wave Doppler met standard criteria for severe aortic stenosis. The increased subvalvular velocities invalidated assumptions of the simplified Bernoulli equation; correction using the longer form of the Bernoulli equation suggested a lower but still significant gradient. The complex shape of the subvalvular spectral Doppler envelope indicated supranormal systolic function and dynamic left ventricular outflow obstruction. Left heart catheterization with an end-hole catheter was required to determine the subvalvular and valvular components of the obstruction. PMID:25809389

  16. A Simple Device for Morphofunctional Evaluation During Aortic Valve-Sparing Surgery.

    PubMed

    Leone, Alessandro; Bruno, Piergiorgio; Cammertoni, Federico; Massetti, Massimo

    2015-07-01

    Valve-sparing operations for the treatment of aortic root disease with a structurally normal aortic valve are increasingly performed as they avoid prosthesis-related complications. Short- and long-term results are critically dependent on perfect intraoperative restoration of valve anatomy and function. Residual aortic regurgitation is the main cause of early failure, and it is the most common motive for reoperation. However, intraoperative morphofunctional valve assessment requires expertise, and only transesophageal echocardiography can provide reliable information. We describe a simple, economic, reproducible hydrostatic test to intraoperatively evaluate valve competency under direct visualization. PMID:26140788

  17. Natural history of thoracic aortic aneurysms: size matters, plus moving beyond size.

    PubMed

    Chau, Katherine H; Elefteriades, John A

    2013-01-01

    Thoracic aortic aneurysms (TAAs) are a prevalent and deadly disease that, without diagnosis and treatment, eventuates in life-threatening aortic dissection or rupture. While TAAs normally grow in an indolent manner, once a certain size (a "hinge point") is reached, the risk of dissection, rupture, and death increases dramatically. By virtue of their common clinical "silence," many TAAs are not diagnosed until such complications occur. While size is a helpful criterion for intervention, there is a need for parameters and markers besides aortic aneurysm size for use in diagnosing and monitoring TAAs so as to prevent natural complications of this disease. PMID:23993240

  18. 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

  19. 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

  20. Transcatheter aortic valve implantation for failing surgical aortic bioprosthetic valve: from concept to clinical application and evaluation (part 1).

    PubMed

    Piazza, Nicolo; Bleiziffer, Sabine; Brockmann, Gernot; Hendrick, Ruge; Deutsch, Marcus-André; Opitz, Anke; Mazzitelli, Domenico; Tassani-Prell, Peter; Schreiber, Christian; Lange, Rüdiger

    2011-07-01

    With an aging population, improvement in life expectancy, and significant increase in the use of bioprosthetic valves, structural valve deterioration will become more and more prevalent. The operative mortality for an elective redo aortic valve surgery is reported to range from 2% to 7%, but this percentage can increase to more than 30% in high-risk and nonelective patients. Because transcatheter aortic valve (TAV)-in-surgical aortic valve (SAV) implantation represents a minimally invasive alternative to conventional redo surgery, it may prove to be safer and just as effective as redo surgery. Of course, prospective comparisons with a large number of patients and long-term follow-up are required to confirm these potential advantages. It is axiomatic that knowledge of the basic construction and dimensions, radiographic identification, and potential failure modes of SAV bioprostheses is fundamental in understanding key principles involved in TAV-in-SAV implantation. The goals of this paper are: 1) to review the classification, physical characteristics, and potential failure modes of surgical bioprosthetic aortic valves; and 2) to discuss patient selection and procedural techniques relevant to TAV-in-SAV implantation. PMID:21777879

  1. 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.

  2. 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

  3. Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS.

    PubMed

    Yuan, Qi; Yang, Jingyi; Santulli, Gaetano; Reiken, Steven R; Wronska, Anetta; Kim, Mindy M; Osborne, Brent W; Lacampagne, Alain; Yin, Yuxin; Marks, Andrew R

    2016-07-26

    Endothelial cells (ECs) are critical mediators of blood pressure (BP) regulation, primarily via the generation and release of vasorelaxants, including nitric oxide (NO). NO is produced in ECs by endothelial NO synthase (eNOS), which is activated by both calcium (Ca(2+))-dependent and independent pathways. Here, we report that intracellular Ca(2+) release from the endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptor (IP3R) is required for Ca(2+)-dependent eNOS activation. EC-specific type 1 1,4,5-trisphosphate receptor knockout (IP3R1(-/-)) mice are hypertensive and display blunted vasodilation in response to acetylcholine (ACh). Moreover, eNOS activity is reduced in both isolated IP3R1-deficient murine ECs and human ECs following IP3R1 knockdown. IP3R1 is upstream of calcineurin, a Ca(2+)/calmodulin-activated serine/threonine protein phosphatase. We show here that the calcineurin/nuclear factor of activated T cells (NFAT) pathway is less active and eNOS levels are decreased in IP3R1-deficient ECs. Furthermore, the calcineurin inhibitor cyclosporin A, whose use has been associated with the development of hypertension, reduces eNOS activity and vasodilation following ACh stimulation. Our results demonstrate that IP3R1 plays a crucial role in the EC-mediated vasorelaxation and the maintenance of normal BP. PMID:27402766

  4. 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

  5. Type B Aortic Dissection with Abdominal Aortic Aneurysm Rupture 1 Year after Endovascular Repair of Abdominal Aortic Aneurysm.

    PubMed

    Daniel, Guillaume; Ben Ahmed, Sabrina; Warein, Edouard; Gallon, Arnaud; Rosset, Eugenio

    2016-05-01

    We report a patient who developed a type B aortic dissection and ruptured his aneurysmal sac 1 year after endovascular abdominal aortic aneurysm repair (EVAR), despite standard follow-up. This 79-year-old man was presented to emergency room with acute abdominal pain and an acute lower limb ischemia. Computed tomography scan showed an acute type B aortic dissection feeding the aneurysmal sac of the EVAR. The aneurysm rupture occurred during imaging. Type B aortic dissection is a rare cause of aneurysmal rupture after EVAR. The first postoperative computed tomography scan should maybe include the arch and the descending thoracic aorta to rule out an iatrogenic dissection after EVAR. PMID:26902937

  6. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS

    PubMed Central

    Crabtree, Mark J.; Smith, Caroline L.; Lam, George; Goligorsky, Michael S.; Gross, Steven S.

    2009-01-01

    5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs). Oxidation of BH4, in the setting of diabetes and other chronic vasoinflammatory conditions, can cause cofactor insufficiency and uncoupling of endothelial NOS (eNOS), manifest by a switch from nitric oxide (NO) to superoxide production. Here we tested the hypothesis that eNOS uncoupling is not simply a consequence of BH4 insufficiency, but rather results from a diminished ratio of BH4 vs. its catalytically incompetent oxidation product, 7,8-dihydrobiopterin (BH2). In support of this hypothesis, [3H]BH4 binding studies revealed that BH4 and BH2 bind eNOS with equal affinity (Kd ≈ 80 nM) and BH2 can rapidly and efficiently replace BH4 in preformed eNOS-BH4 complexes. Whereas the total biopterin pool of murine endothelial cells (ECs) was unaffected by 48-h exposure to diabetic glucose levels (30 mM), BH2 levels increased from undetectable to 40% of total biopterin. This BH2 accumulation was associated with diminished calcium ionophore-evoked NO activity and accelerated superoxide production. Since superoxide production was suppressed by NOS inhibitor treatment, eNOS was implicated as a principal superoxide source. Importantly, BH4 supplementation of ECs (in low and high glucose-containing media) revealed that calcium ionophore-evoked NO bioactivity correlates with intracellular BH4: BH2 and not absolute intracellular levels of BH4. Reciprocally, superoxide production was found to negatively correlate with intracellular BH4:BH2. Hyperglycemia-associated BH4 oxidation and NO insufficiency was recapitulated in vivo, in the Zucker diabetic fatty rat model of type 2 diabetes. Together, these findings implicate diminished intracellular BH4:BH2, rather than BH4 depletion per se, as the molecular trigger for NO insufficiency in diabetes. PMID:18192221

  7. 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

  8. 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. PMID:25564325

  9. 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.

  10. 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

  11. Functional aortic stiffness: role of CD4+ T lymphocytes

    PubMed Central

    Majeed, Beenish A.; Eberson, Lance S.; Tawinwung, Supannikar; Larmonier, Nicolas; Secomb, Timothy W.; Larson, Douglas F.

    2015-01-01

    The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1−/− mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young's modulus in C57BL/6J mice by three-fold but caused no change in the RAG 1−/− mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1−/− mice. In order to account for the hydraulic vs. material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity (PWV) decreased from three- to two-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling. PMID:26379554

  12. In vitro study of the aortic interleaflet triangle reshaping.

    PubMed

    Vismara, R; Leopaldi, A M; Mangini, A; Romagnoni, C; Contino, M; Antona, C; Fiore, G B

    2014-01-22

    Aortic interleaflet triangle reshaping (AITR) is a surgical approach to aortic valve incontinence that involves placing three stitches at half of the interleaflet triangles height. In this work, the relationship between the actual stitch height and valve functioning, and the safety margin that the surgeon can rely on in applying the stitches were systematically investigated in vitro. AITR surgery was applied to six swine aortic roots placing the stitches empirically at 50%, 60% and 75% of the triangle heights. Then the actual stitch heights were measured and the hydrodynamic performances were evaluated with a pulsatile hydrodynamic mock loop. Actual stitch heights were 45±2%, 61±4% and 79±6%. As compared to untreated conditions, the 50% configuration induced a significant variation in the effective orifice area. With stitches placed at 60%, the mean systolic pressure drop increased significantly with respect to the untreated case, but no significant changes were recorded with respect to the 50% configuration. At 75%, all the hydrodynamic parameters of systolic valve functioning worsened significantly. Summarizing, the AITR technique, when performed in a conservative manner did not induce significant alterations in the hydrodynamics of the aortic root in vitro, while more aggressive configurations did. The absence of a statistically significant difference between the 50% and 60% configurations suggests that there is a reasonably limited risk of inducing valve stenosis in the post-op scenario due to stitch misplacement. PMID:24360769

  13. 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

  14. 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

  15. Treatment options for postdissection aortic aneurysms.

    PubMed

    Sobocinski, Jonathan; Patterson, Benjamin O; Clough, Rachel E; Spear, Rafaelle; Martin-Gonzalez, Teresa; Azzaoui, Richard; Hertault, Adrien; Haulon, Stéphan

    2016-04-01

    Aortic dissection is one of the most devastating catastrophes that can affect the aorta. Surgical treatment is proposed only when complications such as rupture or malperfusion occur. No clear consensus has been reached regarding the best therapy to prevent aortic rupture after the acute phase. We have performed a thorough review of the most recent literature on the strategies to treat patients in the chronic phase of aortic dissection. PMID:26771869

  16. Recurrent tamponade and aortic dissection in syphilis.

    PubMed

    Stansal, Audrey; Mirault, Tristan; Rossi, Aude; Dupin, Nicolas; Bruneval, Patrick; Bel, Alain; Azarine, Arshid; Minozzi, Catherine; Deman, Anne Laure; Messas, Emmanuel

    2013-11-01

    Syphilitic cardiovascular disease has been described since the 19th century, mainly on autopsy series. Major clinical manifestations are aortic aneurysm, aortic insufficiency, and coronary ostial stenosis. The diagnosis of syphilitic cardiovascular disease is based mainly on positive serologic tests and overt clinical manifestations. We present here a rare and unusual clinical presentation of a tertiary syphilis with recurrent tamponade and type B aortic dissection, whose positive diagnosis was made by polymerase chain reaction on pericardial fluid analysis. PMID:24182507

  17. 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. PMID:23161165

  18. Decreased platelet function in aortic valve stenosis: high shear platelet activation then inactivation.

    PubMed Central

    O'Brien, J. R.; Etherington, M. D.; Brant, J.; Watkins, J.

    1995-01-01

    OBJECTIVE--To elucidate the mechanism of the bleeding tendency observed in patients with aortic valve stenosis. DESIGN--A prospective study of high and low shear platelet function tests in vitro in normal controls compared with that in patients with severe aortic valve stenosis with a mean (SD) systolic gradient by Doppler of 75 (18) mm Hg before and at least 4 months after aortic valve replacement. SETTING--District general hospital. RESULTS--The patients showed reduced retention in the high shear platelet function tests. (a) Platelet retention in the filter test was 53.6 (12.6)% in patients with aortic valve stenosis and 84.8 (9.6)% in the controls (P < 0.001). (b) Retention in the glass bead column test was 49.8 (19.2) in the patients and 87.4 (8.7) in the controls (P < 0.001). (c) The standard bleeding time was longer in the patients (P < 0.06). Results of the high shear tests (a, b, and c) after aortic valve replacement were within the normal range. The platelet count was low but within the normal range before surgery and increased postoperatively (P < 0.01). There were no differences in the results of standard clotting tests, plasma and intraplatelet von Willebrand's factor, or in 15 platelet aggregation tests using five agonists between patients with aortic valve stenosis and controls. CONCLUSIONS--The high shear haemodynamics of aortic valve stenosis modify platelet function in vivo predisposing to a bleeding tendency. This abnormality of platelet function is detectable only in vitro using high shear tests. The abnormal function is reversed by aortic valve replacement. High shear forces in vitro activate and then inactivate platelets. By the same mechanisms aortic valve stenosis seems to lead to high shear damage in vivo, resulting in a clinically important bleeding tendency in some patients. PMID:8541170

  19. 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

  20. 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

  1. Aortic Aneurysm: Etiopathogenesis and Clinicopathologic Correlations

    PubMed Central

    2016-01-01

    Aortic aneurysm (AA) is one of the life-threatening aortic diseases, leading to aortic rupture of any cause including atherosclerotic and non-atherosclerotic diseases. AA is diagnosed in a variable proportion of patients with dilated aorta by imaging modality. The etiopathogenesis of AA remains unclear in many aortic diseases. Furthermore, although it may be difficult to explain all phenotypes of patients even if genetic mutation could be identified in some proteins such as smooth muscle cell α-actin (ACTA2), myosin heavy chain 11 (MYH11) or SMAD3, individualized consideration of these factors in each patient is essential on the basis of clinicopathological characteristics. PMID:27375798

  2. Practical genetics of thoracic aortic aneurysm.

    PubMed

    Elefteriades, John A; Pomianowski, Pawel

    2013-01-01

    This chapter will provide a practical look at the rapidly evolving field regarding the genetics of thoracic aortic aneurysm. It will start with a look at the history of the genetics of thoracic aortic aneurysm and will then move on to elucidating the discovery of familial patterns of thoracic aortic aneurysm. We will next review the Mendelian genetics of transmission of thoracic aortic aneurysm. We will move on to the molecular genetics at the DNA level and finish with a discussion of the molecular genetics at the RNA level, including a promising investigational "RNA Signature" test that we have been developing at Yale. PMID:23993238

  3. Brucellosis complicated by aortic valve endocarditis.

    PubMed

    Skillington, P D; McGiffin, D C; Kemp, R; Bett, J H; Holt, G; Forgan-Smith, R

    1988-12-01

    A 30 year old veterinary surgeon developed a febrile illness with serological evidence of Brucellosis. He was known to have aortic valve disease and during the course of the illness, the clinical features of endocarditis became evident, with a vegetation visible echocardiographically on the aortic valve. Because of persisting fever despite appropriate antibiotic therapy, aortic valve replacement with a viable cryopreserved allograft aortic valve was undertaken. Organisms consistent with Brucella species were demonstrated in the excised vegetation. The patient received a six week course of antibiotics and his post-operative course was uneventful. PMID:3250411

  4. 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.

  5. 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

  6. 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

  7. Emergency aortic valve replacement and Caesarian section in a primigravida with severe aortic stenosis: a case report

    PubMed Central

    Kochhar, Puneet K; Zutshi, V; Shamsunder, S; Batra, S; Ghosh, P

    2011-01-01

    Introduction Congenital bicuspid aortic valve with severe aortic stenosis (AS) is a rare condition (3–6% of patients with congenital heart disease). Pregnancy in these patients carries a high risk of maternal and fetal mortality. With advancing gestational age, these women may develop cardiac failure due to increased cardiorespiratory requirements. When medical therapy proves insufficient, cardiac surgery becomes mandatory to save the patient's life. Balloon valvuloplasty is only palliative treatment, the duration of benefit being only 6 months. Valve replacement is thus recommended. Cardiopulmonary bypass (CPB) surgery with valve replacement has been reported to carry a lower risk of maternal mortality (1.5–13%) but a very high fetal risk (16–40%). This paper reports the case of a 30-year-old primigravida with severe AS with bicuspid aortic valve and pulmonary congestion clinically uncontrolled, in whom CPB surgery and aortic valve replacement was performed as an emergency procedure, along with a lower segment Caesarian section. Conclusion The outcome of unrelieved severe symptomatic AS in pregnancy is poor. Multidisciplinary management is important to avoid deterioration in cardiac performance in parturients with severe AS. CPB during pregnancy carries a high risk to the fetus. Therefore, open heart surgery during pregnancy should be advised only in extreme emergencies (ie, heart failure refractory to conventional therapy).

  8. 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.

  9. 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

  10. High-order ENO schemes for unstructured meshes based on least-squares reconstruction

    SciTech Connect

    Ollivier-Gooch, C.F.

    1997-03-01

    High-order accurate schemes for conservation laws for unstructured meshes are not nearly so well advanced as such schemes for structured meshes. Consequently, little or nothing is known about the possible practical advantages of high-order discretization on unstructured meshes. This article is part of an ongoing effort to develop high-order schemes for unstructured meshes to the point where meaningful information can be obtained about the trade-offs involved in using spatial discretizations of higher than second-order accuracy on unstructured meshes. This article describes a high-order accurate ENO reconstruction scheme, called DD-L{sub 2}-ENO, for use with vertex-centered upwind flow solution algorithms on unstructured meshes. The solution of conservation equations in this context can be broken naturally into three phases: (1) solution reconstruction, in which a polynomial approximation of the solution is obtained in each control volume. (2) Flux integration around each control volume, using an appropriate flux function and a quadrature rule with accuracy commensurate with that of the reconstruction. (3) Time evolution, which may be implicit, explicit, multigrid, or some hybrid.

  11. Premature Bioprosthetic Aortic Valve Degeneration Associated with Allergy to Galactose-Alpha-1,3-Galactose.

    PubMed

    Hawkins, Robert B; Frischtak, Helena L; Kron, Irving L; Ghanta, Ravi K

    2016-07-01

    We present the cases of two patients with bioprosthetic aortic valves who developed an allergy to alpha-gal. Each had premature degeneration of their bioprosthesis and demonstrated rapidly increasing transvalvular gradients after development of their allergy. Each underwent successful replacement with a mechanical aortic valve within 1-2 years of symptom onset. doi: 10.1111/jocs.12764 (J Card Surg 2016;31:446-448). PMID:27238083

  12. 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

  13. Wave intensity analysis of para-aortic counterpulsation.

    PubMed

    Lu, Pong-Jeu; Yang, Chi-Fu Jeffrey; Wu, Meng-Yu; Hung, Chun-Hao; Chan, Ming-Yao; Hsu, Tzu-Cheng

    2012-04-01

    Wave intensity analysis (WIA) was used to delineate and maximize the efficacy of a newly developed para-aortic blood pump (PABP). The intra-aortic balloon pump (IABP) was employed as the comparison benchmark. Acute porcine experiments using eight pigs, randomly divided into IABP (n = 4) and PABP (n = 4) groups, were conducted to compare the characteristics of intra- and para-aortic counterpulsation. We measured pressure and velocity with probes installed in the left anterior descending coronary artery and aorta, during and without PABP assistance. Wave intensity for aortic and left coronary waves were derived from pressure and flow measurements with synchronization correction applied. To achieve maximized support efficacy, deflation timings ranging from 25 ms ahead of to 35 ms after the R-wave were tested. Similar to those associated with IABP counterpulsation, the PABP-generated backward-traveling waves predominantly drove aortic and coronary blood flows. However, in contrast with IABP counterpulsation, the nonocclusive nature of the PABP allowed systolic unloading to be delayed into early systole, which resulted in near elimination of coronary blood steal without diminution of systolic left ventricular ejection wave intensities. WIA can elucidate subtleties among different counterpulsatile support means with high sensitivity. Total accelerating wave intensity (TAWI), which was defined as the sum of the time integration of accelerated parts of the positive and negative wave intensities, was used to quantify counterpulsation efficacy. In general, the larger the TAWI gain, the better the counter-pulsatile support efficacy. However, when PABP deflation timings were delayed to after the R-wave, the TAWI was found to be inversely correlated with coronary perfusion. In this delayed deflation timing setting, greater wave cancellation occurred, which led to decreased TAWI but increased coronary perfusion attributed to blood regurgitation reduction. PMID:22227124

  14. 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. PMID:26487562

  15. 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

  16. 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

  17. [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) PMID:1483624

  18. 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. PMID:27383857

  19. Elevated Aortic Augmentation Index in Children Following Fontan Palliation: Evidence of Stiffer Arteries?

    PubMed

    Bhat, Deepti P; Gupta, Pooja; Aggarwal, Sanjeev

    2015-08-01

    Children born with a functional single ventricle who undergo Fontan palliation are prone to early pump failure. Whether they develop early arterial stiffness with resultant increase in afterload is not well known. We hypothesized that the aortic stiffness is higher in pediatric Fontan patients when compared to healthy controls. A prospective study was conducted at the Children's Hospital of Michigan. Twenty-two Fontan patients (aged 6-21 years) were compared with 22 healthy controls (aged 9-17 years) selected from children referred to our clinic who had normal cardiac anatomy and function on the echocardiogram. Aortic stiffness was assessed noninvasively by measuring the aortic augmentation index (AAI) using applanation tonometry (Sphygmocor, Atcor, IL). AAI was calculated as AP/PP where augmentation pressure (AP) is the increase in aortic systolic blood pressure (BP) and pulse pressure (PP) is the difference between aortic systolic and diastolic BP. Ten patients (45 %) had hypoplastic left ventricle, and 11 (50 %) had undergone aortic arch surgery. The median AAI was significantly higher in Fontan patients when compared to controls (12.5, IQR 4.8, 17.3 vs 0, IQR -6.3, 5.8; p = 0.0003). History of aortic arch surgery and single ventricle morphology did not have a significant impact on AAI. Pediatric patients who undergo Fontan palliation have significantly higher AAI, a marker of aortic stiffness and increased afterload, compared to healthy controls. Larger longitudinal studies are warranted to elucidate the possible contribution of elevated AAI on pump failure in these patients. PMID:25832849

  20. [Unicuspid Aortic Valve Stenosis Combined with Aortic Coarctation;Report of a Case].

    PubMed

    Kubota, Takehiro; Wakasa, Satoru; Shingu, Yasushige; Matsui, Yoshiro

    2016-06-01

    Unicuspid aortic valve in an adult is extremely rare. In addition, 90% of the patients with aortic coarctation are reported to die before the age 50. A 60-year-old woman was admitted to our hospital for further examination of exertional dyspnea which had begun one year before. She had been under medical treatment for hypertension since early thirties, and had been also diagnosed with moderate aortic stenosis at 50 years of age. She was at 1st diagnosed with aortic coarctation combined with bicuspid aortic valve stenosis. The aortic valve was then found unicuspid and was replaced under cardiopulmonary bypass with perfusion to both the ascending aorta and the femoral artery. Repair of aortic coarctation was performed 3 months later through left thoracotomy without extracorporeal circulation due to the rich collateral circulation. She had no postoperative complications, and hypertension as well as ankle-brachial index improved to the normal levels. PMID:27246132

  1. Rheumatic aortic stenosis in young patients presenting with combined aortic and mitral stenosis.

    PubMed Central

    Vijayaraghavan, G; Cherian, G; Krishnaswami, S; SUKUMAR, I P; John, S

    1977-01-01

    This report describes 30 patients under the age of 30 years with rheumatic aortic stenosis, presenting with combined aortic and mitral stenosis. Three patients had additional tricuspid stenosis. Twenty-eight patients gave a history of rheumatic polyarthritis. The diagnosis was confirmed by right and left heart catheterisation in all. The murmur of aortic stenosis was not initially present in 8 out of 10 patients in congestive heart failure. Aortic valve calcification was not seen. Cineangiography showed a tricuspid aortic valve in all, unlike congenital aortic stenosis. A unique feature of this group was the raised pulmonary vascular resistance in 87 per cent of the patients. The present study shows that patients in India developing aortic stenosis after rheumatic fever do so early in the natural history of the disease. PMID:849390

  2. Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

    PubMed Central

    Roccabianca, Sara; Ateshian, Gerard A.; Humphrey, Jay D.

    2013-01-01

    Spontaneous dissection of the human thoracic aorta is responsible for significant morbidity and mortality, yet this devastating biomechanical failure process remains poorly understood. In this paper, we present finite element simulations that support a new hypothesis for the initiation of aortic dissections that is motivated by extensive histopathological observations. Specifically, our parametric simulations show that the pooling of glycosaminoglycans/proteoglycans that is singularly characteristic of the compromised thoracic aorta in aneurysms and dissections can lead to significant stress concentrations and intra-lamellar Donnan swelling pressures. We submit that these localized increases in intramural stress may be sufficient both to disrupt the normal cell-matrix interactions that are fundamental to aortic homeostasis and to delaminate the layered microstructure of the aortic wall and thereby initiate dissection. Hence, pathologic pooling of glycosaminoglycans/proteoglycans within the medial layer of the thoracic aortic should be considered as a possible target for clinical intervention. PMID:23494585

  3. Novel mechanisms of abdominal aortic aneurysms.

    PubMed

    Lu, Hong; Rateri, Debra L; Bruemmer, Dennis; Cassis, Lisa A; Daugherty, Alan

    2012-10-01

    Abdominal aortic aneurysms (AAAs) are a common but asymptomatic disease that has high susceptibility to rupture. Current therapeutic options are limited to surgical procedures because no pharmacological approaches have been proven to decrease either expansion or rupture of human AAAs. The current dearth of effective medical treatment is attributed to insufficient understanding of the mechanisms underlying the initiation, propagation and rupture of AAAs. This review will emphasize recent advances in mechanistic studies that may provide insights into potential pharmacological treatments for this disease. While we primarily focus on recent salient findings, we also discuss mechanisms that continue to be controversial depending on models under study. Despite the progress on exploring mechanisms of experimental AAAs, ultimate validation of mechanisms will require completion of prospective double-blinded clinical trials. In addition, we advocate increased emphasis of collaborative studies using animal models and human tissues for determination of mechanisms that explore expansion and rupture of existing AAAs. PMID:22833280

  4. Abdominal aortic aneurysm--the forgotten diagnosis?

    PubMed Central

    Contini, S.; McMaster, P.

    1980-01-01

    A review of all cases of abdominal aortic aneurysm presenting to Addenbrooke's Hospital, Cambridge, in a 4-year period revealed that there were 118 such patients and confirmed the relatively low operative mortality for elective aneurysmal surgery (6.6%) compared with the high mortality (66.6%) for ruptured or leaking abdominal aneurysm. In only 50% of the cases was the correct diagnosis made during the lifetime of the patient; nor was the correct diagnosis always made after admission to hospital. The need for an early and accurate diagnosis of abdominal aneurysms is stressed and an increased awareness of this condition, based on well established clinical features, would undoubtedly reduce the overall mortality. Images Fig. 1 PMID:7393787

  5. 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

  6. Changing strategy for aortic stenosis with coronary artery disease by transcatheter aortic valve implantation.

    PubMed

    Kobayashi, Junjiro

    2013-12-01

    Coronary artery disease (CAD) is combined with aortic stenosis (AS) in 40-50 % of patients with typical angina. Recently, transcatheter aortic valve implantation (TAVI) has changed the guideline for AS in patients with high comorbidity. At the same time more than 60 % of isolated CABG has been performed without cardiopulmonary bypass in Japan. CABG is recommended and should be considered in patients with primary indication for AVR and luminal stenosis >70 % in major coronary arteries and the left internal thoracic artery (LITA) by guidelines. AVR is indicated for severe AS undergoing CABG. It is generally accepted to perform AVR for moderate AS at the time of CABG by valve guidelines. However, prophylactic AVR for moderate AS associated with CABG may increase the early operative risk and expose the patients to postoperative long-term valve related complications. AVR after previous CABG poses potential risk for mortality and morbidity. The presence of patent ITA is a significant risk of its injury and difficulty of myocardial protection during aortic cross-clamping. Therefore, at present, for severe AS previous CABG with patent ITA should be one of the definite indications of TAVI. Rationale of TAVI in patients with severe AS and CAD has not been clearly delineated. The safety of TAVI irrespective of the extent and anatomy of CAD is still controversial. PCI is not appropriate before TAVI in high-risk patients with CAD. In the near future hybrid TAVI will be realistic considering least operative mortality and morbidity in high-risk patients. PMID:23546769

  7. Mitral and aortic regurgitation following transcatheter aortic valve replacement

    PubMed Central

    Szymański, Piotr; Hryniewiecki, Tomasz; Dąbrowski, Maciej; Sorysz, Danuta; Kochman, Janusz; Jastrzębski, Jan; Kukulski, Tomasz; Zembala, Marian

    2016-01-01

    Objective To analyse the impact of postprocedural mitral regurgitation (MR), in an interaction with aortic regurgitation (AR), on mortality following transcatheter aortic valve implantation (TAVI). Methods To assess the interaction between MR and AR, we compared the survival rate of patients (i) without both significant MR and AR versus (ii) those with either significant MR or significant AR versus (iii) with significant MR and AR, all postprocedure. 381 participants of the Polish Transcatheter Aortic Valve Implantation Registry (166 males (43.6%) and 215 females (56.4%), age 78.8±7.4 years) were analysed. Follow-up was 94.1±96.5 days. Results Inhospital and midterm mortality were 6.6% and 10.2%, respectively. Significant MR and AR were present in 16% and 8.1% patients, including 3.1% patients with both significant MR and AR. Patients with significant versus insignificant AR differed with respect to mortality (log rank p=0.009). This difference was not apparent in a subgroup of patients without significant MR (log rank p=0.80). In a subgroup of patients without significant AR, there were no significant differences in mortality between individuals with versus without significant MR (log rank p=0.44). Significant MR and AR had a significant impact on mortality only when associated with each other (log rank p<0.0001). At multivariate Cox regression modelling concomitant significant MR and AR were independently associated with mortality (OR 3.2, 95% CI 1.54 to 5.71, p=0.002). Conclusions Significant MR or AR postprocedure, when isolated, had no impact on survival. Combined MR and AR had a significant impact on a patient's prognosis. PMID:26908096

  8. Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation

    PubMed Central

    Zhong, Xing; Xiu, Ling-ling; Wei, Guo-hong; Liu, Yuan-yuan; Su, Lei; Cao, Xiao-pei; Li, Yan-bing; Xiao, Hai-peng

    2011-01-01

    Aim: To investigate the effects of bezafibrate on the proliferation and differentiation of osteoblastic MC3T3-E1 cells, and to determine the signaling pathway underlying the effects. Methods: MC3T3-E1 cells, a mouse osteoblastic cell line, were used. Cell viability and proliferation were examined using MTT assay and colorimetric BrdU incorporation assay, respectively. NO production was evaluated using the Griess reagent. The mRNA expression of ALP, collagen I, osteocalcin, BMP-2, and Runx-2 was measured using real-time PCR. Western blot analysis was used to detect the expression of AMPK and eNOS proteins. Results: Bezafibrate increased the viability and proliferation of MC3T3-E1 cells in a dose- and time-dependent manner. Bezafibrate (100 μmol/L) significantly enhanced osteoblastic mineralization and expression of the differentiation markers ALP, collagen I and osteocalcin. Bezafibrate (100 μmol/L) increased phosphorylation of AMPK and eNOS, which led to an increase of NO production by 4.08-fold, and upregulating BMP-2 and Runx-2 mRNA expression. These effects could be blocked by AMPK inhibitor compound C (5 μmol/L), or the PPARβ inhibitor GSK0660 (0.5 μmol/L), but not by the PPARα inhibitor MK886 (10 μmol/L). Furthermore, GSK0660, compound C, or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mmol/L) could reverse the stimulatory effects of bezafibrate (100 μmol/L) on osteoblast proliferation and differentiation, whereas MK886 only inhibited bezafibrate-induced osteoblast proliferation. Conclusion: Bezafibrate stimulates proliferation and differentiation of MC3T3-E1 cells, mainly via a PPARβ-dependent mechanism. The drug might be beneficial for osteoporosis by promoting bone formation. PMID:21499286

  9. 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

  10. 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

  11. MRI evaluation prior to Transcatheter Aortic Valve Implantation (TAVI): When to acquire and how to interpret.

    PubMed

    Chaturvedi, Abhishek; Hobbs, Susan K; Ling, Fred S; Chaturvedi, Apeksha; Knight, Peter

    2016-04-01

    Transcatheter Aortic Valve Implantation (TAVI) is increasingly being used in patients with severe aortic stenosis who are not candidates for surgery. ECG-gated CT angiography (CTA) plays an important role in the preoperative planning for these devices. As the number of patients undergoing these procedures increases, a subset of patients is being recognized who have contraindications to iodinated contrast medium, either due to a prior severe allergic type reaction or poor renal function. Another subgroup of patients with low flow and low gradient aortic stenosis is being recognized that are usually assessed for severity of aortic stenosis by stress echocardiography. There are contraindications to stress echocardiography and some of these patients may not be able to undergo this test. Non-contrast MRI can be a useful emerging modality for evaluating these patients. In this article, we discuss the emerging indications of non-contrast MRI in preoperative assessment for TAVI and describe the commonly used MRI sequences. A comparison of the most important measurements obtained for TAVI assessment on CTA and MRI from same subjects is included. Teaching Points • MRI can be used for preoperative assessment of aortic annulus. • MRI is an alternate to CTA when iodinated contrast is contraindicated. • Measurements obtained by non-contrast MRI are similar to contrast enhanced CTA. • MRI can be used to assess severity of aortic stenosis. PMID:26911969

  12. In vitro proliferation of aortic smooth muscle cells from spontaneously hypertensive and normotensive rats.

    PubMed

    Pang, S C

    1989-06-01

    The characteristics and proliferation of aortic smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied in culture. Smooth muscle cells were isolated from the tunica media of the thoracic aorta by an explant method. Immunofluorescence microscopy showed that 93-95 per cent of cells were positively labelled with antibodies raised against smooth muscle actin, indicating that these were smooth muscle cells. The proliferative activity was compared between aortic smooth muscle cells from hypertensive and normotensive rats in culture by thymidine incorporation and cell number determinations. The results demonstrate that aortic smooth muscle cells from hypertensive rats grew faster than those from normotensive rats in culture. The increased proliferative activity of cultured aortic smooth muscle cells from hypertensive rats was detectable even when they were cultured in a chemically defined serum-free medium. These data have shown that an increased proliferative activity of aortic smooth muscle cells from hypertensive rats can occur in culture conditions without the influence of arterial pressure or other stimuli as in intact animals. The mechanisms underlying the accelerated proliferative activity of aortic smooth muscle cells from genetically hypertensive rats in vitro remain to be determined. PMID:2754547

  13. Intraoperative tracking of aortic valve plane.

    PubMed

    Nguyen, D L H; Garreau, M; Auffret, V; Le Breton, H; Verhoye, J P; Haigron, P

    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

  14. Acute aortic dissection in pregnant women.

    PubMed

    Yang, Zhaohua; Yang, Shouguo; Wang, Fangshun; Wang, Chunsheng

    2016-05-01

    Acute aortic dissection occurring during pregnancy represents a lethal risk to both the mother and fetus. Management of parturient with acute aortic dissection is complex. We report our experience of two pregnancies with type A acute aortic dissection. One patient is a 31-year-old pregnant woman (33rd gestational week) with a bicuspid aortic valve and the other is a 32-year-old pregnant woman (30th gestational week) with the Marfan syndrome. In both cases, a combined emergency operation consisting of Cesarean section, total hysterectomy prior to corrective surgery for aortic dissection was successfully performed within a relatively short period of time after the onset. Both patients' postoperative recovery was uneventful, and we achieved a favorable maternal and fetal outcome. PMID:25085319

  15. 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

  16. [Correlation between electrocardiographic and echocardiographic findings in chronic aortic insufficiency].

    PubMed

    Di Bello, V; Salvatore, L; Paolini, G; Lunardi, M; Cini, G; Rossi, M; Santoro, G; Galetta, F; Adami, P; Pentimone, F

    1984-12-01

    Echocardiographic indices of left ventricular volume and mass and electrocardiographic indices of left ventricular hypertrophy have evaluated in 25 patients with chronic aortic regurgitation and in 10 normal subjects. When the patients with aortic regurgitation were subdivided in three groups with increasing evidence of left ventricular hypertrophy, the echocardiographic measures of left ventricular dimension and mass were also found to be increased, with statistically significant differences between patients and controls and among the three groups of patients as well. A specially constructed cumulative electrocardiographic index of left ventricular hypertrophy (Sokolow and Lyon's index plus Lewis' index plus strain pattern) is correlated with the left ventricular end-diastolic diameter (r = 0.65; P less than 0.001), cross-sectional area (r = 0.65; p less than 0.001) and mass (r = 0.75; p less than 0.001) better than the isolated electrocardiographic indexes. PMID:6241910

  17. Convex ENO High Order Multi-dimensional Schemes without Field by Field Decomposition or Staggered Grids

    NASA Astrophysics Data System (ADS)

    Liu, Xu-Dong; Osher, Stanley

    1998-05-01

    Second order accurate (first order at extrema) cell averaged based approximations extending the Lax-Friedrichs central scheme, using component-wise rather than field-by-field limiting, have been found to give surprisingly good results for a wide class of problems involving shocks (see H. Nessyahu and E. Tadmor, J. Comput. Phys.87, 408, 1990). The advantages of component-wise limiting compared to its counterpart, field-by-field limiting, are apparent: (1) No complete set of eigenvectors is needed and hence weakly hyperbolic systems can be solved. (2) Component-wise limiting is faster than field-by-field limiting. (3) The programming is much simpler, especially for complicated coupled systems of many equations. However, these methods are based on cell-averages in a staggered grid and are thus a bit complicated to extend to multiple dimensions. Moreover the staggering causes slight difficulties at the boundaries. In this work we modify and extend this component-wise central differencing based procedure in two directions: (1) Point values, rather than cell averages are used, thus removing the need for staggered grids, and also making the extension to multi-dimensions quite simple. We use TVD Runge-Kutta time discretizations to update the solution. (2) A new type of decision process, which follows the general ENO philosophy is introduced and used. This procedure enables us to extend our method to a third order component-wise central ENO scheme, which apparently works well and is quite simple to implement in multi-dimensions. Additionally, our numerical viscosity is governed by the local magnitude of the maximum eigenvalue of the Jacobian, thus reducing the smearing in the numerical results. We found a speed up of a factor of 2 in each space dimension, on a SGI O2workstation, over methods based on field-by-field decomposition limiting. The new decision process leads to new, "convex" ENO schemes which, we believe, are of interest in a more general setting. Our numerical

  18. Wall stretch and thromboxane A2 activate NO synthase (eNOS) in pulmonary arterial smooth muscle cells via H2O2 and Akt-dependent phosphorylation.

    PubMed

    Kim, Hae Jin; Yoo, Hae Young; Jang, Ji Hyun; Lin, Hai Yue; Seo, Eun Yeong; Zhang, Yin Hua; Kim, Sung Joon

    2016-04-01

    Pulmonary arteries (PAs) have high compliance, buffering the wide ranges of blood flow. Here, we addressed a hypothesis that PA smooth muscle cells (PASMCs) express nitric oxide synthases (NOS) that might be activated by mechanical stress and vasoactive agonists. In the myograph study of endothelium-denuded rat PAs, NOS inhibition (L-NAME) induced strong contraction (96 % of 80 mM KCl-induced contraction (80K)) in the presence of 5 nM U46619 (thromboxane A2 (TXA2) analogue) with relatively high basal stretch (2.94 mN, S(+)). With lower basal stretch (0.98 mN, S(-)), however, L-NAME application following U46619 (TXA2/L-NAME) induced weak contraction (27 % of 80K). Inhibitors of nNOS and iNOS had no such effect in S(+) PAs. In endothelium-denuded S(+) mesenteric and renal arteries, TXA2/L-NAME-induced contraction was only 18 and 21 % of 80K, respectively. Expression of endothelial-type NOS (eNOS) in rat PASMCs was confirmed by RT-PCR and immunohistochemistry. Even in S(-) PAs, pretreatment with H2O2 (0.1-10 μM) effectively increased the sensitivity to TXA2/L-NAME (105 % of 80K). Vice versa, NADPH oxidase inhibitors, reactive oxygen species scavengers, or an Akt inhibitor (SC-66) suppressed TXA2/L-NAME-induced contraction in S(+) PAs. In a human PASMC line, immunoblot analysis showed the following: (1) eNOS expression, (2) Ser(1177) phosphorylation by U46619 and H2O2, and (3) Akt activation (Ser(473) phosphorylation) by U46619. In the cell-attached patch clamp study, H2O2 facilitated membrane stretch-activated cation channels in rat PASMCs. Taken together, the muscular eNOS in PAs can be activated by TXA2 and mechanical stress via H2O2 and Akt-mediated signaling, which may counterbalance the contractile signals from TXA2 and mechanical stimuli. PMID:26729266

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. High-order ENO methods for the unsteady compressible Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Atkins, H. L.

    1991-01-01

    The adaptive stencil concepts of ENO (Essentially Non-Oscillatory) methods are applied to the laminar Navier-Stokes equations to yield a high-order, time-accurate algorithm with a shock-capturing capability. The method targets problems in the areas of nonlinear acoustics, compressible transition, and turbulence which, due to the presence of shocks or complex geometries, are not easily solved by spectral methods. The present approach has been implemented and tested for the full three-dimensional Navier-Stokes equations in a transformed curvilinear coordinate system. Validation results are presented for a variety of problems which verify the method's accuracy properties and shock capturing capabilities, as well as demonstrate its use as a direct simulation tool.

  4. 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

  5. COX2 Inhibition Reduces Aortic Valve Calcification In Vivo

    PubMed Central

    Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E.

    2016-01-01

    Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432

  6. 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 primarily by age-related degeneration and progressive calcification typically detected in patients 65 years and older. In patients presenting with symptoms of heart failure, the average survival rate is only 2 years without appropriate treatment. Approximately one half of all patients die within the first 2 to 3 years of symptom onset. In addition, the age of the patients presenting for aortic valve replacement (AVR) is increased along with the demographic changes. The Society of Thoracic Surgeons (STS) database shows that the number of patients older than 80 years has increased from 12% to 24% during the past 20 years. At the same time, the percentage of candidates requiring AVR as well as concomitant coronary bypass surgery has increased from 5% to 25%. Surgical AVR continues to be the criterion standard for treatment of aortic stenosis, improving survival and quality of life. Recent advances in prosthetic valve technology, such as transcatheter AVR, have expanded the indication for AVR to the extreme high-risk population, and the most recent surgical innovation, rapid deployment AVR, provides an additional tool to the surgeons’ armamentarium. PMID:26918310

  7. A high-order symmetrical weighted hybrid ENO-flux limiter scheme for hyperbolic conservation laws

    NASA Astrophysics Data System (ADS)

    Abedian, Rooholah; Adibi, Hojatollah; Dehghan, Mehdi

    2014-01-01

    In this paper, we propose a new weighted essentially non-oscillatory (WENO) procedure for solving hyperbolic conservation laws, on uniform meshes. The new scheme combines essentially non-oscillatory (ENO) reconstructions together with monotone upwind schemes for scalar conservation laws' interpolants. In a one-dimensional context, first, we obtain an optimum polynomial on a five-cells stencil. This optimum polynomial is fifth-order accurate in regions of smoothness. Next, we modify a third-order ENO polynomial by choosing an additional point inside the stencil in order to obtain the highest accuracy when combined with the Harten-Osher reconstruction-evolution method limiter. Then, we consider the optimum polynomial as a symmetric and convex combination of four polynomials with ideal weights. After that, following the methodology of the classic WENO procedure, we calculate non-oscillatory weights with the ideal weights. Also, the numerical solution is advanced in time by means of the linear multi-step total variation bounded (TV B) technique. Numerical examples on both scalar and gas dynamics problems confirm that the new scheme is non-oscillatory and yields sharp results when solving profiles with discontinuities. Comparing the new scheme with high-order WENO schemes shows that our method reduces smearing near shocks and corners, and in some cases it is more accurate near discontinuities. Finally, the new method is extended to multi-dimensional problems by a dimension-by-dimension approach. Several multi-dimensional examples are performed to show that our method remains non-oscillatory while giving good resolution of discontinuities.

  8. Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy.

    PubMed

    Luizon, Marcelo R; Sandrim, Valeria C; Palei, Ana Ct; Lacchini, Riccardo; Cavalli, Ricardo C; Duarte, Geraldo; Tanus-Santos, Jose E

    2012-09-01

    Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)₁₃-₂₅, rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. PMID:22573202

  9. Aortic dissection and sport: physiologic and clinical understanding provide an opportunity to save young lives.

    PubMed

    Mayerick, C; Carré, F; Elefteriades, J

    2010-10-01

    Understanding the relationship between acute type A aortic dissection and sport is crucial to prevent sudden cardiac death in seemingly healthy young individuals. Aerobic exercise produces only a modest rise in arterial blood pressure (140-160 mmHg) except at the highest levels of exertion, at which pressures between 180-220 mmHg are reached. Weight training, on the other hand, routinely produces acute rises in blood pressure to over 300 mmHg. This presents a danger for individuals with an unknown aortic aneurysm; the deteriorated mechanical properties of the aortic wall resulting from aneurysmal enlargement increase the susceptibility to aortic rupture when the high wall coincident with exertion exceeds the tensile strength of the aortic wall. Investigations by our group into the inciting events leading up to dissection have demonstrated a causal link between extreme exertion, severe emotional stress, and acute type A aortic dissection. Since aortic enlargement is often unknown to persons participating in weight training, especially in the youth population, a ìSnapShot Echocardiogramî screening program is been proposed; such a pilot program will raise awareness of the importance of pre-participation cardiac screening and allow for early detection of aneurysms as a means of preventing this ìsilent killerî from striking. As strong supporters of the numerous benefits of weight training, we encourage this activity in individuals without aneurysm; without aneurysm, wall tension does not reach dangerous levels, even at extremes of exertion. For individuals with known aortic dilatation, we recommend a program that limits their lifting to 50% of body weight in the bench press or equivalent level of perceived exertion for other specific strength exercises. PMID:20924328

  10. eNOS3 Genetic Polymorphism Is Related to Post-Ablation Early Recurrence of Atrial Fibrillation

    PubMed Central

    Shim, Jaemin; Park, Jae Hyung; Lee, Ji-Young; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Ellinor, Patrick T.

    2015-01-01

    Purpose Previous studies have demonstrated an association between eNOS polymorphisms and atrial fibrillation (AF). We sought to determine whether eNOS polymorphisms are associated with AF recurrence after a radiofrequency catheter ablation (RFCA). Materials and Methods A total of 500 consecutive patients (56±11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA and 500 age, gender-matched controls were genotyped for the eNOS3 single nucleotide polymorphism (rs1799983). AF recurrence was monitored according to 2012 ACC/AHA/ESC guidelines. Results The frequencies of the rs1799983 variant alleles (T) in the case and control group were not significantly different (OR 1.05, 95% CI 0.75-1.46, p=0.798). AF patients with rs1799983 variants were more likely to have coronary artery disease or stroke than those without genetic variant at this gene (31.0% vs. 17.3%, p=0.004). During mean 17 months follow-up, early recurrence of AF (ERAF; within 3 months) and clinical recurrence (CR) of AF were 31.8% and 24.8%, respectively. The rs1799983 variant was associated with higher risk of ERAF (OR 1.71, 95% CI 1.06-2.79, p=0.028), but not with CR. ERAF occurred earlier (11±16 days) in variant group than those without variant allele (20±25 days, p=0.016). A multiple logistic regression analysis showed that presence of the rs1799983 variant (OR 1.75, 95% CI 1.07-2.86, p=0.026) and persistent AF were independent predictors for ERAF after AF ablation. Conclusion The rs1799983 variant of the eNOS3 gene was associated with ERAF, but not with CR, after RFCA. eNOS3 gene variants may have a potential role for stratification of post-ablation management. PMID:26256966

  11. iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease

    PubMed Central

    Martin-Rojas, Tatiana; Mourino-Alvarez, Laura; Alonso-Orgaz, Sergio; Rosello-Lleti, Esther; Calvo, Enrique; Lopez-Almodovar, Luis Fernando; Rivera, Miguel; Padial, Luis R.; Lopez, Juan Antonio; Cuesta, Fernando de la; Barderas, Maria G.

    2015-01-01

    Degenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development. PMID:26620461

  12. Aortic dissection with the entrance tear in transverse aorta: analysis of 12 autopsy patients.

    PubMed

    Roberts, C S; Roberts, W C

    1990-11-01

    Clinical and autopsy findings are described in 12 patients who had fatal aortic dissection with the entrance tear in the transverse aorta. The 12 patients represent 7% of 182 autopsies of spontaneous aortic dissection studied by us. The ages of the 12 patients at death ranged from 37 to 87 years (mean, 67 years). Eight were men; 8 had a history of systemic hypertension, and 10 had hearts of increased weight. Diagnosis of aortic dissection was made during life in only 4 of the 12 patients. All 12 patients died of rupture of the false channel within 2 weeks of onset of signs or symptoms compatible with dissection. The direction of aortic dissection from the entrance tear was entirely retrograde in 4 patients, entirely anterograde in 4 patients, and in both directions in 4 patients. Hemopericardium occurred in the first group, left hemothorax in the second group, and either in the last group. Of the 8 patients in whom the ascending aorta was involved, the retrograde dissection in each extended to the aortic root, 6 had pulmonary adventitial hemorrhage, and 4 had involvement of the arch arteries by dissection. In the 4 patients with strictly anterograde dissection, none had dissection in the arch arteries. Thus, tear in the transverse aorta causes a dissection that is usually fata, that often dissects retrogradely, and that may mimic dissection from a tear in ascending aorta. Aortic dissection from a tear in transverse aorta requires early operative intervention. PMID:2241339

  13. Quadricuspid aortic valve with ruptured sinus of Valsalva.

    PubMed

    Akerem Khan, Shamruz Khan; Tamin, Syahidah Syed; Burkhart, Harold M; Araoz, Philip A; Young, Phillip M

    2013-02-01

    We present a case of a 24-year-old woman who was diagnosed with quadricuspid aortic valve with ruptured sinus of Valsalva. Quadricuspid aortic valve is a rare congenital cardiac anomaly. The recognition of quadricuspid aortic valve has clinical significance as it causes aortic valve dysfunction, and is often associated with other congenital cardiac abnormalities. We showed the important role of multimodality imaging in diagnosing a quadricuspid aortic valve associated with ruptured sinus of Valsalva. PMID:22874066

  14. Aortic valve allografts in sheep

    PubMed Central

    Borrie, John; Hill, G. L.

    1968-01-01

    Some of the mechnical and biological problems surrounding the use of fresh allograft inverted aortic valves as mitral valve substitutes are described. Certain aspects of the problem have been studied experimentally. In three sheep `fresh' aortic valve allografts were inserted, using cardiopulmonary bypass, into the main pulmonary artery, and were observed from 5 to 7 months after operation. The animals survived normally. Their normal pulmonary valves remained in situ. The technique is described. At subsequent necropsy, macroscopically the valves were found to be free from vegetation, and the cusps were pliable and apparently normal. Microscopically, the supporting allograft myocardium showed necrosis and early calcification. The valve cusp showed hyalinization of collagen, although beneath the endocardium this hyalinized collagen contained moderate numbers of fibroblasts with no evidence of proliferation. The endocardium and arterial intima of the allograft showed evidence of ingrowth from adjacent normal host endocardial tissues. The allograft itself was invested in a loose layer of fibro-fatty tissue, which, in view of the necrotic state of the graft myocardium, could well have been a reparative reaction rather than a homograft reaction. It is concluded that, although the cusps could function normally, the necrosis of the myocardium might in time lead to late failure of the graft. Further studies with the valve inserted at mitral level are indicated. Images PMID:5656757

  15. Thrombus Volume Change Visualization after Endovascular Abdominal Aortic Aneurysm Repair

    NASA Astrophysics Data System (ADS)

    Maiora, Josu; García, Guillermo; Macía, Iván; Legarreta, Jon Haitz; Boto, Fernando; Paloc, Céline; Graña, Manuel; Abuín, Javier Sanchez

    A surgical technique currently used in the treatment of Abdominal Aortic Aneurysms (AAA) is the Endovascular Aneurysm Repair (EVAR). This minimally invasive procedure involves inserting a prosthesis in the aortic vessel that excludes the aneurysm from the bloodstream. The stent, once in place acts as a false lumen for the blood current to travel down, and not into the surrounding aneurysm sac. This procedure, therefore, immediately takes the pressure off the aneurysm, which thromboses itself after some time. Nevertheless, in a long term perspective, different complications such as prosthesis displacement or bloodstream leaks into or from the aneurysmatic bulge (endoleaks) could appear causing a pressure elevation and, as a result, increasing the danger of rupture. The purpose of this work is to explore the application of image registration techniques to the visual detection of changes in the thrombus in order to assess the evolution of the aneurysm. Prior to registration, both the lumen and the thrombus are segmented

  16. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

    PubMed Central

    Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca

    2015-01-01

    The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases. PMID:26426360

  17. Aortic Stenosis and Vascular Calcifications in Alkaptonuria

    PubMed Central

    Hannoush, Hwaida; Introne, Wendy J.; Chen, Marcus Y.; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A.; Gahl, William A.; Sachdev, Vandana

    2011-01-01

    Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. PMID:22100375

  18. The Effects of Positioning of Transcatheter Aortic Valve on Fluid Dynamics of the Aortic Root

    PubMed Central

    Su, Jimmy L; Kheradvar, Arash

    2015-01-01

    Transcatheter aortic valve implantation is a novel treatment for severe aortic valve stenosis. Due to the recent use of this technology and the procedural variability, there is very little data that quantifies the hemodynamic consequences of variations in valve placement. Changes in aortic wall stresses and fluid retention in the sinuses of Valsalva can have a significant effect on the clinical response a patient has to the procedure. By comprehensively characterizing complex flow in the sinuses of Valsalva using Digital Particle Image Velocimetry and an advanced heart flow simulator, various positions of a deployed transcatheter valve with respect to a bioprosthetic aortic valve (valve-in-valve) were tested in vitro. Displacements of the transcatheter valve were axial and directed below the simulated native valve annulus. It was determined that for both blood residence time and aortic Reynolds stresses, it is optimal to have the annulus of the transcatheter valve deployed as close to the aortic valve annulus as possible. PMID:25010918

  19. Balloon aortic valvuloplasty as a treatment option in the era of transcatheter aortic valve implantation.

    PubMed

    Costopoulos, Charis; Sutaria, Nilesh; Ariff, Ben; Fertleman, Michael; Malik, Iqbal; Mikhail, Ghada W

    2015-05-01

    Aortic valve stenosis is the commonest encountered valvular pathology and a frequent cause of morbidity and mortality in cases of severe stenosis. Definitive treatment has traditionally been offered in the form of surgical aortic valve replacement in patients with an acceptable surgical risk and more recently with the less invasive transcatheter aortic valve implantation (TAVI) in those where surgery is not a viable option. Prior to the introduction of TAVI, inoperable patients were treated medically and where appropriate with balloon aortic valvuloplasty, a procedure which although effective only provided short-term relief and was associated with high complication rates especially during its infancy. Here we discuss whether balloon aortic valvuloplasty continues to have a role in contemporary clinical practice in an era where significant advances have been achieved in the fields of surgical aortic valve replacement, TAVI and postoperative care. PMID:25865236

  20. Abdominal aortic aneurysm and histological, clinical, radiological correlation.

    PubMed

    Rodella, Luigi Fabrizio; Rezzani, Rita; Bonomini, Francesca; Peroni, Michele; Cocchi, Marco Angelo; Hirtler, Lena; Bonardelli, Stefano

    2016-04-01

    To date, the pathogenesis of abdominal aortic aneurism (AAA) still remains unclear. As such, the aim of this study was to evaluate changes of the aortic structure during AAA. We analysed the microscopic frame of vessels sections, starting from the primum movens leading to abnormal dilatation. AAA samples were collected and processed through various staining methods (Verhoeff-Van Gieson, Masson Goldner, Sirius Red). Subsequently, the vessel morphology and collagenic web of the tunica media and adventitia were determined and the amount of type I and type III collagen was measured. We also applied immune-histochemistry markers for CD34 and PGP 9.5 in order to identify vascular and nerve structures in the aorta. Immune-positivity quantification was used to calculate the percentage of the stained area. We found increasing deposition of type I collagen and reduced type III collagen in both tunica media and adventitia of AAA. The total amount of vasa vasorum, marked with CD34, and nerva vasorum, marked with PGP 9.5, was also higher in AAA samples. Cardiovascular risk factors (blood pressure, dyslipidemia, cigarette smoking) and radiological data (maximum aneurism diameter, intra-luminal thrombus, aortic wall calcification) increased these changes. These results suggest that the tunica adventitia may have a central role in the pathogenesis of AAA as clearly there are major changes characterized by rooted inflammatory infiltration. The presence of immune components could explain these modifications within the framework of the aorta. PMID:26858185

  1. Circulating CD14+ monocytes in patients with aortic stenosis

    PubMed Central

    Shimoni, Sara; Meledin, Valery; Bar, Iris; Fabricant, Jacob; Gandelman, Gera; George, Jacob

    2016-01-01

    Background Calcific aortic stenosis (AS) is an active process sharing similarities with atherosclerosis and chronic inflammation. The pathophysiology of AS is notable for three cardinal components: inflammation, fibrosis and calcification. Monocytes play a role in each of these processes. The role of circulating monocytes in AS is not clear. The aim of the present study was to study an association between circulating apoptotic and non apoptotic CD14+ monocytes and AS features. Methods We assessed the number of CD14+ monocytes and apoptotic monocytes in 54 patients with significant AS (aortic valve area 0.74 ± 0.27 cm2) and compared them to 33 patients with similar risk factors and no valvular disease. The level of CD14+ monocytes and apoptotic monocytes was assessed by flow cytometry. Results There was no difference in the risk factor profile and known coronary or peripheral vascular diseases between patients with AS and controls. Patients with AS exhibited increased numbers of CD14+ monocytes as compared to controls (9.9% ± 4.9% vs. 7.7% ± 3.9%, P = 0.03). CD14+ monocyte number was related to age and the presence and severity of AS. In patients with AS, both CD14+ monocytes and apoptotic monocytes were inversely related to aortic valve area. Conclusions Patients with significant AS have increased number of circulating CD14+ monocytes and there is an inverse correlation between monocyte count and aortic valve area. These findings may suggest that inflammation is operative not only in early valve injury phase, but also at later developed stages such as calcification when AS is severe. PMID:26918018

  2. Calcific aortic valve disease: A consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease

    PubMed Central

    Yutzey, Katherine E.; Demer, Linda L.; Body, Simon C.; Huggins, Gordon S.; Towler, Dwight A.; Giachelli, Cecilia M.; Hofmann-Bowman, Marion A.; Mortlock, Douglas P.; Rogers, Melissa B.; Sadeghi, Mehran M.; Aikawa, Elena

    2014-01-01

    Calcific Aortic Valve Disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis. This group identified CAVD as an actively regulated disease process in need of further study. As a result, the Alliance of Investigators on CAVD was formed to coordinate and promote CAVD research, with the goals of identifying individuals at risk, developing new therapeutic approaches, and improving diagnostic methods. The group is composed of cardiologists, geneticists, imaging specialists, and basic science researchers. This report reviews the current status of CAVD research and treatment strategies with identification of areas in need of additional investigation for optimal management of this patient population. PMID:25189570

  3. Management of Traumatic Aortic and Splenic Rupture in a Patient With Ascending Aortic Aneurysm.

    PubMed

    Topcu, Ahmet Can; Ciloglu, Ufuk; Bolukcu, Ahmet; Dagsali, Sabri

    2016-08-01

    Traumatic aortic rupture is rupture of all or part of the aortic wall, mostly resulting from blunt trauma to the chest. The most common site of rupture is the aortic isthmus. Traumatic rupture of the ascending aorta is rare. A 62-year-old man with a family history of ascending aortic aneurysm was referred to our hospital after a motor vehicle accident. He had symptoms of cardiogenic shock. A contrast-enhanced computed tomographic scan revealed rupture of the proximal ascending aorta and an ascending aortic aneurysm with a diameter of 55 mm at the level of the sinuses of Valsalva. Transthoracic echocardiography at the bedside revealed severe aortic valvular insufficiency. We performed a successful Bentall procedure. During postoperative recovery, the patient experienced a cerebrovascular accident. Transesophageal echocardiography did not reveal thrombosis of the mechanical prosthesis. The patient's symptoms resolved in time, and he was discharged from the hospital on postoperative day 47 without any sequelae. He has been symptom free during a 6-month follow-up period. We suggest that individuals who have experienced blunt trauma to the chest and have symptoms of traumatic aortic rupture and a known medical history of ascending aortic aneurysm should be evaluated for a rupture at the ascending aorta and the aortic isthmus. PMID:27449463

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

    PubMed

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

    2015-08-01

    Accurate Stroke Volume (SV) monitoring is essential for patient with cardiovascular dysfunction patients. However, direct SV measurements are not clinically feasible due to the highly invasive nature of measurement devices. Current devices for indirect monitoring of SV are shown to be inaccurate during sudden hemodynamic changes. This paper presents a novel SV estimation using readily available aortic pressure measurements and aortic cross sectional area, using data from a porcine experiment where medical interventions such as fluid replacement, dobutamine infusions, and recruitment maneuvers induced SV changes in a pig with circulatory shock. Measurement of left ventricular volume, proximal aortic pressure, and descending aortic pressure waveforms were made simultaneously during the experiment. From measured data, proximal aortic pressure was separated into reservoir and excess pressures. Beat-to-beat aortic characteristic impedance values were calculated using both aortic pressure measurements and an estimate of the aortic cross sectional area. SV was estimated using the calculated aortic characteristic impedance and excess component of the proximal aorta. The median difference between directly measured SV and estimated SV was -1.4ml with 95% limit of agreement +/- 6.6ml. This method demonstrates that SV can be accurately captured beat-to-beat during sudden changes in hemodynamic state. This novel SV estimation could enable improved cardiac and circulatory treatment in the critical care environment by titrating treatment to the effect on SV. PMID:26736434

  5. Liverpool Aortic Surgery Symposium V: New Frontiers in Aortic Disease and Surgery

    PubMed Central

    Bashir, Mohamad; Fok, Matthew; Shaw, Matthew; Field, Mark; Kuduvalli, Manoj; Desmond, Michael; Harrington, Deborah; Rashid, Abbas; Oo, Aung

    2014-01-01

    Aortic aneurysm disease is a complex condition that requires a multidisciplinary approach in management. The innovation and collaboration among vascular surgery, cardiothoracic surgery, interventional radiology, and other related specialties is essential for progress in the management of aortic aneurysms. The Fifth Liverpool Aortic Surgery Symposium that was held in May 2013 aimed at bringing national and international experts from across the United Kingdom and the globe to deliver their thoughts, applications, and advances in aortic and vascular surgery. In this report, we present a selected short synopsis of the key topics presented at this symposium. PMID:26798724

  6. Hybrid Thoracic Endovascular Aortic Repair for Intercostal Patch Aneurysm after Thoracoabdominal Aortic Replacement

    PubMed Central

    Yoshitake, Akihiro; Hachiya, Takashi; Okamoto, Kazuma; Hirano, Akinori; Kasai, Mio; Akamatsu, Yuta; Oka, Hidetoshi; Shimizu, Hideyuki

    2015-01-01

    We report a case of hybrid thoracic endovascular aortic repair for intercostal patch aneurysm after thoracoabdominal aortic replacement. Eighteen years ago, a 63-year-old woman with Marfan syndrome had undergone thoracoabdominal aortic replacement with reimplantation of the intercostal artery in an island fashion. Follow-up computed tomography (CT) revealed a remaining intercostal patch aneurysm of diameter 60 mm 17 years after the last operation. Hybrid thoracic endovascular aortic repair for exclusion of this intercostal patch aneurysm was successfully performed, with visceral artery bypasses. Postoperative CT showed no anastomotic stenosis or endoleak. PMID:26730265

  7. Consecutive transcatheter valve-in-valve implantations: the first in the aortic position, the second in the mitral position, in a patient with failing aortic and mitral bioprostheses

    PubMed Central

    Duncan, Alison; Davies, Simon; Rosendahl, Ulrich; Moat, Neil

    2014-01-01

    A 69-year-old man with a failing aortic valve homograft and failing mitral valve xenograft was admitted with an inability to complete full sentences and pulmonary oedema with right ventricular overload. Severe aortic and mitral regurgitation, severe biventricular impairment and pulmonary hypertension were confirmed on transthoracic and transoesophageal echocardiography. An urgent transfemoral valve-in-valve transcatheter valve implantation (TAVI) was performed within the aortic valve homograft with full resolution of aortic regurgitation. Three months later, a semielective trans-apical valve-in-valve procedure was performed in the mitral position, under cardiopulmonary bypass, with full resolution of mitral regurgitation. His exercise tolerance increased from 5 yards to half a mile. This case report summarises a staged double valve-in-valve procedure in a patient who had three previous sternotomies and who had severe heart failure due to failing aortic and mitral bioprostheses. We report two different delivery approaches, using two different transcatheter devices, and describe valve-in-valve techniques, including cardiopulmonary bypass, in the catheter laboratory. PMID:25053698

  8. Impact of Pulmonary Hypertension on Outcomes Following Aortic Valve Replacement for Aortic Valve Stenosis

    PubMed Central

    Melby, Spencer J.; Moon, Marc R.; Lindman, Brian R.; Bailey, Marci S.; Hill, Laureen L.; Damiano, Ralph J.

    2011-01-01

    Objective The presence of pulmonary hypertension (PH) historically has been considered a significant risk factor affecting early and late outcomes following valve replacement. Given the number of recent advances in the management of PH following cardiac surgery a better understanding of the impact of PH on outcomes may assist in the clinical management of these patients. The purpose of this study was to determine if pulmonary hypertension remains a risk factor in the modern era for adverse outcomes following aortic valve replacement (AVR) for aortic valve stenosis. Methods From January 1996 to June 2009, 1,080 patients underwent AVR for primary aortic valve stenosis, of which 574 (53%) had normal systolic pulmonary artery pressures (sPAP) and 506 (47%) had PH. PH was defined as mild (sPAP 35-44 mmHg), moderate (45-59mmHg), or severe (≥ 60mmHg). In the group of patients with PH, 204 had postoperative echocardiograms. Results Operative mortality was significantly higher in patients with PH (47/506, 9% versus 31/574, 5%; p=0.02). The incidence of postoperative stroke was similar (p=0.14), but patients with PH had an increased median hospital LOS (8 versus 7 days, p=0.001) and an increased incidence of prolonged ventilation (26% versus 17%, p<0.001). Preoperative PH was an independent risk factor for decreased long term survival (RR 1.7, p=0.02). Those with persistent PH postoperatively had decreased survival. Five-year survival (Kaplan-Meier) was 78 ± 6% with normal sPAP and 77 ± 7% with mild PH postoperatively, compared to 64 ± 8% with moderate PH and 45 ± 12% with severe PH (p<0.001). Conclusion In patients undergoing AVR, preoperative PH increased operative mortality and decreased long-term survival. Patients with persistent moderate or severe PH after AVR had decreased long-term survival. These data suggest that PH had a significant impact on outcomes in patients undergoing AVR and should be considered in preoperative risk assessment. PMID:21596173

  9. Analysis of Oxidative Stress Enzymes and Structural and Functional Proteins on Human Aortic Tissue from Different Aortopathies

    PubMed Central

    Soto, María Elena; Soria-Castro, Elizabeth; Guarner Lans, Verónica; Muruato Ontiveros, Eleazar; Iván Hernández Mejía, Benjamín; Jorge Martínez Hernandez, Humberto; Barragán García, Rodolfo; Herrera, Valentín; Pérez-Torres, Israel

    2014-01-01

    The role of oxidative stress in different aortopathies is evaluated. Thirty-two tissue samples from 18 men and 14 women were divided into: 4 control (C) subjects, 11 patients with systemic arterial hypertension (SAH), 4 with variants of Marfan's syndrome (MV), 9 with Marfan's syndrome (M), 2 with Turner's syndrome, and 2 with Takayasu's arteritis (TA). Aorta fragments were homogenized. Lipoperoxidation (LPO), copper-zinc and manganese superoxide dismutase (Mn and Cu-Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), endothelial nitric oxide synthase (eNOS), nitrates and nitrites (NO3−/NO2−), and type IV collagen, and laminin were evaluated. There was an increase in Mn- and Cu-Zn-SOD activity in SAH, MV, M, and Turner's syndrome. There was also an increase in CAT activity in M and Turner' syndrome. GPx and GST activity decreased and LPO increased in all groups. eNOS was decreased in SAH, MV, and M and NO3−/NO2− were increased in SAH and TA. Type IV collagen was decreased in Turner's syndrome and TA. Laminin γ-1 was decreased in MV and increased in M. In conclusion, similarities and differences in oxidative stress in the different aortopathies studied including pathologies with aneurysms were found with alterations in SOD, CAT, GPx, GST, and eNOS activity that modify subendothelial basement membrane proteins. PMID:25101153

  10. Analysis of oxidative stress enzymes and structural and functional proteins on human aortic tissue from different aortopathies.

    PubMed

    Soto, María Elena; Soria-Castro, Elizabeth; Lans, Verónica Guarner; Ontiveros, Eleazar Muruato; Mejía, Benjamín Iván Hernández; Hernandez, Humberto Jorge Martínez; García, Rodolfo Barragán; Herrera, Valentín; Pérez-Torres, Israel

    2014-01-01

    The role of oxidative stress in different aortopathies is evaluated. Thirty-two tissue samples from 18 men and 14 women were divided into: 4 control (C) subjects, 11 patients with systemic arterial hypertension (SAH), 4 with variants of Marfan's syndrome (MV), 9 with Marfan's syndrome (M), 2 with Turner's syndrome, and 2 with Takayasu's arteritis (TA). Aorta fragments were homogenized. Lipoperoxidation (LPO), copper-zinc and manganese superoxide dismutase (Mn and Cu-Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), endothelial nitric oxide synthase (eNOS), nitrates and nitrites (NO3(-)/NO2(-)), and type IV collagen, and laminin were evaluated. There was an increase in Mn- and Cu-Zn-SOD activity in SAH, MV, M, and Turner's syndrome. There was also an increase in CAT activity in M and Turner' syndrome. GPx and GST activity decreased and LPO increased in all groups. eNOS was decreased in SAH, MV, and M and NO3 (-)/NO2 (-) were increased in SAH and TA. Type IV collagen was decreased in Turner's syndrome and TA. Laminin γ-1 was decreased in MV and increased in M. In conclusion, similarities and differences in oxidative stress in the different aortopathies studied including pathologies with aneurysms were found with alterations in SOD, CAT, GPx, GST, and eNOS activity that modify subendothelial basement membrane proteins. PMID:25101153

  11. Paraoxonase-1 overexpression prevents experimental abdominal aortic aneurysm progression.

    PubMed

    Burillo, Elena; Tarin, Carlos; Torres-Fonseca, Monica-Maria; Fernandez-García, Carlos-Ernesto; Martinez-Pinna, Roxana; Martinez-Lopez, Diego; Llamas-Granda, Patricia; Camafeita, Emilio; Lopez, Juan Antonio; Vega de Ceniga, Melina; Aviram, Michael; Egido, Jesus; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

    2016-06-01

    Abdominal aortic aneurysm (AAA) is a permanent dilation of the aorta due to excessive proteolytic, oxidative and inflammatory injury of the aortic wall. We aimed to identify novel mediators involved in AAA pathophysiology, which could lead to novel therapeutic approaches. For that purpose, plasma from four AAA patients and four controls were analysed by a label-free proteomic approach. Among identified proteins, paraoxonase-1 (PON1) was decreased in plasma of AAA patients compared with controls, which was further validated in a bigger cohort of samples by ELISA. The phenylesterase enzymatic activity of PON1 was also decreased in serum of AAA patients compared with controls. To address the potential role of PON1 as a mediator of AAA, experimental AAA was induced by aortic elastase perfusion in wild-type (WT) mice and human transgenic PON1 (HuTgPON1) mice. Similar to humans, PON1 activity was also decreased in serum of elastase-induced AAA mice compared with healthy mice. Interestingly, overexpression of PON1 was accompanied by smaller aortic dilation and higher elastin and vascular smooth muscle cell (VSMC) content in the AAA of HuTgPON1 compared with WT mice. Moreover, HuTgPON1 mice display decreased oxidative stress and apoptosis, as well as macrophage infiltration and monocyte chemoattractant protein-1 (MCP1) expression, in elastase-induced AAA. In conclusion, decreased circulating PON1 activity is associated with human and experimental AAA. PON1 overexpression in mice protects against AAA progression by reducing oxidative stress, apoptosis and inflammation, suggesting that strategies aimed at increasing PON1 activity could prevent AAA. PMID:26993251

  12. Evidence of deregulated cholesterol efflux in abdominal aortic aneurysm.

    PubMed

    Mourmoura, Evanthia; Vasilaki, Anna; Giannoukas, Athanasios; Michalodimitrakis, Emmanouel; Pavlidis, Pavlos; Tsezou, Aspasia

    2016-03-01

    Previous studies indicated that lipids may be associated with abdominal aortic aneurysm (AAA); however the molecular mechanism involved is unclear. Our study aimed to investigate the expression pattern of cholesterol efflux related proteins in AAA. Liver X receptors (LXRα and LXRβ), ATP-binding-cassette transporter A1 (ABCA1), Apolipoprotein AI (ApoAI), smooth muscle α-actin (α-SM) and vimentin expression levels were evaluated in human AAA, atherosclerotic (ATH) and normal abdominal aortic tissues. We found significant differences in LXRα, LXRβ and ABCA1 mRNA expression levels between AAA, ATH and normal whole aortic tissues and also within the AAA, ATH and normal "intima-media" layers. Specifically, LXRα, LXRβ and ABCA1 mRNA levels were decreased in AAA compared to ATH-whole tissues, as well as in AAA "intima-media" compared to ATH and normal "intima-media" layers. Moreover, immunohistochemical evaluation revealed that LXRα and ABCA1 immunoreactivities (IR) were reduced in the AAA media compared to the normal and ATH media layers and that they were also reduced in the intima layer of AAA and ATH tissues, whereas ApoAI-IR was increased in the AAA and ATH aortic walls compared to normal pointing to possible deregulation of the cholesterol efflux mechanism in AAA. Furthermore, double staining for vimentin and α-SM showed vimentin expression in the intima and inner media layer of AAA with sparse vimentin positive SMCs designating possible SMCs phenotype switch from contractile to synthetic form. In addition, histochemical analysis showed excessive lipid accumulation in the AAA wall, while co-staining using Oil Red O with α-SM or CD68 revealed lipid accumulation in SMCs and macrophages, respectively. Our study provides novel evidence for impaired cholesterol efflux in AAA associated with lipid accumulation in SMCs and macrophages, as well as switch of SMCs phenotype from contractile to synthetic form. PMID:26725543

  13. Feature identification for image-guided transcatheter aortic valve implantation

    NASA Astrophysics Data System (ADS)

    Lang, Pencilla; Rajchl, Martin; McLeod, A. Jonathan; Chu, Michael W.; Peters, Terry M.

    2012-02-01

    Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to open-heart surgery, and is critically dependent on imaging for accurate placement of the new valve. Augmented image-guidance for TAVI can be provided by registering together intra-operative transesophageal echo (TEE) ultrasound and a model derived from pre-operative CT. Automatic contour delineation on TEE images of the aortic root is required for real-time registration. This study develops an algorithm to automatically extract contours on simultaneous cross-plane short-axis and long-axis (XPlane) TEE views, and register these features to a 3D pre-operative model. A continuous max-flow approach is used to segment the aortic root, followed by analysis of curvature to select appropriate contours for use in registration. Results demonstrate a mean contour boundary distance error of 1.3 and 2.8mm for the short and long-axis views respectively, and a mean target registration error of 5.9mm. Real-time image guidance has the potential to increase accuracy and reduce complications in TAVI.

  14. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    MedlinePlus Videos and Cool Tools

    Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2016 BroadcastMed, Inc. All rights reserved.

  15. A rare cause of recurrent aortic dissection.

    PubMed

    Agrawal, Yashwant; Gupta, Vishal

    2016-07-01

    We report the case of a 19-year-old man with a history of Loeys-Dietz syndrome (LDS), which was diagnosed when he had a Stanford type A aortic dissection. He also had multiple aneurysms including ones in the innominate, right common carotid, and right internal mammary arteries. He had had multiple procedures including Bentall's procedure, repeat sternotomy with complete arch and valve replacement, and coil embolization of internal mammary artery aneurysm in the past. His LDS was characterized by gene mutation for transforming growth factor-β receptor 1. He presented to our facility with sudden onset of back pain, radiating to the right shoulder and chest. He was diagnosed with Stanford type B aortic dissection and underwent thoracic aorta endovascular repair for his aortic dissection. This case represents the broad spectrum of pathology associated with LDS where even with regular surveillance and aggressive medical management the patient developed Stanford B aortic dissection. PMID:27358537

  16. Endovascular repair of thoracic aortic aneurysms.

    PubMed

    Cartes-Zumelzu, F; Lammer, J; Kretschmer, G; Hoelzenbein, T; Grabenwöger, M; Thurnher, S

    2000-03-01

    The standard technique for the treatment of descending thoracic aortic aneurysms is elective open surgical repair with graft interposition. This standard approach, although steadily improving, is associated with high morbidity and substantial mortality rates and implies a major surgical procedure with lateral thoracotomy, use of cardiopulmonary bypass, long operation times and a variety of peri- and postoperative complications. This and the success of the first endoluminal treatment of abdominal aortic aneurysms by Parodi et al. prompted the attention to be thrown on the treatment of descending thoracic aortic aneurysms with endoluminal stent-grafts in many large centres. The aim of this new minimally invasive technique is to exclude the aneurysm from blood flow and in consequence to avoid pressure stress on the aneurysmatic aortic wall, by avoiding a large open operation with significant perioperative morbidity. The potentially beneficial effect of this new treatment approach was evaluated in the course of this study. PMID:10875224

  17. Anaesthetic management of aortic coarctation in pregnancy.

    PubMed

    Walker, E; Malins, A F

    2004-10-01

    We report two cases of aortic coarctation in pregnancy. The first was a 20-year-old nulliparous woman who underwent an aortic coarctation repair when she was 23 weeks old and subsequently developed an aneurysm at the site of initial repair. The second was a 20-year-old nulliparous woman with a severe uncorrected congenital aortic coarctation and upper body hypertension, who became pregnant whilst awaiting transcatheter dilatation of the coarctation. Antenatal care involved a multidisciplinary approach with obstetric, anaesthetic and cardiology input. Both parturients were delivered by elective caesarean section. A cautious, incremental regional anaesthetic technique was used, with no associated maternal or neonatal morbidity. Perioperative management focused on minimising haemodynamic disturbances. The management is discussed, together with the potential maternal and fetal complications of aortic coarctation in pregnancy. PMID:15477059

  18. Understanding the pathogenesis of abdominal aortic aneurysms

    PubMed Central

    Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Tromp, Gerard

    2016-01-01

    Summary An aortic aneurysm is a dilatation in which the aortic diameter is ≥ 3.0 cm. If left untreated, the aortic wall continues to weaken and becomes unable to withstand the forces of the luminal blood pressure resulting in progressive dilatation and rupture, a catastrophic event associated with a mortality of 50 – 80%. Smoking and positive family history are important risk factors for the development of abdominal aortic aneurysms (AAA). Several genetic risk factors have also been identified. On the histological level, visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. We expect that large genetic, genomic, epigenetic, proteomic and metabolomic studies will be undertaken by international consortia to identify additional risk factors and biomarkers, and to enhance our understanding of the pathobiology of AAA. Collaboration between different research groups will be important in overcoming the challenges to develop pharmacological treatments for AAA. PMID:26308600

  19. Approach to the patient with bicuspid aortic valve and ascending aorta aneurysm.

    PubMed

    Ortiz, José T; Shin, David D; Rajamannan, Nalini M

    2006-12-01

    Bicuspid aortic valve (BAV) disease is a common congenital heart valve abnormality accounting for a large number of valve replacements in the United States. Although still incompletely understood, the natural history of BAV disease is severe aortic stenosis and associated ascending aortic dilatation. In addition to the increased risk of endocarditis, aortic dissection and severe aortic valve dysfunction are responsible for most fatal complications. Thus, early and precise recognition of this condition is mandatory. The new American College of Cardiology/American Heart Association recommendations highlight the role of MRI and CT as complimentary tools to echocardiography for the diagnosis and surveillance of the morphology of the aortic valve and ascending aorta. Moreover, better understanding of the cellular mechanisms, including inflammation, bone formation, atherosclerotic-like processes, and aortic wall abnormalities, as well as the heritability and genetic predisposition for the disease, will define the potential for targeted medical therapies in the future. Currently, the treatment of this condition is primarily surgical. Although combined valve and ascending aorta replacement has been the most common surgical approach in the past, the increased cumulative risk of thrombotic and embolic events among these young patients has led to more conservative approaches. Several valve-sparing approaches with comparable mid-term results compared with the classic procedures have recently been reported. However, longer follow-up studies will be helpful to better define the advantages of these new surgical options. After a quick overview of the natural history of the BAV, this article provides an updated approximation of the current knowledge of the pathophysiology as well as the recommendations for the management and treatment of this disease. PMID:17078910

  20. Laparoscopic extraperitoneal para-aortic lymphadenectomy

    PubMed Central

    Iserte, Pablo Padilla; Minig, Lucas; Zorrero, Cristina

    2015-01-01

    Lymph nodes are the main pathway in the spread of gynaecological malignancies, being a well-known prognostic factor. Lymph node dissection is a complex surgical procedure and requires surgical expertise to perform the procedure, thereby minimising complications. In addition, lymphadenectomy has value in the diagnosis, prognosis, and treatment of patients with gynaecologic cancer. Therefore, a video focused on the para-aortic retroperitoneal anatomy and the surgical technique of the extraperitoneal para-aortic lymphadenectomy is presented. PMID:26435746

  1. Peripartum presentation of an acute aortic dissection.

    PubMed

    Lewis, S; Ryder, I; Lovell, A T

    2005-04-01

    We report the case of an acute type A aortic dissection occurring in a 35-year-old parturient. The initial diagnosis was missed; a subsequent emergency Caesarean section 3 weeks after presentation was followed by the development of left ventricular failure and pulmonary oedema in the early postoperative period. Echocardiography confirmed the diagnosis of aortic dissection and the patient underwent a successful surgical repair. PMID:15640303

  2. Aortic Dissection Type A in Alpine Skiers

    PubMed Central

    Schachner, Thomas; Fischler, Nikolaus; Dumfarth, Julia; Bonaros, Nikolaos; Krapf, Christoph; Schobersberger, Wolfgang; Grimm, Michael

    2013-01-01

    Patients and Methods. 140 patients with aortic dissection type A were admitted for cardiac surgery. Seventy-seven patients experienced their dissection in the winter season (from November to April). We analyzed cases of ascending aortic dissection associated with alpine skiing. Results. In 17 patients we found skiing-related aortic dissections. Skiers were taller (180 (172–200) cm versus 175 (157–191) cm, P = 0.008) and heavier (90 (68–125) kg versus 80 (45–110) kg, P = 0.002) than nonskiers. An extension of aortic dissection into the aortic arch, the descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and 69%, respectively, with no significant difference between skiers and nonskiers. Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was true for 5% of nonskiers (P = 0.086). Hospital mortality of skiers was 6% versus 13% in nonskiers (P = 0.399). The skiers live at an altitude of 170 (0–853) m.a.s.l. and experience their dissection at 1602 (1185–3105; P < 0.001) m.a.s.l. In 82% symptom start was during recreational skiing without any trauma. Conclusion. Skiing associated aortic dissection type A is usually nontraumatic. The persons affected live at low altitudes and practice an outdoor sport at unusual high altitude at cold temperatures. Postoperative outcome is good. PMID:23971024

  3. Abnormalities in aortic properties: a potential link between left ventricular diastolic function and ventricular-aortic coupling in sickle cell disease.

    PubMed

    Bollache, Emilie; Kachenoura, Nadjia; Lang, Roberto M; Desai, Ankit A; Mor-Avi, Victor; Patel, Amit R

    2016-06-01

    Left ventricular (LV) diastolic dysfunction in patients with sickle cell disease (SCD) is associated with increased mortality. However, its mechanisms are not well known, preventing the development of effective therapies. We hypothesized that patients with SCD have altered aortic properties despite normal blood pressure, which may contribute towards the development of diastolic dysfunction. We studied 31 stable adult patients with SCD (32 ± 7 years) and 12 healthy controls of similar age (29 ± 10 years) who underwent echocardiography and cardiovascular magnetic resonance (CMR) imaging on the same day. Echocardiographic measurements of mitral inflow and mitral annulus velocities were used to evaluate LV diastolic function. CMR imaging included standard LV function evaluation and myocardial tissue characterization as well as velocity-encoded images of the ascending aorta to measure aortic diastolic cross-sectional area, distensibility, as well as peaks and volumes of the global, forward and backward blood flow rate. Compared to controls, SCD patients had increased aortic diastolic area, global stroke volume, and both forward and backward flow, while aortic distensibility and peripheral blood pressure were similar. Furthermore, peak backward flow rate and volume were able to discriminate between patients with and without diastolic dysfunction. Our findings show that some aortic properties are altered in SCD patients and may be associated with diastolic dysfunction despite normal systolic blood pressure. If confirmed in larger studies, these aortic changes could be a novel therapeutic target to prevent or delay the development of LV diastolic dysfunction in SCD and thus potentially improve outcomes in these patients. PMID:26907920

  4. [Total aortic arch replacement in Stanford type A aortic dissection using a new method of implanting the stented graft].

    PubMed

    Kiyama, Hiroshi; Kaki, Nobuaki; Shiomi, Daisuke; Shimada, Naohiro

    2012-07-01

    In surgery for Stanford type A aortic dissection (SAAD) with intimal tear in the arch or proximal descending aorta, we performed total arch replacement with frozen elephant trunk technique for the purpose of achieving complete exclusion of the entry. To reduce the circulatory arrest time, we developed a quick stent graft placement method in the proximal descending aorta. We reported the early results and assessed the efficacy of our new method. Between March 2006 and February 2010, 52 consecutive patients with SAAD were divided into 2 groups:group A consisted of 17 patients who received total arch replacement with our new method;group B consisted of 35 patients who received ascending aorta or partial arch replacement. The duration of operation and cardiopulmonary bypass were significantly longer in group A. However, the duration of circulatory arrest time and postoperative factors including hospital mortality did not differ in both groups. In group A, thrombus obliteration of the residual false lumen in the descending aorta was observed in 75% at 19.2±13.1 months postoperatively. Shrinkage of false lumen in the aortic arch occurred in 15 patients( 93.8%). There was no reoperation for the residual false lumen and late death. Total aortic arch replacement with our new method for SAAD is technically feasible without increasing the operative risk and might reduce the necessity for further operations. PMID:22750824

  5. Aortic valve surgery: what is the future?

    PubMed

    Hudorović, Narcis

    2008-04-01

    Modern surgical treatment for aortic valve disease has undergone significant improvements in all areas of this procedure. Successful treatment strategies for cardiovascular diseases have often been initiated and driven by surgeons. Radical excision of diseased tissue, repair and replacement strategies lead to long-term successful treatment of the underlying diseases and clearly improved patient outcome. In highly developed nations, valve surgery will be increasing applied in older people, with more co-morbidities and a higher incidence of concomitant coronary artery disease. Cardiovascular surgeons will be facing increased competition from the catheter-based procedures; these are already applied clinically, and their numbers will rise in near future. Right now interventional cardiologists supported by some cardiac surgeons are on their way to transform some conventional open surgical procedures into catheter-based less invasive interventions, such as valve repair and replacement. Cardiovascular surgery is undergoing a rapid transformation; socio-economic factors and recent advances in medical technology contribute to these changes. Further developments will come, and surgeons with all their expertise in the treatment of valvular heart disease need to be part of it. Cardiovascular surgeons have to adapt the exciting new approaches of transapical and transfemoral transcatheter valve implantation techniques. PMID:17573248

  6. Endovascular treatment of abdominal aortic aneurysms.

    PubMed

    Buck, Dominique B; van Herwaarden, Joost A; Schermerhorn, Marc L; Moll, Frans L

    2014-02-01

    Patients with abdominal aortic aneurysms (AAAs) are usually treated with endovascular aneurysm repair (EVAR), which has become the standard of care in many hospitals for patients with suitable anatomy. Clinical evidence indicates that EVAR is associated with superior perioperative outcomes and similar long-term survival compared with open repair. Since the randomized, controlled trials that provided this evidence were conducted, however, the stent graft technology for infrarenal AAA has been further developed. Improvements include profile downsizing, optimization of sealing and fixation, and the use of low porosity fabrics. In addition, imaging techniques have improved, enabling better preoperative planning, stent graft placement, and postoperative surveillance. Also in the past few years, fenestrated and branched stent grafts have increasingly been used to manage anatomically challenging aneurysms, and experiments with off-label use of stent grafts have been performed to treat patients deemed unfit or unsuitable for other treatment strategies. Overall, the indications for endovascular management of AAA are expanding to include increasingly complex and anatomically challenging aneurysms. Ongoing studies and optimization of imaging, in addition to technological refinement of stent grafts, will hopefully continue to broaden the utilization of EVAR. PMID:24343568

  7. General Considerations of Ruptured Abdominal Aortic Aneurysm: Ruptured Abdominal Aortic Aneurysm

    PubMed Central

    Lee, Chung Won; Bae, Miju; Chung, Sung Woon

    2015-01-01

    Although development of surgical technique and critical care, ruptured abdominal aortic aneurysm still carries a high mortality. In order to obtain good results, various efforts have been attempted. This paper reviews initial management of ruptured abdominal aortic aneurysm and discuss the key point open surgical repair and endovascular aneurysm repair. PMID:25705591

  8. eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease

    PubMed Central

    İlhan, Nevin; Ateş, Kadir; İlhan, Necip; Kaman, Dilara; Çeliker, Hüseyin

    2016-01-01

    Background: Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. Aims: The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. Study Design: Case-control study. Methods: In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. Conclusion: Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients. PMID:27403380

  9. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells.

    PubMed

    Fleming, Ingrid; Fisslthaler, Beate; Dixit, Madhulika; Busse, Rudi

    2005-09-15

    The application of fluid shear stress to endothelial cells elicits the formation of nitric oxide (NO) and phosphorylation of the endothelial NO synthase (eNOS). Shear stress also elicits the enhanced tyrosine phosphorylation of endothelial proteins, especially of those situated in the vicinity of cell-cell contacts. Since a major constituent of these endothelial cell-cell contacts is the platelet endothelial cell adhesion molecule-1 (PECAM-1) we assessed the role of PECAM-1 in the activation of eNOS. In human endothelial cells, shear stress induced the tyrosine phosphorylation of PECAM-1 and enhanced the association of PECAM-1 with eNOS. Endothelial cell stimulation with shear stress elicited the phosphorylation of Akt and eNOS as well as of the AMP-activated protein kinase (AMPK). While the shear-stress-induced tyrosine phosphorylation of PECAM-1 as well as the serine phosphorylation of Akt and eNOS were abolished by the pre-treatment of cells with the tyrosine kinase inhibitor PP1 the ph