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Sample records for aortic enos expression

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

    PubMed

    Mueller, Konrad E; Wolf, Katerina

    2015-01-01

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

  2. 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

  3. 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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

  8. 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

  9. Molecular beacons can assess changes in expression and 3'-polyadenylation of human eNOS mRNA.

    PubMed

    Jones, Rachel; Baker, Meredith B; Weber, Martina; Harrison, David G; Bao, Gang; Searles, Charles D

    2009-03-01

    The endothelium plays an essential role in maintaining vascular homeostasis, and it fulfills this role by modulating intracellular signaling and gene expression in response to chemical and mechanical stimuli. Assessing changes in endothelial gene expression is essential to understanding how physiological and pathophysiological processes modulate vascular homeostasis. Here we describe the use of molecular beacons to rapidly and quantitatively assess expression and 3'-polyadenylation of a gene that is important for vascular homeostasis, endothelial nitric oxide synthase (eNOS). Single- and dual-fluorescence resonance energy transfer (FRET) molecular beacon hybridization assays were developed to measure changes in mRNA levels and 3'-polyadenylation, respectively, in primary human endothelial cell cultures subjected to laminar shear stress or statin treatment. Optimized beacon hybridization assays took approximately 15 min to perform, and eNOS mRNA levels were validated by quantitative real-time RT-PCR. Competitive inhibition assays and posttranscriptional silencing of eNOS expression were used to verify the specificity of molecular beacon fluorescence. Finally, the dual-FRET method was used to assess eNOS polyadenylation in tissues isolated from mice subjected to exercise training. These data demonstrate that molecular beacons can be used to rapidly and efficiently measure endothelial gene expression and 3'-polyadenylation. This approach could easily be adapted for studies of other endothelial genes and has promise for applications in live endothelial cells.

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

    PubMed Central

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

    2016-01-01

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

  11. Comparison of gene expression profiles in aortic dissection and normal human aortic tissues

    PubMed Central

    Zhang, Liang; Yu, Cuntao; Chang, Qian; Luo, Xinjin; Qiu, Juntao; Liu, Shen

    2016-01-01

    The aim of the present study was to compare the gene expression profiles in aortic dissection (AD) and healthy human aortic tissue samples by DNA microarray analysis in order to screen the differential genes. In total, five AD and four healthy aortic specimens were selected; the total RNA was extracted and reverse transcribed into cDNA and in vitro transcribed into aRNA, followed by microarray hybridization for analysis. Thereafter, the transcription levels of six differential genes, myosin light chain kinase (MYLK), polycystin 1, transient receptor potential channel interacting (PKD-1), myosin heavy chain 11 (MYH11), superoxide dismutase 3, extracellular (SOD3), filamin A (FLNA), and transgelin (TAGLN), screened from the expression profiles were quantitatively verified. Compared with the healthy aortic specimens, a total of 1,661 genes in the AD group demonstrated more than 2-fold differential expression, of which 997 genes were upregulated and 664 genes were downregulated. Thereafter, six AD-associated genes that showed downregulation in the microarray assay were selected for quantitatively verifying the gene transcription level using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which confirmed their downregulation compared with the healthy aortic tissue genes; of the six genes, the expression levels of MYLK, PKD-1, MYH11, SOD3 and TAGLN were significantly downregulated (P<0.05), while the expression of FLNA was not significantly downregulated (P>0.05). Thus, whole genome microarray may be used to screen differentially expressed genes between AD and healthy aortic tissues. When used in combination with RT-qPCR validation, this method may provide novel strategies for investigating AD. PMID:27699008

  12. Comparison of gene expression profiles in aortic dissection and normal human aortic tissues

    PubMed Central

    Zhang, Liang; Yu, Cuntao; Chang, Qian; Luo, Xinjin; Qiu, Juntao; Liu, Shen

    2016-01-01

    The aim of the present study was to compare the gene expression profiles in aortic dissection (AD) and healthy human aortic tissue samples by DNA microarray analysis in order to screen the differential genes. In total, five AD and four healthy aortic specimens were selected; the total RNA was extracted and reverse transcribed into cDNA and in vitro transcribed into aRNA, followed by microarray hybridization for analysis. Thereafter, the transcription levels of six differential genes, myosin light chain kinase (MYLK), polycystin 1, transient receptor potential channel interacting (PKD-1), myosin heavy chain 11 (MYH11), superoxide dismutase 3, extracellular (SOD3), filamin A (FLNA), and transgelin (TAGLN), screened from the expression profiles were quantitatively verified. Compared with the healthy aortic specimens, a total of 1,661 genes in the AD group demonstrated more than 2-fold differential expression, of which 997 genes were upregulated and 664 genes were downregulated. Thereafter, six AD-associated genes that showed downregulation in the microarray assay were selected for quantitatively verifying the gene transcription level using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which confirmed their downregulation compared with the healthy aortic tissue genes; of the six genes, the expression levels of MYLK, PKD-1, MYH11, SOD3 and TAGLN were significantly downregulated (P<0.05), while the expression of FLNA was not significantly downregulated (P>0.05). Thus, whole genome microarray may be used to screen differentially expressed genes between AD and healthy aortic tissues. When used in combination with RT-qPCR validation, this method may provide novel strategies for investigating AD.

  13. Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease

    PubMed Central

    Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan

    2015-01-01

    Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms. PMID:25944698

  14. 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

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

    PubMed

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

    2015-03-13

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

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

    PubMed

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

    2015-06-01

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

  18. Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

    PubMed

    Azuma, Junya; Wong, Ronald J; Morisawa, Takeshi; Hsu, Mark; Maegdefessel, Lars; Zhao, Hui; Kalish, Flora; Kayama, Yosuke; Wallenstein, Matthew B; Deng, Alicia C; Spin, Joshua M; Stevenson, David K; Dalman, Ronald L; Tsao, Philip S

    2016-01-01

    Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease.

  19. Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

    PubMed

    Azuma, Junya; Wong, Ronald J; Morisawa, Takeshi; Hsu, Mark; Maegdefessel, Lars; Zhao, Hui; Kalish, Flora; Kayama, Yosuke; Wallenstein, Matthew B; Deng, Alicia C; Spin, Joshua M; Stevenson, David K; Dalman, Ronald L; Tsao, Philip S

    2016-01-01

    Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease. PMID:26894432

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

    PubMed

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

    2005-10-01

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

  1. Endogenous Reference Genes for Gene Expression Studies on Bicuspid Aortic Valve Associated Aortopathy in Humans

    PubMed Central

    Harrison, Oliver J.; Moorjani, Narain; Torrens, Christopher; Ohri, Sunil K.; Cagampang, Felino R.

    2016-01-01

    Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality and predisposes patients to life-threatening aortic complications including aortic aneurysm. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most commonly used methods to investigate underlying molecular mechanisms involved in aortopathy. The accuracy of the gene expression data is dependent on normalization by appropriate housekeeping (HK) genes, whose expression should remain constant regardless of aortic valve morphology, aortic diameter and other factors associated with aortopathy. Here, we identified an appropriate set of HK genes to be used as endogenous reference for quantifying gene expression in ascending aortic tissue using a spin column-based RNA extraction method. Ascending aortic biopsies were collected intra-operatively from patients undergoing aortic valve and/or ascending aortic surgery. These patients had BAV or tricuspid aortic valve (TAV), and the aortas were either dilated (≥4.5cm) or undilated. The cohort had an even distribution of gender, valve disease and hypertension. The expression stability of 12 reference genes were investigated (ATP5B, ACTB, B2M, CYC1, EIF4A2, GAPDH, SDHA, RPL13A, TOP1, UBC, YWHAZ, and 18S) using geNorm software. The most stable HK genes were found to be GAPDH, UBC and ACTB. Both GAPDH and UBC demonstrated relative stability regardless of valve morphology, aortic diameter, gender and age. The expression of B2M and SDHA were found to be the least stable HK genes. We propose the use of GAPDH, UBC and ACTB as reference genes for gene expression studies of BAV aortopathy using ascending aortic tissue. PMID:27727313

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

    PubMed Central

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

    1998-01-01

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

  3. Regulation of Thrombomodulin Expression and Release in Human Aortic Endothelial Cells by Cyclic Strain

    PubMed Central

    Davenport, Colin; Murphy, Ronan P.; Cummins, Philip M.

    2014-01-01

    Background and Objectives Thrombomodulin (TM), an integral membrane glycoprotein expressed on the lumenal surface of vascular endothelial cells, promotes anti-coagulant and anti-inflammatory properties. Release of functional TM from the endothelium surface into plasma has also been reported. Much is still unknown however about how endothelial TM is regulated by physiologic hemodynamic forces (and particularly cyclic strain) intrinsic to endothelial-mediated vascular homeostasis. Methods This study employed human aortic endothelial cells (HAECs) to investigate the effects of equibiaxial cyclic strain (7.5%, 60 cycles/min, 24 hrs), and to a lesser extent, laminar shear stress (10 dynes/cm2, 24 hrs), on TM expression and release. Time-, dose- and frequency-dependency studies were performed. Results Our initial studies demonstrated that cyclic strain strongly downregulated TM expression in a p38- and receptor tyrosine kinase-dependent manner. This was in contrast to the upregulatory effect of shear stress. Moreover, both forces significantly upregulated TM release over a 48 hr period. With continuing focus on the cyclic strain-induced TM release, we noted both dose (0–7.5%) and frequency (0.5–2.0 Hz) dependency, with no attenuation of strain-induced TM release observed following inhibition of MAP kinases (p38, ERK-1/2), receptor tyrosine kinase, or eNOS. The concerted impact of cyclic strain and inflammatory mediators on TM release from HAECs was also investigated. In this respect, both TNFα (100 ng/ml) and ox-LDL (10–50 µg/ml) appeared to potentiate strain-induced TM release. Finally, inhibition of neither MMPs (GM6001) nor rhomboids (3,4-dichloroisocoumarin) had any effect on strain-induced TM release. However, significantly elevated levels (2.1 fold) of TM were observed in isolated microparticle fractions following 7.5% strain for 24 hrs. Conclusions A preliminary in vitro investigation into the effects of cyclic strain on TM in HAECs is presented

  4. 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.

  5. Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia.

    PubMed

    Smith-Jackson, K; Hentschke, M R; Poli-de-Figueiredo, C E; Pinheiro da Costa, B E; Kurlak, L O; Broughton Pipkin, F; Czajka, A; Mistry, H D

    2015-05-01

    Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation. PMID:25707739

  6. MicroRNA Expression Signature in Degenerative Aortic Stenosis

    PubMed Central

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  7. MicroRNA Expression Signature in Degenerative Aortic Stenosis.

    PubMed

    Shi, Jing; Liu, Hui; Wang, Hui; Kong, Xiangqing

    2016-01-01

    Degenerative aortic stenosis, characterized by narrowing of the exit of the left ventricle of the heart, has become the most common valvular heart disease in the elderly. The aim of this study was to investigate the microRNA (miRNA) signature in degenerative AS. Through microarray analysis, we identified the miRNA expression signature in the tissue samples from healthy individuals (n = 4) and patients with degenerative AS (n = 4). Six miRNAs (hsa-miR-193a-3p, hsa-miR-29b-1-5p, hsa-miR-505-5p, hsa-miR-194-5p, hsa-miR-99b-3p, and hsa-miR-200b-3p) were overexpressed and 14 (hsa-miR-3663-3p, hsa-miR-513a-5p, hsa-miR-146b-5p, hsa-miR-1972, hsa-miR-718, hsa-miR-3138, hsa-miR-21-5p, hsa-miR-630, hsa-miR-575, hsa-miR-301a-3p, hsa-miR-636, hsa-miR-34a-3p, hsa-miR-21-3p, and hsa-miR-516a-5p) were downregulated in aortic tissue from AS patients. GeneSpring 13.1 was used to identify potential human miRNA target genes by comparing a 3-way comparison of predictions from TargetScan, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify potential pathways and functional annotations associated with AS. Twenty miRNAs were significantly differentially expressed between patients with AS samples and normal controls and identified potential miRNA targets and molecular pathways associated with this morbidity. This study describes the miRNA expression signature in degenerative AS and provides an improved understanding of the molecular pathobiology of this disease. PMID:27579316

  8. Bicuspid Aortic Cusp Fusion Morphology Alters Aortic 3D Outflow Patterns, Wall Shear Stress and Expression of Aortopathy

    PubMed Central

    Mahadevia, Riti; Barker, Alex J; Schnell, Susanne; Entezari, Pegah; Kansal, Preeti; Fedak, Paul W.M.; Malaisrie, S Chris; McCarthy, Patrick; Collins, Jeremy; Carr, James; Markl, Michael

    2014-01-01

    Background: Aortic 3D blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy. Methods and Results: 4D flow MRI measured in vivo 3D blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4mm; n=15 RN-BAV, 39.6±7.2mm); aorta size controls with tricuspid aortic valves (n=30, 41.1±4.4mm); healthy volunteers (n=15, 24.9±3.0mm). Aortopathy type (0-3), systolic flow angle, flow displacement, and regional wall shear stress (WSS) were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional WSS (p<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV compared to aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV were associated with altered flow displacement in the proximal and mid AAo for type 1 (42-81% decrease versus type 2) and distal AAo for type 3 (33-39% increase versus type 2). Conclusions: The presence and type of BAV fusion was associated with changes in regional WSS distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiologic mechanism by which valve morphology phenotype can influence phenotypes of BAV aortopathy. PMID:24345403

  9. 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.

  10. 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

  11. 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

  12. Androgen Receptor (AR) Promotes Abdominal Aortic Aneurysm (AAA) Development via Modulating Inflammatory IL1α and TGFβ1 Expression

    PubMed Central

    Huang, Chiung-Kuei; Luo, Jie; Lai, Kuo-Pao; Wang, Ronghao; Pang, Haiyan; Chang, Eugene; Yan, Chen; Sparks, Janet; Lee, Soo Ok; Cho, Joshua; Chang, Chawnshang

    2015-01-01

    Gender difference is a risk factor for abdominal aortic aneurism formation yet the reason for male predominance remains unclear. Androgen and the androgen receptor influence the male gender difference, indicating that androgen receptor signaling may affect abdominal aortic aneurism development. Using angiotensin II induced abdominal aortic aneurism in apolipoprotein E null mouse models (82.4% abdominal aortic aneurism incidence), we found that mice lacking androgen receptor failed to develop abdominal aortic aneurism and aorta had dramatically reduced macrophages infiltration and intact elastic fibers. These findings suggested that androgen receptor expression in endothelial cells, macrophages or smooth muscle cells might play a role in abdominal aortic aneurism development. Selective knockout of androgen receptor in each of these cell types further demonstrated that mice lacking androgen receptor in macrophages (20% abdominal aortic aneurism incidence) or smooth muscle cells (12.5% abdominal aortic aneurism incidence), but not in endothelial cells (71.4% abdominal aortic aneurism incidence) had suppressed abdominal aortic aneurism development. Mechanism dissection showed that androgen receptor functioned through modulation of interleukin 1α and transforming growth factor β1 signals and by targeting androgen receptor with androgen receptor degradation enhancer ASC-J9® led to significant suppression of abdominal aortic aneurism development. These results demonstrate the underlying mechanism by which androgen receptor influences abdominal aortic aneurism development through interleukin 1α and transforming growth factor β1, and provides a potential new therapy to suppress/prevent abdominal aortic aneurism by targeting androgen receptor with ASC-J9®. PMID:26324502

  13. 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

  14. 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

  15. Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

    PubMed Central

    Black, S M; Johengen, M J; Ma, Z D; Bristow, J; Soifer, S J

    1997-01-01

    At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O2 ventilation increased PBF and decreased PVR more than rhythmic distension (P < 0.05). Rhythmic distension increased eNOS mRNA expression; O2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression (P < 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O2 or to shear stress. 95% O2 increased eNOS mRNA and protein expression (P < 0.05). Shear stress increased eNOS mRNA and protein expression (P < 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth. PMID:9294110

  16. 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

  17. Identification of a novel flow-mediated gene expression signature in patients with bicuspid aortic valve.

    PubMed

    Maleki, Shohreh; Björck, Hanna M; Folkersen, Lasse; Nilsson, Roland; Renner, Johan; Caidahl, Kenneth; Franco-Cereceda, Anders; Länne, Toste; Eriksson, Per

    2013-01-01

    Individuals with bicuspid aortic valve (BAV) are at significantly higher risk of developing serious aortic complications than individuals with tricuspid aortic valves (TAV). Studies have indicated an altered aortic blood flow in patients with BAV; however, the extent to which altered flow influences the pathological state of BAV aorta is unclear. In the present study, we dissected flow-mediated aortic gene expression in patients undergoing elective open heart surgery. A large collection of public microarray data sets were firstly screened for consistent co-expression with five well-characterized flow-regulated genes (query genes). Genes with co-expression probability of >0.5 were selected and further analysed in expression profiles (127 arrays) from ascending aorta of BAV and TAV patients. Forty-four genes satisfied two filtering criteria: a significant correlation with one or more of the query genes (R > 0.40) and differential expression between patients with BAV and TAV. No gene fulfilled the criteria in mammary artery (88 arrays), an artery not in direct contact with the valve. Fifty-five percent of the genes significantly altered between BAV and TAV patients showed differential expression between two identified flow regions in the rat aorta. A large proportion of the identified genes were related to angiogenesis and/or wound healing, with pro-angiogenesis genes downregulated and inhibitory genes upregulated in patients with BAV. Moreover, differential expression of ZFP36, GRP116 and PKD2 was confirmed using immunohistochemistry. Implementing a new strategy, we have demonstrated an angiostatic gene expression signature in patients with BAV, indicating impaired wound healing in these patients, potentially involved in BAV-associated aortopathy. PMID:22903503

  18. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats.

    PubMed

    Berkban, Thewarid; Boonprom, Pattanapong; Bunbupha, Sarawoot; Welbat, Jariya Umka; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pakdeechote, Poungrat; Prachaney, Parichat

    2015-07-01

    The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks. L-NAME induced high systolic blood pressure (SBP) and increased heart rate (HR), hindlimb vascular resistance (HVR) and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg) prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability. PMID:26133972

  19. Kallistatin inhibits TGF-β-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression.

    PubMed

    Guo, Youming; Li, Pengfei; Bledsoe, Grant; Yang, Zhi-Rong; Chao, Lee; Chao, Julie

    2015-09-10

    Kallistatin, an endogenous protein, consists of two structural elements: active site and heparin-binding domain. Kallistatin exerts beneficial effects on fibrosis by suppressing transforming growth factor (TGF)-β synthesis in animal models. TGF-β is the most potent inducer of endothelial-mesenchymal transition (EndMT), which contributes to fibrosis and cancer. MicroRNA (miR)-21 is an important player in organ fibrosis and tumor invasion. Here we investigated the potential role of kallistatin in EndMT via modulation of miR-21 in endothelial cells. Human kallistatin treatment blocked TGF-β-induced EndMT, as evidenced by morphological changes as well as increased endothelial and reduced mesenchymal marker expression. Kallistatin also inhibited TGF-β-mediated reactive oxygen species (ROS) formation and NADPH oxidase expression and activity. Moreover, kallistatin antagonized TGF-β-induced miR-21 and Snail1 synthesis, Akt phosphorylation, NF-κB activation, and matrix metalloproteinase 2 (MMP2) synthesis and activation. Kallistatin via its heparin-binding site blocked TGF-β-induced miR-21, Snail1 expression, and ROS formation, as wild-type kallistatin, but not heparin-binding site mutant kallistatin, exerted the effect. Conversely, kallistatin through its active site stimulated the synthesis of endothelial nitric oxide synthase (eNOS), sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1); however, these effects were blocked by genistein, a tyrosine kinase inhibitor. This is the first study to demonstrate that kallistatin's heparin-binding site is crucial for preventing TGF-β-induced miR-21 and oxidative stress, while its active site is key for stimulating the expression of antioxidant genes via interaction with an endothelial surface tyrosine kinase. These findings reveal novel mechanisms of kallistatin in protection against fibrosis and cancer by suppressing EndMT.

  20. 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

  1. 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

  2. Elevated expression of runt-related transcription factors in human abdominal aortic aneurysm.

    PubMed

    Dubis, J; Litwin, M; Michalowska, D; Zuk, N; Szczepanska-Buda, A; Grendziak, R; Baczynska, D; Barc, P; Witkiewicz, W

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a multifactorial disease of unknown etiology. AAA is caused by segmental weakening of the aortic walls and progressive aortic dilation leading to the eventual rupture of the aorta, accompanied by intense inflammation. Additionally, studies have indicated a close relationship between the pathogenesis and progression of AAA and cellular immune responses in aneurysm wall tissue. The Runt-related genes (RUNX) encode multifunctional mediators of the of intracellular signal transduction pathways in vascular remodeling, endothelial function, immune response and inflammation. The aim of this study was to evaluate the expression level of RUNX regulatory genes in AAA tissues and to assess the correlations between them. The study was performed on AAA wall-tissue samples obtained from patients with AAA during open aneurysm repair and normal aortic tissues collected from healthy organ donors. There are no proven clinical management strategies or pharmaco-therapeutics to prevent AAA progression once an AAA has been detected. Moreover, so far no biomarkers have been established to indicate the disease status of AAA. Hence, understanding the pathogenesis of AAA has recently become an increasing priority in basic and translational vascular research. We identified significantly higher mRNA and protein level of all of three Runt-related genes in aneurysmal aorta compared to a normal aorta. Increased expression of RUNX2 was demonstrated for the first time in abdominal aortic aneurysm tissue. Additionally, relationships between the activity of RUNX genes in the pathological tissue were identified. The results of elevated expression of RUNX genes and their relationships in the AAA tissues suggest the involvement of conserved Runt-related genes in the pathophysiology of AAA development. PMID:27358138

  3. 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

  4. Female gender attenuates cytokine and chemokine expression and leukocyte recruitment in experimental rodent abdominal aortic aneurysms.

    PubMed

    Sinha, Indranil; Cho, Brenda S; Roelofs, Karen J; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    Female gender appears to be protective in the development of abdominal aortic aneurysms (AAAs). This study sought to identify gender differences in cytokine and chemokine expression in an experimental rodent AAA model. Male and female rodent aortas were perfused with either saline (control) or elastase to induce AAA formation. Aortic diameter was determined and aortic tissue was harvested on postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined using focused gene arrays. Immunohistochemistry was used to quantify aortic leukocyte infiltration. Data were analyzed by Student's t-tests and ANOVA. Elastase-perfused female rodents developed significantly smaller aneurysms compared to males by day 7 (93 +/- 10% vs. 201 +/- 25%, P = 0.003). Elastase-perfused female aortas exhibited a fivefold decrease in expression of the BMP family and ligands of the TNF superfamily compared to males. In addition, the expression of members of the TGF beta and VEGF families were three to fourfold lower in female elastase-perfused aortas compared to males. Multiple members of the interleukin, CC chemokine receptor, and CC ligand families were detectable in only the male elastase-perfused aortas. Female elastase-perfused aortas demonstrated a corollary twofold lower neutrophil count (females: 17.5 +/- 1.1 PMN/HPF; males: 41 +/- 5.2 neutrophils/HPF, P = 0.01) and a 1.5-fold lower macrophage count (females: 12 +/- 1.1 macrophages/HPF; males: 17.5 +/- 1.1 macrophages/HPF, P = 0.003) compared to male elastase-perfused aortas. This study documents decreased expression of multiple cytokines and chemokines and diminished leukocyte trafficking in female rat aortas compared to male aortas following elastase perfusion. These genes may contribute to the gender disparity seen in AAA formation. PMID:17182958

  5. Neuronatin: A New Inflammation Gene Expressed on the Aortic Endothelium of Diabetic Mice

    PubMed Central

    Mzhavia, Nino; Yu, Shuiqing; Ikeda, Shota; Chu, Tehua T.; Goldberg, Ira; Dansky, Hayes M.

    2008-01-01

    OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes. RESEARCH DESIGN AND METHODS—Aortic gene expression profiles of obese and diabetic db/db, high-fat diet–fed C57BL/6J, and control mice were obtained using mouse Affymetrix arrays. Neuronatin (Nnat) was selected for further analysis. To determine the function of Nnat, a recombinant adenovirus (Ad-Nnat) was used to overexpress the Nnat gene in primary endothelial cells and in the mouse aorta in vivo. RESULTS—Nnat, a gene of unknown vascular function, was upregulated in the aortas of db/db and high-fat diet–fed mice. Nnat gene expression was increased in db/db mouse aorta endothelial cells. Nnat protein was localized to aortic endothelium and was selectively increased in the endothelium of db/db mice. Infection of primary human aortic endothelial cells (HAECs) with Ad-Nnat increased expression of a panel of nuclear factor-κB (NF-κB)-regulated genes, including inflammatory cytokines, chemokines, and cell adhesion molecules. Infection of mouse carotid arteries in vivo with the Ad-Nnat increased expression of vascular cell adhesion molecule 1 protein. Nnat activation of NF-κB and inflammatory gene expression in HAECs was mediated through pathways distinct from tumor necrosis factor-α. Nnat expression stimulated p38, Jun NH2-terminal kinase, extracellular signal–related kinase, and AKT kinase phosphorylation. Phosphatidylinositol 3-kinase and p38 inhibitors prevented Nnat-mediated activation of NF-κB–induced gene expression. CONCLUSIONS—Nnat expression is increased in endothelial cells of obese and diabetic mouse blood vessels. The effects of Nnat on inflammatory pathways in vitro and in vivo suggest a pathophysiological role of this new gene in diabetic vascular diseases. PMID:18591389

  6. 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

  7. Silicic acid in drinking water prevents age-related alterations in the endothelium-dependent vascular relaxation modulating eNOS and AQP1 expression in experimental mice: an immunohistochemical study.

    PubMed

    Buffoli, Barbara; Foglio, Eleonora; Borsani, Elisa; Exley, Christopher; Rezzani, Rita; Rodella, Luigi Fabrizio

    2013-06-01

    The maintenance of endothelial integrity is of great importance in coping with age-related vascular alterations. Endothelium-derived nitric oxide is one of the various vasoactive substances able to regulate vascular tone and homeostasis, and whose decrease is known to be related with senescence in endothelial cells. There are reports on the efficacy of silicon, especially as silicic acid, in protecting vascular integrity during age-related vascular diseases. The aim of this study was to evaluate the ability of supplementation of silicic acid in drinking water in the maintenance of vascular health in a mouse model of early physiological aging. In particular, we evaluated the relationship between Si supplementation and endothelial nitric oxide synthase (eNOS) expression, taking into account also the aquaporin-1 (AQP-1) isoform that, as recently reported, seems to be involved in nitric oxide transport across cell membranes. Our results showed that silicic acid supplementation increased both eNOS and AQP-1 expression, suggesting that silicic acid modulation of endothelial nitric oxide synthase and aquaporin-1 could represent a potential strategy against age-related vascular senescence.

  8. Characterization of human aortic smooth muscle cells expressing HPV16 E6 and E7 open reading frames.

    PubMed Central

    Conroy, S. C.; Hart, C. E.; Perez-Reyes, N.; Giachelli, C. M.; Schwartz, S. M.; McDougall, J. K.

    1995-01-01

    A comparative study of human papillomavirus type 16 E6E7-transfected and normal human aortic smooth muscle cells by morphological, electron microscopic, immunofluorescent, and biochemical analyses demonstrated that the E6E7-expressing cells retained much of the phenotype of normal aortic smooth muscle cells, including expression of smooth muscle markers and appropriate growth responses to PDGF and heparin. These cells differed from normal vascular smooth muscle cells in that they had slightly altered morphology and a higher growth rate that was not due to an autocrine response to secreted PDGF, and they contained more polyribosomes than normal smooth muscle cells. Images Figure 2 Figure 4 Figure 5 PMID:7677186

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

    PubMed

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

    2013-08-01

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

  10. X-ray Structure of Engineered Human Aortic Preferentially Expressed Protein-1 (APEG-1)

    SciTech Connect

    Manjasetty,B.; Niesen, F.; Scheich, C.; Roske, Y.; Goetz, F.; Behlke, J.; Sievert, V.; Heinemann, U.; Buessow, K.

    2005-01-01

    Arterial smooth muscle cells (SMC) are essential for the formation and function of the cardiovascular system. Abnormalities in their growth can cause a wide range of human disorders such as atherosclerosis, the principal cause for heart failure, thus the leading cause for deaths in the western world. The molecular mechanisms that regulate SMC growth and differentiation are unclear partly due to the lack of specific markers and defined in vitro differentiation systems. The recently discovered Aortic Preferentially Expressed Protein-1 (APEG-1) may serve as a sensitive marker for vascular SMC differentiation. APEG-1 is expressed in differentiated vascular SMC in vivo and was found to be down-regulated rapidly in de-differentiated vascular SMC in vitro and in injured arteries in vivo.

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

    PubMed

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

    2004-09-01

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

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

    PubMed

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

    2010-07-01

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

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

    PubMed

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

    2007-11-01

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

  14. Gene Expression in Experimental Aortic Coarctation and Repair: Candidate Genes for Therapeutic Intervention?

    PubMed Central

    LaDisa, John F.; Bozdag, Serdar; Olson, Jessica; Ramchandran, Ramani; Kersten, Judy R.; Eddinger, Thomas J.

    2015-01-01

    Coarctation of the aorta (CoA) is a constriction of the proximal descending thoracic aorta and is one of the most common congenital cardiovascular defects. Treatments for CoA improve life expectancy, but morbidity persists, particularly due to the development of chronic hypertension (HTN). Identifying the mechanisms of morbidity is difficult in humans due to confounding variables such as age at repair, follow-up duration, coarctation severity and concurrent anomalies. We previously developed an experimental model that replicates aortic pathology in humans with CoA without these confounding variables, and mimics correction at various times using dissolvable suture. Here we present the most comprehensive description of differentially expressed genes (DEGs) to date from the pathology of CoA, which were obtained using this model. Aortic samples (n=4/group) from the ascending aorta that experiences elevated blood pressure (BP) from induction of CoA, and restoration of normal BP after its correction, were analyzed by gene expression microarray, and enriched genes were converted to human orthologues. 51 DEGs with >6 fold-change (FC) were used to determine enriched Gene Ontology terms, altered pathways, and association with National Library of Medicine Medical Subject Headers (MeSH) IDs for HTN, cardiovascular disease (CVD) and CoA. The results generated 18 pathways, 4 of which (cell cycle, immune system, hemostasis and metabolism) were shared with MeSH ID’s for HTN and CVD, and individual genes were associated with the CoA MeSH ID. A thorough literature search further uncovered association with contractile, cytoskeletal and regulatory proteins related to excitation-contraction coupling and metabolism that may explain the structural and functional changes observed in our experimental model, and ultimately help to unravel the mechanisms responsible for persistent morbidity after treatment for CoA. PMID:26207811

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. 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.

  19. Cyclic strain is a weak inducer of prostacyclin synthase expression in bovine aortic endothelial cells

    NASA Technical Reports Server (NTRS)

    Segurola, R. J. Jr; Oluwole, B.; Mills, I.; Yokoyama, C.; Tanabe, T.; Kito, H.; Nakajima, N.; Sumpio, B. E.

    1997-01-01

    Recent studies indicate that hemodynamic forces such as cyclic strain and shear stress can increase prostacyclin (PGI2) secretion by endothelial cells (EC) but the effect of these forces on prostacyclin synthase (PGIS) gene expression remains unclear and is the focus of this study. Bovine aortic EC were seeded onto type I collagen coated flexible membranes and grown to confluence. The membranes and attached EC were subjected to 10% average strain at 60 cpm (0.5 sec deformation alternating with 0.5 sec relaxation) for up to 5 days. PGIS gene expression was determined by Northern blot analysis and protein level by Western blot analysis. The effect of cyclic strain on the PGIS promoter was determined by the transfection of a 1-kb human PGIS gene promoter construct coupled to a luciferase reporter gene into EC, followed by determination of luciferase activity. PGIS gene expression increased 1.7-fold in EC subjected to cyclic strain for 24 hr. Likewise, EC transfected with a pGL3B-PGIS (-1070/-10) construct showed an approximate 1.3-fold elevation in luciferase activity in EC subjected to cyclic strain for 3, 4, 8, and 12 hr. The weak stimulation of PGIS gene expression by cyclic strain was reflected in an inability to detect alterations in PGIS protein levels in EC subjected to cyclic strain for as long as 5 days. These data suggest that strain-induced stimulation of PGIS gene expression plays only a minor role in the ability of cyclic strain to stimulate PGI2 release in EC. These findings coupled with our earlier demonstration of a requisite addition of exogenous arachidonate in order to observe strain-induced PGI2 release, implicates a mechanism that more likely involves strain-induced stimulation of PGIS activity.

  20. 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.

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

    PubMed

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

    2014-01-01

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

  2. Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells

    PubMed Central

    Trigona, Wendy L.; Mullarky, Isis K.; Cao, Yuzhang; Sordillo, Lorraine M.

    2005-01-01

    Certain selenoproteins such as GPX-1 (glutathione peroxidase-1) and TrxR1 (thioredoxin reductase-1) possess important antioxidant defence functions in vascular endothelial cells. Reduced selenoprotein activity during dietary selenium (Se) deficiency can result in a compensatory increase of other non-Se-dependent antioxidants, such as HO-1 (haem oxygenase-1) that may help to counteract the damaging effects of oxidant stress. However, the role of individual selenoproteins in regulating vascular-derived protective gene responses such as HO-1 is less understood. Using an oxidant stress model based on Se deficiency in BAECs (bovine aortic endothelial cells), we sought to determine whether TrxR1 activity may contribute to the differential regulation of HO-1 expression as a function of altered redox environment. Se-sufficient BAECs up-regulated HO-1 expression following stimulation with the pro-oxidant, 15-HPETE (15-hydroperoxyeicosatetraenoic acid), and levels of this antioxidant inversely correlated with EC apoptosis. While Se-deficient BAECs exhibited higher basal levels of HO-1, it was not up-regulated upon 15-HPETE treatment, which resulted in significantly higher levels of pro-apoptotic markers. Subsequent results showed that HO-1 induction depended on the activity of TrxR1, as proved with chemical inhibitor studies and direct inhibition with TrxR1 siRNA. Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation. These data provide evidence for the involvement of the Trx/TrxR system, in the regulation of HO-1 expression in BAECs during pro-oxidant challenge. PMID:16209660

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

    PubMed Central

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

    2016-01-01

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

  4. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells

    SciTech Connect

    Ziegelstein, Roy C.; Xiong Yali; He Chaoxia; Hu Qinghua . E-mail: qinghuaa@jhmi.edu

    2006-03-31

    Extracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub o}) regulates the functions of many cell types through a G protein-coupled [Ca{sup 2+}]{sub o}-sensing receptor (CaR). Whether the receptor is functionally expressed in vascular endothelial cells is largely unknown. In cultured human aortic endothelial cells (HAEC), RT-PCR yielded the expected 555-bp product corresponding to the CaR, and CaR protein was demonstrated by fluorescence immunostaining and Western blot. RT-PCR also demonstrated the expression in HAEC of alternatively spliced variants of the CaR lacking exon 5. Although stimulation of fura 2-loaded HAEC by several CaR agonists (high [Ca{sup 2+}]{sub o}, neomycin, and gadolinium) failed to increase intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}), the CaR agonist spermine stimulated an increase in [Ca{sup 2+}]{sub i} that was diminished in buffer without Ca{sup 2+} and was abolished after depletion of an intracellular Ca{sup 2+} pool with thapsigargin or after blocking IP{sub 3}- and ryanodine receptor-mediated Ca{sup 2+} release with xestospongin C and with high concentration ryanodine, respectively. Spermine stimulated an increase in DAF-FM fluorescence in HAEC, consistent with NO production. Both the increase in [Ca{sup 2+}]{sub i} and in NO production were reduced or absent in HAEC transfected with siRNA specifically targeted to the CaR. HAEC express a functional CaR that responds to the endogenous polyamine spermine with an increase in [Ca{sup 2+}]{sub i}, primarily due to release of IP{sub 3}- and ryanodine-sensitive intracellular Ca{sup 2+} stores, leading to the production of NO. Expression of alternatively spliced variants of the CaR may result in the absence of a functional response to other known CaR agonists in HAEC.

  5. 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

  6. Synthetic gestagens exert differential effects on arterial thrombosis and aortic gene expression in ovariectomized apolipoprotein E-deficient mice

    PubMed Central

    Freudenberger, T; Deenen, R; Kretschmer, I; Zimmermann, A; Seiler, L F; Mayer, P; Heim, H-K; Köhrer, K; Fischer, J W

    2014-01-01

    Background and Purpose Combined hormone replacement therapy with oestrogens plus the synthetic progestin medroxyprogesterone acetate (MPA) is associated with an increased risk of thrombosis. However, the mechanisms of this pro-thrombotic effect are largely unknown. The purpose of this study was to: (i) compare the pro-thrombotic effect of MPA with another synthetic progestin, norethisterone acetate (NET-A), (ii) determine if MPA's pro-thrombotic effect can be antagonized by the progesterone and glucocorticoid receptor antagonist mifepristone and (iii) elucidate underlying mechanisms by comparing aortic gene expression after chronic MPA with that after NET-A treatment. Experimental Approach Female apolipoprotein E-deficient mice were ovariectomized and treated with placebo, MPA, a combination of MPA + mifepristone or NET-A for 90 days on a Western-type diet. Arterial thrombosis was measured in vivo in a photothrombosis model. Aortic gene expression was analysed using microarrays; GeneOntology and KEGG pathway analyses were conducted. Key Results MPA's pro-thrombotic effects were prevented by mifepristone, while NET-A did not affect arterial thrombosis. Aortic gene expression analysis showed, for the first time, that gestagens induce similar effects on a set of genes potentially promoting thrombosis. However, in NET-A-treated mice other genes with potentially anti-thrombotic effects were also affected, which might counterbalance the effects of the pro-thrombotic genes. Conclusions and Implications The pro-thrombotic effects of synthetic progestins appear to be compound-specific, rather than representing a class effect of gestagens. Furthermore, the different thrombotic responses elicited by MPA and NET-A might be attributed to a more balanced, ‘homeostatic’ gene expression induced in NET-A- as compared with MPA-treated mice. PMID:24923668

  7. Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression.

    PubMed

    Ren, Jun; Liu, Zhenjie; Wang, Qiwei; Giles, Jasmine; Greenberg, Jason; Sheibani, Nader; Kent, K Craig; Liu, Bo

    2016-01-01

    Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P < 0.05). Immunohistochemistry analyses revealed that Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB-mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms. PMID:26483397

  8. Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in arachidonic acid-induced relaxation.

    PubMed

    Aggarwal, Nitin T; Holmes, Blythe B; Cui, Lijie; Viita, Helena; Yla-Herttuala, Seppo; Campbell, William B

    2007-02-01

    Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX) and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15-trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate-limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA (Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected by immunoblotting with an anti-human15-LO-1 antibody, and increased the production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad-15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7 +/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1-treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a-cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is sufficient to increase the production of the vasodilatory HEETA and THETA and enhance the relaxations to AA. This confirms the role of HEETA and THETA as endothelium-derived relaxing factors.

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

    PubMed

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

    2015-09-15

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

  10. A comparison of ENO and TVD schemes

    NASA Technical Reports Server (NTRS)

    Chang, Shih-Hung; Liou, Meng-Sing

    1988-01-01

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

  11. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts

    SciTech Connect

    Wang Zhirong; Chen Yan; Labinskyy, Nazar; Hsieh Tzechen; Ungvari, Zoltan; Wu, Joseph M. . E-mail: Joseph_Wu@nymc.edu

    2006-07-21

    Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol.

  12. Histamine induces activation of protein kinase D that mediates tissue factor expression and activity in human aortic smooth muscle cells.

    PubMed

    Hao, Feng; Wu, Daniel Dongwei; Xu, Xuemin; Cui, Mei-Zhen

    2012-12-01

    Histamine, an inflammatory mediator, has been shown to influence the pathogenesis of vascular wall cells. However, the molecular basis of its influence is not well understood. Our data reveal that histamine markedly induces protein kinase D (PKD) activation in human aortic smooth muscle cells. PKD belongs to a family of serine/threonine protein kinases, and its function in vascular disease is largely unknown. Our data show that histamine-induced PKD phosphorylation is dependent on the activation of histamine receptor 1 and protein kinase C (PKC). To determine the role of PKD in the histamine pathway, we employed a small-interfering RNA approach to downregulate PKD expression and found that PKD1 and PKD2 are key mediators for expression of tissue factor (TF), which is the key initiator of blood coagulation and is important for thrombosis. Our results show that PKD2 predominantly mediates histamine-induced TF expression via the p38 mitogen-activated protein kinase (MAPK) pathway, whereas PKD1 mediates histamine-induced TF expression through a p38 MAPK-independent pathway. We demonstrate that histamine induces TF expression via the PKC-dependent PKD activation. Our data provide the first evidence that PKD is a new component in histamine signaling in live cells and that PKD has a novel function in the histamine signaling pathway leading to gene expression, as evidenced by TF expression. Importantly, our data reveal a regulatory link from histamine to PKD and TF, providing new insights into the mechanisms of coagulation and the development of atherothrombosis.

  13. 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.

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

    PubMed Central

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

    2013-01-01

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

  15. 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.

  16. Cyclooxygenase-2 Expression as a Predictor of Para-Aortic Lymph Node Recurrence in Uterine Cervical Cancer

    SciTech Connect

    Kim, Jun-Sang Li Shengjin; Kim, Jin-Man; Yeo, Seung-Gu; Kim, Ki-Hwan; Cho, Moon-June

    2008-04-01

    Purpose: The overexpression of cyclooxygenase-2 (COX-2) is associated with a worse prognosis and the development of distant metastases in cervical cancer. This matched-pair analysis examined whether COX-2 expression is associated with para-aortic lymph node (PALN) recurrence in uterine cervical cancer treated with radiotherapy (RT). Methods and Materials: For this study, we matched 20 patients with PALN recurrence after definitive or postoperative RT by stage with 20 others who did not have PALN recurrence. Of the 20 patients with PALN recurrence, definitive or postoperative RT was performed in 11 and 9 patients, respectively. COX-2 expression was assessed immunohistochemically using a mouse monoclonal antibody on formalin-fixed paraffin-embedded tumor specimens taken before RT. A logistic regression model was used to predict for PALN recurrence. Results: COX-2 was expressed in 28 (70%) of the 40 patients. The staining intensity was as follows: weak in 19 (47%), moderate in 6 (15%), and strong in 3 (8%) patients. The patients with PALN recurrence had much greater expression of COX-2 (17 patients, 85%) than did the control group (11 patients, 55%; p = 0.04). Strong staining intensity of COX-2 was seen only in the PALN recurrence group. The statistically significant factors associated with PALN recurrence were positive pelvic lymph nodes (odds ratio, 7.61; 95% confidence interval, 1.55-37.37; p = 0.01) and COX-2 expression (odds ratio, 1.47; 95% confidence interval, 1.04-2.09; p = 0.03). Conclusion: Our findings suggest that COX-2 overexpression in the initial tumor tissue might be associated with PALN recurrence after RT in cervical cancer patients.

  17. Mechanisms and Consequences of eNOS Dysfunction in Hypertension

    PubMed Central

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

    2016-01-01

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

  18. 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

  19. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice

    SciTech Connect

    Han, Sung Gu; Eum, Sung Yong; Toborek, Michal; Smart, Eric; Hennig, Bernhard

    2010-07-15

    Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

  20. Expression of kinin B(1) receptor in fresh or cultured rabbit aortic smooth muscle: role of NF-kappa B.

    PubMed

    Sabourin, Thierry; Morissette, Guillaume; Bouthillier, Johanne; Levesque, Luc; Marceau, François

    2002-07-01

    Kinin B(1) receptor (B(1)R) expression and the importance of the transcription factor nuclear factor (NF)-kappa B in this process were evaluated in models based on the rabbit aorta: freshly isolated tissue (postisolation induction) and cultured smooth muscle cells (SMCs). A 3-h incubation of freshly isolated tissues determined a sharp B(1)R mRNA increase (RT-PCR). Coincubation of tissues with a stimulus (interleukin-1 beta, fetal bovine serum, epidermal growth factor, or cycloheximide) further increased mRNA levels. Cultured SMCs possessed a basal population of surface B(1)Rs ([(3)H]Lys-des-Arg(9)-bradykinin binding) that was upregulated by treatments with the same set of stimuli (binding, mRNA, nuclear runon). Pharmacological inhibitors of NF-kappa B (MG-132, BAY 11-7082, dexamethasone) or actinomycin D reduced the postisolation induction of B(1)Rs in fresh aortic tissue (contractility or mRNA) and the cytokine effect on cells (mRNA, binding). NF-kappa B may be a common mediator of various stimuli that increase B(1)R gene transcription in the rabbit aorta, including tissue isolation, but cycloheximide also stabilizes B(1)R mRNA. The SMC models faithfully mimic the in vivo situation with regard to B(1)R regulation.

  1. Serum Amyloid A Promotes E-Selectin Expression via Toll-Like Receptor 2 in Human Aortic Endothelial Cells

    PubMed Central

    2016-01-01

    Periodontitis is a chronic inflammatory disease that affects the periodontium. Recent studies suggest an association between periodontal and cardiovascular diseases. However, the detailed molecular mechanism is unknown. A previous study has demonstrated that experimental periodontitis induces serum amyloid A (SAA) in the liver and peripheral blood of ApoE-deficient mice as an atherosclerosis model. SAA is an acute-phase protein that affects systemic inflammation. The aim of this study is to investigate the atherosclerosis-onset mechanism using human aortic endothelial cells (HAECs) stimulated by SAA in vitro. Atherosclerosis PCR array and qPCR analyses showed upregulation of adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in HAECs upon SAA stimulation. In addition, the results demonstrated that Toll-like receptor, TLR2, could serve as an important receptor of SAA in HAECs. Furthermore, small interfering RNA (siRNA) against TLR2 inhibited the upregulation of adhesion molecules in HAECs stimulated by SAA. Our results suggest that SAA stimulates the expression of adhesion molecules via TLR2. SAA could be an important molecule for atherosclerosis induced by periodontal disease. PMID:27799725

  2. Rabbit aortic smooth muscle cells express inducible macrophage scavenger receptor messenger RNA that is absent from endothelial cells.

    PubMed Central

    Bickel, P E; Freeman, M W

    1992-01-01

    Scavenger receptors mediate uptake of modified low density lipoproteins by macrophages. The accumulation of lipids via this process is thought to lead to foam cell formation in developing atherosclerotic plaques. Smooth muscle cells, which can also be converted to foam cells in vivo, have not been shown to express the same scavenger receptor previously cloned in macrophages. We report the cloning of two cDNAs that encode type I and type II scavenger receptors isolated from rabbit smooth muscle cells. The deduced protein sequences of these isolates are highly homologous to the scavenger receptors previously isolated from macrophages. Treatment of smooth muscle cells with phorbol esters induced a marked increase in scavenger receptor mRNA and a fivefold increase in receptor degradation activity. Rabbit venous endothelial cells in primary culture and a bovine aortic endothelial cell line had no detectable scavenger receptor mRNA, despite having scavenger receptor degradation activity. The latter finding suggests that endothelial cells may possess a scavenger receptor which is structurally distinct from that found in macrophages and smooth muscle cells. The isolation of cDNAs encoding the rabbit scavenger receptor should prove useful for in vitro and in vivo studies that employ the rabbit as a model of human atherosclerosis. Images PMID:1401078

  3. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells

    SciTech Connect

    Majesky, M.W.; Benditt, E.P.; Schwartz, S.M.

    1988-03-01

    Cultured arterial smooth muscle cells (SMC) can produce platelet-derived growth factor (PDGF)-like molecules. This property raises the possibility that SMC-derived PDGFs function as autocrine/paracrine regulators in the formation and maintenance of the artery wall. In this study the authors have asked if levels of mRNAs directing synthesis of PDFG are modulated in aortic SMC during postnatal development. The authors report here that genes encoding PDGF A- and B-chain precursors are expressed at similar low levels in intact aortas from newborn and adult rats. Marked differences in regulation of transcript abundance of these genes were revealed when aortic SMC were grown in cell culture. PDGF B-chain transcripts accumulated in passaged newborn rat SMC but not adult rat SMC, whereas PDGF A-chain RNA was found in comparable amounts in SMC from both age groups. Similarly, SMC from newborn rats secreted at least 60-fold more PDGF-like activity into conditioned medium than did adult rat SMC. These results show that PDGF A- and B-chain genes are transcribed in the normal rat aorta and provide evidence for age-related change in the control of PDGF B-chain gene expression in aortic SMC. Independent regulation of transcript levels in cultured SMC leaves open the possibility that PDGFs of different composition (AA, AB, BB) play different roles in normal function of the artery wall.

  4. Gene silencing of endothelial von Willebrand Factor attenuates angiotensin II-induced endothelin-1 expression in porcine aortic endothelial cells

    PubMed Central

    Dushpanova, Anar; Agostini, Silvia; Ciofini, Enrica; Cabiati, Manuela; Casieri, Valentina; Matteucci, Marco; Del Ry, Silvia; Clerico, Aldo; Berti, Sergio; Lionetti, Vincenzo

    2016-01-01

    Expression of endothelin (ET)-1 is increased in endothelial cells exposed to angiotensin II (Ang II), leading to endothelial dysfunction and cardiovascular disorders. Since von Willebrand Factor (vWF) blockade improves endothelial function in coronary patients, we hypothesized that targeting endothelial vWF with short interference RNA (siRNA) prevents Ang II-induced ET-1 upregulation. Nearly 65 ± 2% silencing of vWF in porcine aortic endothelial cells (PAOECs) was achieved with vWF-specific siRNA without affecting cell viability and growth. While showing ET-1 similar to wild type cells at rest, vWF-silenced cells did not present ET-1 upregulation during exposure to Ang II (100 nM/24 h), preserving levels of endothelial nitric oxide synthase activity similar to wild type. vWF silencing prevented AngII-induced increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity and superoxide anion (O2−) levels, known triggers of ET-1 expression. Moreover, no increase in O2− or ET-1 levels was found in silenced cells treated with AngII or NOX-agonist phorbol ester (PMA 5 nM/48 h). Finally, vWF was required for overexpression of NOX4 and NOX2 in response to AngII and PMA. In conclusion, endothelial vWF knockdown prevented Ang II-induced ET-1 upregulation through attenuation of NOX-mediated O2− production. Our findings reveal a new role of vWF in preventing of Ang II-induced endothelial dysfunction. PMID:27443965

  5. 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

  6. The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region.

    PubMed

    Kreikemeyer, Bernd; Nakata, Masanobu; Köller, Thomas; Hildisch, Hendrikje; Kourakos, Vassilios; Standar, Kerstin; Kawabata, Shigetada; Glocker, Michael O; Podbielski, Andreas

    2007-12-01

    Many Streptococcus pyogenes (group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from Streptococcus suis). In a serotype-specific fashion, this ralp3 epf gene block is integrated, most likely via transposition, into the eno sagA virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the eno ralp3 epf sagA (ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known

  7. 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 ...

  8. 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, ...

  9. Double aortic arch

    MedlinePlus

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

  10. Aortic Aneurysm

    MedlinePlus

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

  11. 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

  12. 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

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

    PubMed

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

    2015-11-01

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

  14. The role of eNOS in the migration and proliferation of bone-marrow derived endothelial progenitor cells and in vitro angiogenesis.

    PubMed

    Lu, Aizhen; Wang, Libo; Qian, Liling

    2015-04-01

    The role of endothelial nitric oxide synthase (eNOS) in the activities of endothelial progenitor cells (EPCs) including migration, proliferation, and tube formation in vitro was investigated. EPCs were obtained from rat bone mononuclear cells by culturing for 7-10 days in EGM-2MV and identified by their capacity for FITC-UEA-1 binding and acetylated low-density lipoprotein (Dil-ac-LDL) intake using fluorescence microscopy. Migration, proliferation and tube formation activities were assessed in the presence or absence of N(ω)-nitro-L-argininemethylester (L-NAME), an eNOS inhibitor. mRNA and protein expression of CXCR4, CXCR7, VEGFR2, and eNOS were detected by real-time PCR and western blotting in the presence or absence of L-NAME. Nitric oxide production was detected by nitrate reductase in the presence or absence of L-NAME. Typical spindle-shaped cells appeared on the 7(th)-10(th) day and confluence reached about 80%. The percentage of FITC-UEA-1 and Dil-ac-LDL double-stained cells was about 85%. Cell migration, proliferation, and tube formation were significantly weakened after eNOS was inhibited (P < 0.05), and the expressions of CXCR4 and eNOS were significantly reduced (P < 0.05, respectively), but there was little change in CXCR7 and VEGFR2. NO production was dramatically decreased after eNOS was inhibited (P < 0.05). In summary, L-NAME significantly reduced the expression of eNOS and NO production by EPCs and inhibited migration, proliferation and tube formation by these cells, suggesting that eNOS affects EPC activities; CXCR4 may be implicated in the action of eNOS.

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

    PubMed Central

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

    2008-01-01

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

  16. [Aortic aneurysm].

    PubMed

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

    2013-01-01

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

  17. 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

  18. Atrial natriuretic peptide inhibits the expression of tissue factor and plasminogen activator inhibitor 1 induced by angiotensin II in cultured rat aortic endothelial cells.

    PubMed

    Yoshizumi, M; Tsuji, H; Nishimura, H; Kasahara, T; Sugano, T; Masuda, H; Nakagawa, K; Nakahara, Y; Kitamura, H; Yamada, K; Yoneda, M; Sawada, S; Nakagawa, M

    1998-03-01

    The pharmacological characteristics of atrial natriuretic peptide (ANP), such as natriuresis, vasodilation, or suppression of smooth muscle cell proliferation, are well investigated. However, this is the first study to report its role on blood coagulation and fibrinolysis mediated by vascular endothelial cells. In this study, the effects of ANP on the enhanced expression of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in cultured rat aortic endothelial cells (RAECs) were examined. The expressions of TF and PAI-1 mRNA were detected by northern blotting methods. The activities of TF on the surface of RAECs and PAI-1 in the culture media were measured by chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang II in a concentration-dependent manner. This suppression was accompanied by the decreased activities of TF and PAI-1.

  19. 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

  20. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells

    SciTech Connect

    Hossain, Ekhtear; Ota, Akinobu; Karnan, Sivasundaram; Damdindorj, Lkhagvasuren; Takahashi, Miyuki; Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. - Highlights: • Sodium arsenite (SA) increases LOX-1 expression in mouse aortic endothelial cells. • SA enhances cellular uptake of oxidized LDL in dose-dependent manner. • SA-induced ROS generation enhances phosphorylation of NF-κB. • SA upregulates LOX-1 expression through ROS-activated NF-κB signaling pathway.

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

    PubMed Central

    Wang, Chunmao; Qian, Xiangyang; Sun, Xiaogang

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2016-08-02

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

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

    PubMed

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

    2016-01-01

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

  6. Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from diabetic eNOS knockout mice.

    PubMed

    Takahashi, Takamune; Harris, Raymond C

    2014-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study. PMID:25371905

  7. Nitric oxide up-regulates endothelial expression of angiotensin II type 2 receptors.

    PubMed

    Dao, Vu Thao-Vi; Medini, Sawsan; Bisha, Marion; Balz, Vera; Suvorava, Tatsiana; Bas, Murat; Kojda, Georg

    2016-07-15

    Increasing vascular NO levels following up-regulation of endothelial nitric oxide synthase (eNOS) is considered beneficial in cardiovascular disease. Whether such beneficial effects exerted by increased NO-levels include the vascular renin-angiotensin system remains elucidated. Exposure of endothelial cells originated from porcine aorta, mouse brain and human umbilical veins to different NO-donors showed that expression of the angiotensin-II-type-2-receptor (AT2) mRNA and protein is up-regulated by activation of soluble guanylyl cyclase, protein kinase G and p38 mitogen-activated protein kinase without changing AT2 mRNA stability. In mice, endothelial-specific overexpression of eNOS stimulated, while chronic treatment with the NOS-blocker l-nitroarginine inhibited AT2 expression. The NO-induced AT2 up-regulation was associated with a profound inhibition of angiotensin-converting enzyme (ACE)-activity. In endothelial cells this reduction of ACE-activity was reversed by either the AT2 antagonist PD 123119 or by inhibition of transcription with actinomycin D. Furthermore, in C57Bl/6 mice an acute i.v. bolus of l-nitroarginine did not change AT2-expression and ACE-activity suggesting that inhibition of ACE-activity by endogenous NO is crucially dependent on AT2 protein level. Likewise, three weeks of either voluntary or forced exercise training increased AT2 expression and reduced ACE-activity in C57Bl/6 but not in mice lacking eNOS suggesting significance of this signaling interaction for vascular physiology. Finally, aortic AT2 expression is about 5 times greater in female as compared to male C57Bl/6 and at the same time aortic ACE activity is reduced in females by more than 50%. Together these findings imply that endothelial NO regulates AT2 expression and that AT2 may regulate ACE-activity. PMID:27235748

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

    PubMed

    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

  9. 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

  10. 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

  11. 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 ...

  12. Actin isoform and alpha 1B-adrenoceptor gene expression in aortic and coronary smooth muscle is influenced by cyclical stretch.

    PubMed

    Lundberg, M S; Sadhu, D N; Grumman, V E; Chilian, W M; Ramos, K S

    1995-09-01

    The occurrence of vascular domains with specific biological and pharmacological characteristics suggests that smooth muscle cells in different arteries may respond differentially to a wide range of environmental stimuli. To determine if some of these vessel-specific differences may be attributable to mechano-sensitive gene regulation, the influence of cyclical stretch on the expression of actin isoform and alpha 1B-adrenoceptor genes was examined in aortic and coronary smooth muscle cells. Cells were seeded on an elastin substrate and subjected to maximal stretching (24% elongation) and relaxation cycles at a frequency of 120 cycles/min in a Flexercell strain unit for 72 h. Total RNA was extracted and hybridized to radiolabeled cDNA probes to assess gene expression. Stretch caused a greater reduction of actin isoform mRNA levels in aortic smooth muscle cells as compared to cells from the coronary artery. Steady-state mRNA levels of alpha 1B-adrenoceptor were also decreased by cyclical stretch in both cell types but the magnitude of the response was greater in coronary smooth muscle cells. No changes in alpha 1B-adrenoceptor or beta/gamma-actin steady-state mRNA levels were observed in H4IIE cells, a nonvascular, immortalized cell line. The relative gene expression of heat shock protein 70 was not influenced by the cyclic stretch regimen in any of these cell types. These results suggest that stretch may participate in the regulation of gene expression in vascular smooth muscle cells and that this response exhibits some degree of cell-specificity.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. eNOS Genetic Polymorphisms and Cancer Risk

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

  19. Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

    SciTech Connect

    Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee; Lee, Ji-Won; Hwangbo, Mi Hyang; Kim, Cheorl-Ho; Lee, In-Seon . E-mail: inseon@kmu.ac.kr

    2006-12-08

    Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPK signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.

  20. Leptin stimulates endothelin-1 expression via extracellular signal-regulated kinase by epidermal growth factor receptor transactivation in rat aortic smooth muscle cells.

    PubMed

    Chao, Hung-Hsing; Hong, Hong-Jye; Liu, Ju-Chi; Lin, Jia-Wei; Chen, Yen-Ling; Chiu, Wen-Ta; Wu, Chieh-Hsi; Shyu, Kou-Gi; Cheng, Tzu-Hurng

    2007-11-14

    Obesity is a major risk factor for the development of hypertension. Recent studies have suggested that leptin, a 167-amino acid peptide hormone produced by white adipose tissue, is related to the pathogenesis of obesity-related hypertension. However, the signaling mechanisms underlying the effects of leptin remain to be extensively examined. In this study, we found that leptin induced extracellular signal-regulated kinase phosphorylation and endothelin-1 expression in rat aortic smooth muscle cells. Both PD98059 and U0126, inhibitors of the upstream activator of mitogen-activated protein kinase kinase, inhibited augmentation of endothelin-1 expression stimulated with leptin. Leptin induced significant tyrosine phosphorylation of epidermal growth factor receptor, which was significantly attenuated by two inhibitors, an epidermal growth factor receptor tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This indicates that the pathway of epidermal growth factor receptor transactivation induced by leptin is dependent on proteolytically released epidermal growth factor receptor ligands. Pretreatment of cells with AG1478 significantly reduced the degree of phosphorylation of extracellular signal-regulated kinase and endothelin-1 expression. Our results reveal that epidermal growth factor receptor transactivation is involved in the leptin signaling pathway in vascular smooth muscle cells, which may be related to the increased risk of hypertension and other cardiovascular diseases in obese subjects. PMID:17678888

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

    PubMed

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

    2006-10-01

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

  2. 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

  3. Inhibitory Role of Notch1 in Calcific Aortic Valve Disease

    PubMed Central

    Koenig, Sara N.; Nichols, Haley A.; Galindo, Cristi L.; Garner, Harold R.; Merrill, Walter H.; Hinton, Robert B.; Garg, Vidu

    2011-01-01

    Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism. PMID:22110751

  4. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.

    PubMed Central

    Hernández-Perera, O; Pérez-Sala, D; Navarro-Antolín, J; Sánchez-Pascuala, R; Hernández, G; Díaz, C; Lamas, S

    1998-01-01

    Endothelial dysfunction associated with atherosclerosis has been attributed to alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to ameliorate endothelial function. However, the physiological basis of this observation is largely unknown. We investigated the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and protein levels in bovine aortic endothelial cells. These agents inhibited pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This inhibitory effect was maintained in the presence of oxidized LDL (1-50 microg/ml). No significant modification of pre-proET-1 mRNA half-life was observed. In addition, mevalonate, but not cholesterol, reversed the statin-mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native LDL had no effect. Statins were able to prevent the inhibitory action exerted by oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence vascular tone by modulating the expression of endothelial vasoactive factors. PMID:9637705

  5. 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

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

    PubMed Central

    Song, Kai; Shang, Zheng-Jun

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. Balloon aortic valvuloplasty.

    PubMed

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

    1997-01-01

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

  9. Aortic Annular Enlargement during Aortic Valve Replacement

    PubMed Central

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

    2016-01-01

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

  10. Both common and specialty mushrooms inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells in a pro-inflammatory environment

    PubMed Central

    2010-01-01

    Background Cardiovascular disease (CVD) is a leading cause of mortality in the United States as well as globally. Epidemiological studies show that regular fruit and vegetable consumption reduces CVD risk, in part, due to antioxidant activity and immunomodulation since oxidative stress and inflammation are features of atherogenesis. Accumulating evidence also shows that dietary fungi, viz., mushrooms, can protect against chronic disease by altering inflammatory environments such as those associated with CVD although most research has focused on specialty mushrooms. In this study, we tested the ability of both common and specialty mushrooms to inhibit cellular processes associated with CVD. Methods Human aortic endothelial cells (HAEC) were incubated overnight with control media with dimethylsulfoxide (DMSO) vehicle (1% v/v) or containing DMSO extracts of whole dehydrated mushrooms (0.1 mg/mL), which included Agaricus bisporus (white button and crimini), Lentinula edodes (shiitake), Pleurotus ostreatus (oyster), and Grifola frondosa (maitake). Monolayers were subsequently washed and incubated with medium alone or containing the pro-inflammatory cytokine IL-1β (5 ng/mL) for 6 h to upregulate pro-atherosclerotic adhesion molecules (AM). AM expression was assayed by ELISA and binding of U937 human monocytes pre-loaded with fluorescent dye was determined. Results White button mushrooms consistently reduced (p < 0.05) VCAM-1, ICAM-1, and E-selectin-1 expression, whereas other test mushrooms significantly modulated AM expression singly, collectively, or combinatorially. All mushrooms, however, significantly reduced binding of monocytes to both quiescent and cytokine-stimulated monolayers. Conclusion These data provide evidence that dietary mushrooms can inhibit cellular processes such as adhesion molecule expression and ultimate binding of monocytes to the endothelium under pro-inflammatory conditions, which are associated with CVD. As a result, these findings support

  11. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells.

    PubMed

    Hossain, Ekhtear; Ota, Akinobu; Karnan, Sivasundaram; Damdindorj, Lkhagvasuren; Takahashi, Miyuki; Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. PMID:24145059

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. Role of muscular eNOS in skeletal arteries: Endothelium-independent hypoxic vasoconstriction of the femoral artery is impaired in eNOS-deficient mice.

    PubMed

    Kim, Hae Jin; Yoo, Hae Young; Lin, Hai Yue; Oh, Goo Taeg; Zhang, Yin Hua; Kim, Sung Joon

    2016-09-01

    We previously reported that hypoxia augments α-adrenergic contraction (hypoxic vasoconstriction, HVC) of skeletal arteries in rats. The underlying mechanism may involve hypoxic inhibition of endothelial nitric oxide synthase (eNOS) expressed in skeletal arterial myocytes (16). To further explore the novel role of muscular eNOS in the skeletal artery, we compared HVC in femoral arteries (FAs) from eNOS knockout (KO) mice with that from wild-type (WT) and heterozygous (HZ) mice. Immunohistochemical assays revealed that, in addition to endothelia, eNOS is also expressed in the medial layer of FAs, albeit at a much lower level. However, the medial eNOS signal was not evident in HZ FAs, despite strong expression in the endothelium; similar observations were made in WT carotid arteries (CAs). The amplitude of contraction induced by 1 μM phenylephrine (PhE) was greater in HZ than in WT FAs. Hypoxia (3% Po2) significantly augmented PhE-induced contraction in WT FAs but not in HZ or KO FAs. No HVC was observed in PhE-pretreated WT CAs. The NOS inhibitor nitro-l-arginine methyl ester (0.1 mM) also augmented PhE contraction in endothelium-denuded WT FAs but not in WT CAs. Inhibitors specific to neuronal NOS and inducible NOS did not augment PhE-induced contraction of WT FAs. NADPH oxidase 4 (NOX4) inhibitor (GKT137831, 5 μM), but not NOX2 inhibitor (apocynin, 100 μM), suppressed HVC. Consistent with the role of reactive oxygen species (ROS), HVC was also inhibited by pretreatment with tiron or polyethylene glycol-catalase. Taken together, these data suggest that the eNOS expressed in smooth muscle cells in FAs attenuates α-adrenergic vasoconstriction; this suppression is alleviated under hypoxia, which potentiates vasoconstriction in a NOX4/ROS-dependent mechanism. PMID:27486092

  15. Abdominal Aortic Aneurysms: Treatments

    MedlinePlus

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

  16. 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

  17. Fangchinoline inhibits rat aortic vascular smooth muscle cell proliferation and cell cycle progression through inhibition of ERK1/2 activation and c-fos expression.

    PubMed

    Zhang, Yong-He; Fang, Lian-Hua; Ku, Bao-Shan

    2003-11-01

    Fangchinoline (FAN; a plant alkaloid isolated from Stephania tetrandrae) is a nonspecific Ca(2+) channel blocker. The objective of the present study was to investigate the effect of FAN on the growth factor-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). FAN significantly inhibited both 5% fetal bovine serum (FBS)- and 50ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation, [3H]thymidine incorporation into DNA and phosphorylation of extracellular signal-regulated kinase 1/2. In accordance with these findings, FAN revealed blocking of the FBS-inducible progression through G(0)/G(1) to S phase of the cell cycle in synchronized cells and caused a 62% decrease in the early elevation of c-fos expression induced after 5% FBS addition. Furthermore, significant antiproliferative activity of FAN is observed at concentrations below those required to achieve significant inhibition of Ca(2+) channels by FAN. These results suggest that FAN reduced both FBS- and PDGF-BB-induced RASMCs proliferation by perturbing cell cycle progression. This antiproliferative effect of FAN is dependent on the MAP kinase pathway, but cannot be limited to its Ca(2+) modulation. PMID:14563495

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

    PubMed Central

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

    2010-01-01

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

  19. Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis.

    PubMed

    Bunjevacki, Vera; Maksimovic, Nela; Jekic, Biljana; Milic, Vera; Lukovic, Ljiljana; Novakovic, Ivana; Damjanov, Nemanja; Radunovic, Goran; Damnjanovic, Tatjana

    2016-04-01

    Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction-restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course. PMID:26612436

  20. Aortic and Carotid Arterial Stiffness and Epigenetic Regulator Gene Expression Changes Precede Blood Pressure Rise in Stroke-Prone Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Herrera, Victoria L.; Decano, Julius L.; Giordano, Nicholas; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2014-01-01

    Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation. PMID:25229245

  1. Stimulation of activin A expression in rat aortic smooth muscle cells by thrombin and angiotensin II correlates with neointimal formation in vivo.

    PubMed Central

    Pawlowski, J E; Taylor, D S; Valentine, M; Hail, M E; Ferrer, P; Kowala, M C; Molloy, C J

    1997-01-01

    Vasoactive GTP-binding protein-coupled receptor agonists (e.g., angiotensin II [AII] and alpha-thrombin) stimulate the production of mitogenic factors from vascular smooth muscle cells. In experiments to identify mitogens secreted from AII- or alpha-thrombin-stimulated rat aortic smooth muscle (RASM) cells, neutralizing antibodies directed against several growth factors (e.g., PDGF and basic fibroblast growth factor [basic FGF]) failed to inhibit the mitogenic activity of conditioned media samples derived from the cells. In this report, we found that polyclonal neutralizing antibodies directed against purified human placental basic FGF reduced the mitogenic activity of AII-stimulated RASM cell-conditioned media and in immunoblot experiments identified a 26-kD protein (14 kD under reducing conditions) that was distinct from basic FGF. After purification from RASM cell-conditioned medium, amino acid sequence analysis identified the protein as activin A, a member of the TGF-beta superfamily. Increased activin A expression was observed after treatment of the RASM cells with AII, alpha-thrombin, and the protein kinase C agonist PMA. In contrast, PDGF-BB or serum caused only a minor induction of this protein. Although activin A alone only weakly stimulated RASM cell DNA synthesis, it demonstrated a potent comitogenic effect in combination with either EGF or heparin-binding EGF-like growth factor in the RASM cells, increasing DNA synthesis by up to fourfold. Furthermore, in a rat carotid injury model, activin A mRNA was upregulated within 6 h after injury followed by increases in immunoreactive protein detected in the expanding neointima 7 and 14 d later. Taken together, these results indicate that activin A is a vascular smooth muscle cell-derived factor induced by vasoactive agonists that may, either alone or in combination with other vascular derived growth factors, have a role in neointimal formation after arterial injury. PMID:9239411

  2. β-Cyclodextrins Decrease Cholesterol Release and ABC-Associated Transporter Expression in Smooth Muscle Cells and Aortic Endothelial Cells

    PubMed Central

    Coisne, Caroline; Hallier-Vanuxeem, Dorothée; Boucau, Marie-Christine; Hachani, Johan; Tilloy, Sébastien; Bricout, Hervé; Monflier, Eric; Wils, Daniel; Serpelloni, Michel; Parissaux, Xavier; Fenart, Laurence; Gosselet, Fabien

    2016-01-01

    Atherosclerosis is an inflammatory disease that leads to an aberrant accumulation of cholesterol in vessel walls forming atherosclerotic plaques. During this process, the mechanism regulating complex cellular cholesterol pools defined as the reverse cholesterol transport (RCT) is altered as well as expression and functionality of transporters involved in this process, namely ABCA1, ABCG1, and SR-BI. Macrophages, arterial endothelial and smooth muscle cells (SMCs) have been involved in the atherosclerotic plaque formation. As macrophages are widely described as the major cell type forming the foam cells by accumulating intracellular cholesterol, RCT alterations have been poorly studied at the arterial endothelial cell and SMC levels. Amongst the therapeutics tested to actively counteract cellular cholesterol accumulation, the methylated β-cyclodextrin, KLEPTOSE® CRYSMEβ, has recently shown promising effects on decreasing the atherosclerotic plaque size in atherosclerotic mouse models. Therefore we investigated in vitro the RCT process occurring in SMCs and in arterial endothelial cells (ABAE) as well as the ability of some modified β-CDs with different methylation degree to modify RCT in these cells. To this aim, cells were incubated in the presence of different methylated β-CDs, including KLEPTOSE® CRYSMEβ. Both cell types were shown to express basal levels of ABCA1 and SR-BI whereas ABCG1 was solely found in ABAE. Upon CD treatments, the percentage of membrane-extracted cholesterol correlated to the methylation degree of the CDs independently of the lipid composition of the cell membranes. Decreasing the cellular cholesterol content with CDs led to reduce the expression levels of ABCA1 and ABCG1. In addition, the cholesterol efflux to ApoA-I and HDL particles was significantly decreased suggesting that cells forming the blood vessel wall are able to counteract the CD-induced loss of cholesterol. Taken together, our observations suggest that methylated

  3. Central Role of eNOS in the Maintenance of Endothelial Homeostasis

    PubMed Central

    Rodriguez-Mateos, Ana; Kelm, Malte

    2015-01-01

    Abstract Significance: Disruption of endothelial function is considered a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase (eNOS) is a central regulator of cellular function that is important to maintain endothelial homeostasis. Recent Advances: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue's demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells (ECs) and attraction of circulating angiogenic cells (CAC), both of which support repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of NO-dependent vasodilation, whereas EMP are upcoming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with NO representing a central signaling molecule. Critical Issues: Improvements of reproducibility and observer independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research. Future Directions: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance. Antioxid. Redox Signal. 22, 1230–1242. PMID:25330054

  4. 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

  5. Para-aortic lymphocyst.

    PubMed

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

    1980-10-15

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

  6. 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

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

    PubMed Central

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

    2016-01-01

    Toxoplasma gondii is an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage of T. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified from Escherichia coli with pET-30a(+) expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+ T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8 ± 2.77 d), rTgENO2 (7.4 ± 1.81 d), and rTgTrxLp + rTgENO2 (8.38 ± 4.57 d) proteins showed significantly longer survival time than those that received Freund's adjuvant (6.78 ± 2.08 d) and PBS (6.38 ± 4.65 d) (χ2 = 9.687, df = 4, P = 0.046). The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronic T. gondii infection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis. PMID:27803923

  8. 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

  9. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease.

    PubMed

    Cortese-Krott, Miriam M; Rodriguez-Mateos, Ana; Sansone, Roberto; Kuhnle, Gunter G C; Thasian-Sivarajah, Sivatharsini; Krenz, Thomas; Horn, Patrick; Krisp, Christoph; Wolters, Dirk; Heiß, Christian; Kröncke, Klaus-Dietrich; Hogg, Neil; Feelisch, Martin; Kelm, Malte

    2012-11-15

    A nitric oxide synthase (NOS)-like activity has been demonstrated in human red blood cells (RBCs), but doubts about its functional significance, isoform identity and disease relevance remain. Using flow cytometry in combination with the nitric oxide (NO)-imaging probe DAF-FM we find that all blood cells form NO intracellularly, with a rank order of monocytes > neutrophils > lymphocytes > RBCs > platelets. The observation of a NO-related fluorescence within RBCs was unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive normoxic NO formation was abolished by NOS inhibition and intracellular NO scavenging, confirmed by laser-scanning microscopy and unequivocally validated by detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Using immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we further demonstrate that human RBCs contain an endothelial NOS (eNOS) that converts L-(3)H-arginine to L-(3)H-citrulline in a Ca(2+)/calmodulin-dependent fashion. Moreover, in patients with coronary artery disease, red cell eNOS expression and activity are both lower than in age-matched healthy individuals and correlate with the degree of endothelial dysfunction. Thus, human RBCs constitutively produce NO under normoxic conditions via an active eNOS isoform, the activity of which is compromised in patients with coronary artery disease.

  10. 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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2009-10-01

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

  13. 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…

  14. 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

  15. Long Telomeres in Blood Leukocytes Are Associated with a High Risk of Ascending Aortic Aneurysm

    PubMed Central

    Huusko, Tuija J.; Santaniemi, Merja; Kakko, Sakari; Taskinen, Panu; Ukkola, Olavi; Kesäniemi, Y. Antero; Savolainen, Markku J.; Salonurmi, Tuire

    2012-01-01

    Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm. PMID:23209831

  16. PI3K/AKT signaling pathway plays a role in enhancement of eNOS activity by recombinant human angiotensin converting enzyme 2 in human umbilical vein endothelial cells

    PubMed Central

    Zhang, Yan; Wang, Shi-Jie; Han, Zhen-Hua; Li, Yong-Qin; Xue, Jia-Hong; Gao, Deng-Feng; Wu, Xiao-San; Wang, Cong-Xia

    2014-01-01

    The aim of this study was to investigate the effect of PI3K/AKT signaling pathway in the activity of recombinant human angiotensin converting enzyme 2 (rhACE2) promoted the activity of endothelial nitric oxide synthase (eNOS). The human umbilical vein endothelial cells (HUVEC) were cultured in vitro. Then treated with Ang II (1×10-6 mol/L) for 24 h. The rhACE2 (100 μmol/L) was added and incubated for 5, 10, 15, 30, 60 min respectively which was based on Ang II intervention. The effect of rhACE2 on phosphorylation eNOS level was also observed in the presence of LY294002 (10 μmol/L) (PI3K/AKT inhibitors). Griess reagent method was applied to measure NO contents in cell culture supernatant, RT-PCR to detect the expression of eNOSmRNA in HUVEC, and Western blot to detect the expression of eNOS and phosphorylated eNOS. In Ang II intervention group, NO contents were significantly lower than control group (P < 0.05). Through rhACE2 treatment, the NO contents in cell culture medium and the expression level of phosphorylated eNOS were significantly higher than in Ang II intervention group (P < 0.05), but eNOSmRNA and non-phosphorylated eNOS protein expression level showed no significant difference (P > 0.05). After HUVEC was intervened by PI3K/AKT pathway inhibitor LY294002, the expression level of phosphorylated eNOS was significantly lower than that in the rhACE2 30 min treatment group (P < 0.05). rhACE2 may reduce the activity of Ang II inhibited endothelial cell eNOS, which can be blocked by PI3K/AKT pathway inhibitor LY294002, suggesting PI3K/AKT signaling pathway plays an important role in rhACE2’s promotion of the activity of endothelial cell eNOS. PMID:25550859

  17. An ethanol root extract of Cynanchum wilfordii containing acetophenones suppresses the expression of VCAM-1 and ICAM-1 in TNF-α-stimulated human aortic smooth muscle cells through the NF-κB pathway.

    PubMed

    Koo, Hyun Jung; Sohn, Eun-Hwa; Pyo, Suhkneung; Woo, Han Goo; Park, Dae Won; Ham, Young-Min; Jang, Seon-A; Park, Soo-Yeong; Kang, Se Chan

    2015-04-01

    The root of Cynanchum wilfordii (C. wilfordii) contains several biologically active compounds which have been used as traditional medicines in Asia. In the present study, we evaluated the anti-inflammatory effects of an ethanol root extract of C. wilfordii (CWE) on tumor necrosis factor (TNF)-α-stimulated human aortic smooth muscle cells (HASMCs). The inhibitory effects of CWE on vascular cell adhesion molecule (VCAM)-1 expression under an optimum extraction condition were examined. CWE suppressed the expression of VCAM-1 and ICAM-1 and the adhesion of THP-1 monocytes to the TNF-α-stimulated HASMCs. Consistent with the in vitro observations, CWE inhibited the aortic expression of ICAM-1 and VCAM-1 in atherogenic diet-fed mice. CWE also downregulated the expression of nuclear factor-κB (NF-κB p65) and its uclear translocation in the stimulated HASMCs. In order to identify the active components in CWE, we re-extracted CWE using several solvents, and found that the ethyl acetate fraction was the most effective in suppressing the expression of VCAM-1 and ICAM-1. Four major acetophenones were purified from the ethyl acetate fraction, and two components, p-hydroxyacetophenone and cynandione A, potently inhibited the expression of ICAM-1 and VCAM-1 in the stimulated HASMCs. We assessed and determined the amounts of these two active components from CWE, and our results suggested that the root of C. wilfordii and its two bioactive acetophenones may be used for the prevention and treatment of atherosclerosis and vascular inflammatory diseases. PMID:25716870

  18. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    PubMed

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future.

  19. 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

  20. 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

  1. 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

  2. Erythropoietin Reverses Sepsis-Induced Vasoplegia to Norepinephrine Through Preservation of α1D-Adrenoceptor mRNA Expression and Inhibition of GRK2-Mediated Desensitization in Mouse Aorta.

    PubMed

    Kandasamy, Kannan; Choudhury, Soumen; Singh, Vishakha; Addison, M Pule; Darzi, Sazad Ahmad; Kasa, Jaya Kiran; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Kumar, Tarun; Sultan, Faheem; Singh, Thakur Uttam; Parida, Subhashree; Mishra, Santosh Kumar

    2016-01-01

    We investigated the effect of erythropoietin (EPO) posttreatment on survival time and vascular functions in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture. After 20 ± 2 hours of sepsis, thoracic aorta was isolated for assessing its reactivity to norepinephrine (NE) and acetylcholine (ACh). We also measured the tissue nitric oxide (NO) level, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), G protein-coupled receptor kinase 2 (GRK2), and α1D adrenoceptor messenger RNA (mRNA)/protein expression. In septic mice, EPO moderately improved the survival time from 19.68 ± 0.75 to 34.7 ± 3.2 hours. Sepsis significantly decreased the aortic contractile response to NE along with reduced α1D mRNA and protein expression. Erythropoietin significantly preserved the α1D receptor expression and restored NE-induced contractions to control levels in septic mice. Further, it attenuated the aortic α1D receptor desensitization in sepsis which was evident from reduced GRK2 mRNA expression. Accordingly, a selective GRK2 inhibitor markedly restored the contractile responses to NE in sepsis. Erythropoietin treatment attenuated iNOS mRNA expression and iNOS-induced overproduction of NO, but improved endothelium-dependent relaxation to ACh associated with increased eNOS mRNA expression. In conclusion, EPO seems to reverse sepsis-induced vasoplegia to NE through the preservation of α1D adrenoceptor mRNA/protein expression, inhibition of GRK2-mediated desensitization, and attenuation of NO overproduction in the mouse aorta. PMID:26025460

  3. 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

  4. Transcatheter aortic valve implantation.

    PubMed

    Kapadia, Samir R; Tuzcu, E Murat

    2009-12-01

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

  5. [Inflammatory abdominal aortic aneurysm].

    PubMed

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

    2000-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2015-08-18

    Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID:26286023

  8. 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

  9. Are Aortic Stent Grafts Safe in Pregnancy?

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-09-01

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

  11. 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

  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. 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

  15. 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 ...

  16. 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

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

    PubMed

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

    2014-01-01

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

  18. 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.

  19. 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

  20. [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

  1. Quadricuspid aortic valves.

    PubMed

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

    2002-12-01

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

  2. Awake transapical aortic valve implantation.

    PubMed

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

    2012-05-01

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

  3. 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

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

    PubMed

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

    2001-01-01

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

  5. 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

  6. 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.

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

    PubMed

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

    2016-01-01

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

  8. Endovascular aortic aneurysm operations.

    PubMed

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

    2002-02-01

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

  9. Aortic wraps a modification to aortic grafting.

    PubMed

    Gordon, J A

    1989-09-01

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

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

    PubMed Central

    Boeldt, DS; Yi, FX; Bird, IM

    2014-01-01

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

  11. Epigenetic regulation of aortic remodeling in hyperhomocysteinemia

    PubMed Central

    Narayanan, Nithya; Pushpakumar, Sathnur Basappa; Givvimani, Srikanth; Kundu, Sourav; Metreveli, Naira; James, Dexter; Bratcher, Adrienne P.; Tyagi, Suresh C.

    2014-01-01

    Hyperhomocysteinemia (HHcy) is prevalent in patients with hypertension and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to the accumulation of collagen in the aorta and resulting in stiffness and development of hypertension. Although the exact mechanism of extracellular matrix (ECM) remodeling is unclear, emerging evidence implicates epigenetic regulation involving DNA methylation. Our purpose was to investigate whether 5-aza-2′-deoxycytidine (Aza), a DNA methyltransferase (DNMT1) inhibitor, reduces high blood pressure (BP) by regulating aortic ECM remodeling in HHcy. Wild-type and cystathionine β-synthase (CBS)+/− HHcy mice were treated with Aza (0.5 mg/kg body weight). In HHcy mice, Aza treatment normalized the plasma homocysteine (Hcy) level and BP. Thoracic and abdominal aorta ultrasound revealed a reduction in the resistive index and wall-to-lumen ratio. Vascular response to phenylephrine, acetylcholine, and sodium nitroprusside improved after Aza in HHcy mice. Histology showed a marked reduction in collagen deposition in the aorta. Aza treatment decreased the expression of DNMT1, MMP9, TIMP1, and S-adenosyl homocysteine hydrolase (SAHH) and upregulated methylene tetrahydrofolate reductase (MTHFR). We conclude that reduction of DNA methylation by Aza in HHcy reduces adverse aortic remodeling to mitigate hypertension.—Narayanan, N., Pushpakumar, S. B., Givvimani, S., Kundu, S., Metreveli, N., James, D., Bratcher, A. P., Tyagi, S. C. Epigenetic regulation of aortic remodeling in hyperhomocysteinemia. PMID:24739303

  12. Lipid Interventions in Aortic Valvular Disease.

    PubMed

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

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

    Hannappel, Ralf; Hauser, Thomas; Friedrich, Rainer

    1995-10-01

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

  14. Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase

    PubMed Central

    TANG, SONG-TAO; SU, HUAN; ZHANG, QIU; TANG, HAI-QIN; WANG, CHANG-JIANG; ZHOU, QING; WEI, WEI; ZHU, HUA-QING; WANG, YUAN

    2016-01-01

    Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP-1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM). In the present study, the rats were randomly divided into the following four groups: i) control; ii) DM; iii) DM + low-dose sitagliptin (10 mg/kg); and iv) DM + high-dose sitagliptin (30 mg/kg). Apart from the control group, all the rats received a high-fat diet for 8 weeks prior to the induction of diabetes with an intraperitoneal injection of streptozotocin. The treatments were then administered for 12 weeks. The serum levels of ET-1, NO, GLP-1 and insulin were measured as well as endothelial function. The expression of ET-1, AMP-activated protein kinase (AMPK) and nuclear factor (NF)-κB/IκBα were determined. After 12 weeks of treatment, the diabetic rats receiving sitagliptin showed significantly elevated serum levels of GLP-1 and NO, and reduced levels of ET-1. Moreover, sitagliptin significantly attenuated endothelial dysfunction as well as the remodeling of the aortic wall. Notably, sitagliptin inhibited ET-1 expression at the transcriptional and translational level in the aorta, which may have been mediated by the suppression of the NF-κB/IκBα system induced by AMPK activation. The majority of the above-mentioned effects were dose dependent. Taken together, the findings of the present study indicate that sitagliptin inhibits ET-1 expression in the aortic endothelium by suppressing the NF-κB/IκBα system through the activation of the AMPK pathway in diabetic rats. These findings further demonstrate some of the vasoprotective properties

  15. Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase.

    PubMed

    Tang, Song-Tao; Su, Huan; Zhang, Qiu; Tang, Hai-Qin; Wang, Chang-Jiang; Zhou, Qing; Wei, Wei; Zhu, Hua-Qing; Wang, Yuan

    2016-06-01

    Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP‑1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM). In the present study, the rats were randomly divided into the following four groups: i) control; ii) DM; iii) DM + low‑dose sitagliptin (10 mg/kg); and iv) DM + high‑dose sitagliptin (30 mg/kg). Apart from the control group, all the rats received a high-fat diet for 8 weeks prior to the induction of diabetes with an intraperitoneal injection of streptozotocin. The treatments were then administered for 12 weeks. The serum levels of ET-1, NO, GLP-1 and insulin were measured as well as endothelial function. The expression of ET-1, AMP-activated protein kinase (AMPK) and nuclear factor (NF)-κB/IκBα were determined. After 12 weeks of treatment, the diabetic rats receiving sitagliptin showed significantly elevated serum levels of GLP-1 and NO, and reduced levels of ET-1. Moreover, sitagliptin significantly attenuated endothelial dysfunction as well as the remodeling of the aortic wall. Notably, sitagliptin inhibited ET-1 expression at the transcriptional and translational level in the aorta, which may have been mediated by the suppression of the NF-κB/IκBα system induced by AMPK activation. The majority of the above-mentioned effects were dose dependent. Taken together, the findings of the present study indicate that sitagliptin inhibits ET-1 expression in the aortic endothelium by suppressing the NF-κB/IκBα system through the activation of the AMPK pathway in diabetic rats. These findings further demonstrate some of the

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

    PubMed

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

    2014-06-01

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

  17. 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}.

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

    PubMed

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

    2011-04-01

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

  19. Genetics, Pregnancy, and Aortic Degeneration.

    PubMed

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

    2016-01-01

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

  20. 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

  1. 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

  2. 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

  3. Overexpression of steroidogenic acute regulatory protein in rat aortic endothelial cells attenuates palmitic acid-induced inflammation and reduction in nitric oxide bioavailability

    PubMed Central

    2012-01-01

    Background Endothelial dysfunction is a well documented evidence for the onset of atherosclerosis and other cardiovascular diseases. Lipids disorder is among the main risk factors for endothelial dysfunction in these diseases. Steroidogenic acute regulatory protein (StAR), one of the cholesterol transporters, plays an important role in the maintenance of intracellular lipid homeostasis. However, the effect of StAR on endothelial dysfunction is not well understood. Palmitic acid (PA) has been shown to decrease eNOS activity and induce inflammation, both are the causes of endothelial dysfunction, in an endothelial cell culture model. Methods StAR gene was introduced into primary rat aortic endothelial cells by adenovirus infection. Real-time PCR and Western blotting were performed to determine the relative genes and proteins expression level to elucidate the underlying mechanism. The free fatty acid and cholesterol quantification kits were used to detect total cellular free fatty acid and cholesterol. The levels of inflammatory factors and nitric oxide were determined by ELISA and classic Griess reagent methods respectively. Results We successfully overexpressed StAR in primary rat aortic endothelial cells. Following StAR overexpression, mRNA levels of IL-1β, TNFα, IL6 and VCAM-1 and protein levels of IL-1β, , TNFα and IL-6 in culture supernatant were significantly decreased, which duing to blocke NFκB nuclear translocation and activation. Moreover, StAR overexpression attenuated the PA-induced reduction of nitric oxide bioavailability by protecting the bioactivity of pAkt/peNOS/NO pathway. Furthermore, the key genes involved in lipid metabolism were greatly reduced following StAR overexpression. In order to investigate the underlying mechanism, cerulenin and lovastatin, the inhibitor of fatty acid and cholesterol synthase, were added prior to PA treatment. The results showed that both cerulenin and lovastatin had a similar effect as StAR overexpression. On the

  4. [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

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

    PubMed Central

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

    2010-01-01

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

  6. Influence of coronary artery diameter on eNOS protein content

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  7. 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.

  8. 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

  9. Almanac 2014: aortic valve disease.

    PubMed

    Otto, Catherine M

    2015-06-01

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

  10. Infrarenal Aortic Occlusion

    PubMed Central

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

    1978-01-01

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

  11. Neuroprotection during aortic surgery.

    PubMed

    Lindsay, Helen; Srinivas, Coimbatore; Djaiani, George

    2016-09-01

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

  12. 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

  13. 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

  14. 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

  15. 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.

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

    PubMed

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

    2015-03-01

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

  17. 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.

  18. New Insights Into Aortic Diseases

    PubMed Central

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

    2013-01-01

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

  19. 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

  20. Non coding RNAs in aortic aneurysmal disease

    PubMed Central

    Duggirala, Aparna; Delogu, Francesca; Angelini, Timothy G.; Smith, Tanya; Caputo, Massimo; Rajakaruna, Cha; Emanueli, Costanza

    2015-01-01

    An aneurysm is a local dilatation of a vessel wall which is >50% its original diameter. Within the spectrum of cardiovascular diseases, aortic aneurysms are among the most challenging to treat. Most patients present acutely after aneurysm rupture or dissection from a previous asymptomatic condition and are managed by open surgical or endovascular repair. In addition, patients may harbor concurrent disease contraindicating surgical intervention. Collectively, these factors have driven the search for alternative methods of identifying, monitoring and treating aortic aneurisms using less invasive approaches. Non-coding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs have opened the field of ncRNAs capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers for aortic aneurysm. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focus at ncRNA roles in aorta aneurysms. We discuss the potential of therapeutic interventions targeting ncRNAs and we describe the research models allowing for mechanistic studies and clinical translation attempts for controlling aneurysm progression. Furthermore, we discuss the potential role of microRNAs and lncRNAs as clinical biomarkers. PMID:25883602

  1. Fluid dynamics of aortic valve stenosis

    NASA Astrophysics Data System (ADS)

    Keshavarz-Motamed, Zahra; Maftoon, Nima

    2009-11-01

    Aortic valve stenosis, which causes considerable constriction of the flow passage, is one of the most frequent cardiovascular diseases and is the most common cause of the valvular replacements which take place for around 100,000 per year in North America. Furthermore, it is considered as the most frequent cardiac disease after arterial hypertension and coronary artery disease. The objective of this study is to develop an analytical model considering the coupling effect between fluid flow and elastic deformation with reasonable boundary conditions to describe the effect of AS on the left ventricle and the aorta. The pulsatile and Newtonian blood flow through aortic stenosis with vascular wall deformability is analyzed and its effects are discussed in terms of flow parameters such as velocity, resistance to flow, shear stress distribution and pressure loss. Meanwhile we developed analytical expressions to improve the comprehension of the transvalvular hemodynamics and the aortic stenosis hemodynamics which is of great interest because of one main reason. To medical scientists, an accurate knowledge of the mechanical properties of whole blood flow in the aorta can suggest a new diagnostic tool.

  2. Molecular Mechanisms of Thoracic Aortic Dissection

    PubMed Central

    Wu, Darrell; Shen, Ying H.; Russell, Ludivine; Coselli, Joseph S.; LeMaire, Scott A.

    2013-01-01

    Thoracic aortic dissection (TAD) is a highly lethal vascular disease. In many patients with TAD, the aorta progressively dilates and ultimately ruptures. Dissection formation, progression, and rupture cannot be reliably prevented pharmacologically because the molecular mechanisms of aortic wall degeneration are poorly understood. The key histopathologic feature of TAD is medial degeneration, a process characterized by smooth muscle cell depletion and extracellular matrix degradation. These structural changes have a profound impact on the functional properties of the aortic wall and can result from excessive protease-mediated destruction of the extracellular matrix, altered signaling pathways, and altered gene expression. Review of the literature reveals differences in the processes that lead to ascending versus descending and sporadic versus hereditary TAD. These differences add to the complexity of this disease. Although tremendous progress has been made in diagnosing and treating TAD, a better understanding of the molecular, cellular, and genetic mechanisms that cause this disease is necessary to developing more effective preventative and therapeutic treatment strategies. PMID:23856125

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

    PubMed

    Yilmaz, E; Mir, S; Berdeli, A

    2009-12-01

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

  4. 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

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

    PubMed

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

    2015-08-01

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

  6. 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

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

    PubMed

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

    2010-02-01

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

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

    PubMed

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

    2016-09-18

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

  9. New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors.

    PubMed

    Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

    2016-01-01

    Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (-786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles -786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2-5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

  10. New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors

    PubMed Central

    Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

    2016-01-01

    Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (−786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles −786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2–5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

  11. The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans.

    PubMed

    Olivi, L; Gu, Y M; Salvi, E; Liu, Y P; Thijs, L; Velayutham, D; Jin, Y; Jacobs, L; D'Avila, F; Petit, T; Barcella, M; Lanzani, C; Kuznetsova, T; Manunta, P; Barlassina, C; Cusi, D; Staessen, J A

    2015-03-01

    We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P=0.0052) for cardiovascular mortality (4 deaths), 2.75 (P=0.0067) for cardiovascular events (7 endpoints) and 3.10 (P=0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P=0.0003), 2.64 (P=0.0091) and 2.89 (P=0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors.

  12. The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans.

    PubMed

    Olivi, L; Gu, Y M; Salvi, E; Liu, Y P; Thijs, L; Velayutham, D; Jin, Y; Jacobs, L; D'Avila, F; Petit, T; Barcella, M; Lanzani, C; Kuznetsova, T; Manunta, P; Barlassina, C; Cusi, D; Staessen, J A

    2015-03-01

    We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P=0.0052) for cardiovascular mortality (4 deaths), 2.75 (P=0.0067) for cardiovascular events (7 endpoints) and 3.10 (P=0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P=0.0003), 2.64 (P=0.0091) and 2.89 (P=0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors. PMID:25102225

  13. 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

  14. 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

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

    PubMed Central

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

    2014-01-01

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

  16. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve

    PubMed Central

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

  17. Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve.

    PubMed

    Wang, Jun; Wang, Ying; Gu, Weidong; Ni, Buqing; Sun, Haoliang; Yu, Tong; Gu, Wanjun; Chen, Liang; Shao, Yongfeng

    2016-01-01

    RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve. PMID:27493474

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

    PubMed Central

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

    2012-01-01

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

  19. Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms

    PubMed Central

    Wågsäter, Dick; Vorkapic, Emina; van Stijn, Caroline M. W.; Kim, Jason; Lusis, Aldons J.; Eriksson, Per; Tangirala, Rajendra K.

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR−/−) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA. PMID:27659201

  20. 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...

  1. 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...

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

    PubMed

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

    2011-06-01

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

  3. Does atorvastatin induce aortic smooth muscle cell apoptosis in vivo?

    PubMed

    Doyon, Marielle; Hale, Taben Mary; Huot-Marchand, Julie-Emilie; Wu, Rong; de Champlain, Jacques; DeBlois, Denis

    2011-01-01

    It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive rat (SHR) as a well-known reference model of SMC apoptosis induction in vivo by cardiovascular drugs including the calcium channel blocker amlodipine. Atorvastatin was administered to SHR for 3 or 6 weeks either alone or together with amlodipine, a drug combination clinically available to patients. Primary endpoints included aortic medial hypertrophy and aortic SMC hyperplasia, internucleosomal DNA fragmentation and expression of the apoptosis regulatory proteins Bax and Bcl-2. The SHR aorta showed no evidence of SMC apoptosis induction by atorvastatin, even at the high dose of 50 mg kg(-1) day(-1), although the statin significantly reduced oxidative stress after 3 weeks and blood pressure after 6 weeks of administration. Amlodipine-induced regression of aortic hypertophy and aortic SMC hyperplasia were dose- and time-dependent, but there was no interaction between atorvastatin and amlodipine in modulating the primary endpoints. These results do not support the notion that atorvastatin induces SMC apoptosis in the aortic media in vivo.

  4. Evaluation of regional aortic distensibility using color kinesis.

    PubMed

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

    2003-01-01

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

  5. 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

  6. [ENDOVASCULAR ABDOMINAL AORTIC ANEURISM REPAIR].

    PubMed

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

    2015-01-01

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

  7. 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

  8. Resveratrol Inhibits Aortic Root Dilatation in the Fbn1C1039G/+ Marfan Mouse Model

    PubMed Central

    Hibender, Stijntje; Franken, Romy; van Roomen, Cindy; ter Braake, Anique; van der Made, Ingeborg; Schermer, Edith E.; Gunst, Quinn; van den Hoff, Maurice J.; Lutgens, Esther; Pinto, Yigal M.; Groenink, Maarten; Zwinderman, Aeilko H.; Mulder, Barbara J.M.; de Vries, Carlie J.M.

    2016-01-01

    Objective— Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene. Patients with MFS are at risk of aortic aneurysm formation and dissection. Usually, blood pressure–lowering drugs are used to reduce aortic events; however, this is not sufficient for most patients. In the aorta of smooth muscle cell–specific sirtuin-1–deficient mice, spontaneous aneurysm formation and senescence are observed. Resveratrol is known to enhance sirtuin-1 activity and to reduce senescence, which prompted us to investigate the effectiveness of resveratrol in inhibition of aortic dilatation in the Fbn1C1039G/+ MFS mouse model. Approach and Results— Aortic senescence strongly correlates with aortic root dilatation rate in MFS mice. However, although resveratrol inhibits aortic dilatation, it only shows a trend toward reduced aortic senescence. Resveratrol enhances nuclear localization of sirtuin-1 in the vessel wall and, in contrast to losartan, does not affect leukocyte infiltration nor activation of SMAD2 and extracellular signal–regulated kinases 1/2 (ERK1/2). Interestingly, specific sirtuin-1 activation (SRT1720) or inhibition (sirtinol) in MFS mice does not affect aortic root dilatation rate, although senescence is changed. Resveratrol reduces aortic elastin breaks and decreases micro-RNA-29b expression coinciding with enhanced antiapoptotic Bcl-2 expression and decreased number of terminal apoptotic cells. In cultured smooth muscle cells, the resveratrol effect on micro-RNA-29b downregulation is endothelial cell and nuclear factor κB-dependent. Conclusions— Resveratrol inhibits aortic root dilatation in MFS mice by promoting elastin integrity and smooth muscle cell survival, involving downregulation of the aneurysm-related micro-RNA-29b in the aorta. On the basis of these data, resveratrol holds promise as a novel intervention strategy for patients with MFS. PMID:27283746

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-01-01

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

  11. Transcriptional regulation of two stage-specifically expressed genes in the protozoan parasite Toxoplasma gondii

    PubMed Central

    Kibe, Michael K.; Coppin, Alexandra; Dendouga, Najoua; Oria, Gabrielle; Meurice, Edwige; Mortuaire, Marlène; Madec, Edwige; Tomavo, Stanislas

    2005-01-01

    The protozoan parasite Toxoplasma gondii differentially expresses two distinct enolase isoenzymes known as ENO1 and ENO2, respectively. To understand differential gene expression during tachyzoite to bradyzoite conversion, we have characterized the two T.gondii enolase promoters. No homology could be found between these sequences and no TATA or CCAAT boxes were evident. The differential activation of the ENO1 and ENO2 promoters during tachyzoite to bradyzoite differentiation was investigated by deletion analysis of 5′-flanking regions fused to the chloramphenicol acetyltransferase reporter followed by transient transfection. Our data indicate that in proliferating tachyzoites, the repression of ENO1 involves a negative distal regulatory region (nucleotides −1245 to −625) in the promoter whereas a proximal regulatory region in the ENO2 promoter directs expression at a low level. In contrast, the promoter activity of ENO1 is highly induced following the conversion of tachyzoites into resting bradyzoites. The ENO2 promoter analysis in bradyzoites showed that there are two upstream repression sites (nucleotides −1929 to −1067 and −456 to −222). Furthermore, electrophoresis mobility shift assays demonstrated the presence of DNA-binding proteins in tachyzoite and bradyzoite nuclear lysates that bound to stress response elements (STRE), heat shock-like elements (HSE) and other cis-regulatory elements in the upstream regulatory regions of ENO1 and ENO2. Mutation of the consensus AGGGG sequence, completely abolished protein binding to an oligonucleotide containing this element. This study defines the first characterization of cis-regulatory elements and putative transcription factors involved in gene regulation of the important pathogen T.gondii. PMID:15784612

  12. [New aspects in aortic valve disease].

    PubMed

    Tornos, P

    2001-01-01

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

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

    PubMed

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

    2014-03-15

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

  14. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice

    PubMed Central

    Miller, Jordan D.; Weiss, Robert M.; Serrano, Kristine M.; Brooks, Robert M.; Berry, Christopher J.; Zimmerman, Kathy; Young, Stephen G.; Heistad, Donald D.

    2009-01-01

    Background Treatment of hyperlipidemia produces functional and structural improvements in atherosclerotic vessels. However, the effects of treating hyperlipidemia on the structure and function of the aortic valve has been controversial, and any effects could be confounded by pleiotropic effects of hypolipidemic treatment. The goal of this study was to determine whether reducing elevated plasma lipid levels with a “genetic switch” in Reversa mice (Ldlr−/−/Apob100/100/Mttpfl/fl/Mx1Cre+/+) reduces oxidative stress, reduces proosteogenic signaling, and retards the progression of aortic valve disease. Methods and Results After 6 months of hypercholesterolemia, Reversa mice exhibited increases in superoxide, lipid deposition, myofibroblast activation, calcium deposition, and pro-osteogenic protein expression in the aortic valve. Maximum aortic valve cusp separation, as judged by echocardiography, was not altered. During an additional 6 months of hypercholesterolemia, superoxide levels, valvular lipid deposition, and myofibroblast activation remained elevated. Furthermore, calcium deposition and pro-osteogenic gene expression became more pronounced and the aortic cusp separation decreased from 0.85 ± 0.04 to 0.70 ± 0.04 mm (mean ± SE; p < 0.05). Rapid normalization of cholesterol levels at 6 months of age (by inducing expression of Cre recombinase) normalized aortic valve superoxide levels, decreased myofibroblast activation, reduced valvular calcium burden, suppressed pro-osteogenic signaling cascades, and prevented the reductions in aortic valve cusp separation. Conclusions Collectively, these data indicate that reducing plasma lipid levels by genetic inactivation of the mttp gene in hypercholesterolemic mice with early aortic valve disease normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of aortic valve stenosis. PMID:19433756

  15. 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.

  16. Aortic valve orifice equation independent of valvular flow intervals: application to aortic valve area computation in aortic stenosis and comparison with the Gorlin formula.

    PubMed

    Seitz, W; Oppenheimer, L; McIlroy, M; Nelson, D; Operschall, J

    1986-12-01

    An orifice equation is derived relating the effective aortic valve area, A, the average aortic valve pressure gradient, dP, the stroke volume, SV, and the heart frequency, FH, through considerations of momentum conservation across the aortic valve. This leads to a formula consistent with Newton's second law of motion. The form of the new equation is A = (7.5 X 10(-5)) SV FH2/Pd, where A, VS, FH and Pd are expressed in cm2, ml, s-1 and mmHg, respectively. Aortic valve areas computed with the new orifice equation are found to correlate with those computed by the Gorlin formula in conditions of resting haemodynamic states at a level of r = 0.86, SE = 0.25 cm2, N = 120. The results suggest that the new formula may be considered as an independent orifice equation having a similar domain of validity as the Gorlin formula. The new equation offers the possibility of deriving additional useful haemodynamic relationships through combination with established cardiological formulas and applying it in a noninvasive Doppler ultrasonic or echocardiographic context.

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

    PubMed Central

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

    2014-01-01

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

  18. 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

  19. 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

  20. 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

  1. Abdominal aortic feminism.

    PubMed

    Mortimer, Alice Emily

    2014-11-14

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

  2. Genes and Abdominal Aortic Aneurysm

    PubMed Central

    Hinterseher, Irene; Tromp, Gerard; Kuivaniemi, Helena

    2010-01-01

    Abdominal aortic aneurysm (AAA) is a multifactorial disease with a strong genetic component. Since first candidate gene studies were published 20 years ago, nearly 100 genetic association studies using single nucleotide polymorphisms (SNPs) in biologically relevant genes have been reported on AAA. The studies investigated SNPs in genes of the extracellular matrix, the cardiovascular system, the immune system, and signaling pathways. Very few studies were large enough to draw firm conclusions and very few results could be replicated in another sample set. The more recent unbiased approaches are family-based DNA linkage studies and genome-wide genetic association studies, which have the potential of identifying the genetic basis for AAA, if appropriately powered and well-characterized large AAA cohorts are used. SNPs associated with AAA have already been identified in these large multicenter studies. One significant association was of a variant in a gene called CNTN3 which is located on chromosome 3p12.3. Two follow-up studies, however, could not replicate the association. Two other SNPs, which are located on chromosome 9p21 and 9q33 were replicated in other samples. The two genes with the strongest supporting evidence of contribution to the genetic risk for AAA are the CDKN2BAS gene, also known as ANRIL, which encodes an antisense RNA that regulates expression of the cyclin-dependent kinase inhibitors CDKN2A and CDKN2B, and DAB2IP, which encodes an inhibitor of cell growth and survival. Functional studies are now needed to establish the mechanisms by which these genes contribute to AAA pathogenesis. PMID:21146954

  3. Open aortic surgery after thoracic endovascular aortic repair.

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2015-04-01

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

  5. 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

  6. 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.

  7. 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.

  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.

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2009-08-04

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

  12. 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.

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

    PubMed

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

    2005-12-01

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

  14. 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

  15. Abdominal aortic aneurysms: case report

    PubMed Central

    Hadida, Camille; Rajwani, Moez

    1998-01-01

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

  16. Aortic and other arterial injuries.

    PubMed Central

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

    1975-01-01

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

  17. Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity

    PubMed Central

    Atkins, Samantha K; Moore, Alison N; Sucosky, Philippe

    2016-01-01

    AIM: To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects. METHODS: Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography. RESULTS: Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively). CONCLUSION: The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA. PMID:26839660

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

    PubMed

    Ryugo, Masahiro; Takasaki, Taiichi

    2016-02-01

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

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

    PubMed

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

    2015-01-01

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

  20. Alternative splicing impairs soluble guanylyl cyclase function in aortic aneurysm.

    PubMed

    Martin, Emil; Golunski, Eva; Laing, Susan T; Estrera, Anthony L; Sharina, Iraida G

    2014-12-01

    Nitric oxide (NO) receptor soluble guanylyl cyclase (sGC) is a key regulator of several important vascular functions and is important for maintaining cardiovascular homeostasis and vascular plasticity. Diminished sGC expression and function contributes to pathogenesis of several cardiovascular diseases. However, the processes that control sGC expression in vascular tissue remain poorly understood. Previous work in animal and cell models revealed the complexity of alternative splicing of sGC genes and demonstrated its importance in modulation of sGC function. The aim of this study was to examine the role of alternative splicing of α1 and β1 sGC in healthy and diseased human vascular tissue. Our study found a variety of α1 and β1 sGC splice forms expressed in human aorta. Their composition and abundance were different between samples of aortic tissue removed during surgical repair of aortic aneurysm and samples of aortas without aneurysm. Aortas with aneurysm demonstrated decreased sGC activity, which correlated with increased expression of dysfunctional sGC splice variants. In addition, the expression of 55-kDa oxidation-resistant α1 isoform B sGC (α1-IsoB) was significantly lower in aortic samples with aneurysm. The α1-IsoB splice variant was demonstrated to support sGC activity in aortic lysates. Together, our results suggest that alternative splicing contributes to diminished sGC function in vascular dysfunction. Precise understanding of sGC splicing regulation could help to design new therapeutic interventions and to personalize sGC-targeting therapies in treatments of vascular disease.

  1. 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

  2. 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

  3. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions.

    PubMed

    Ghosh, Suparna; Lakshmanan, Arun P; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R; Ding, Hong

    2015-12-01

    The cellular mechanisms whereby metformin, the first line drug for type 2 diabetes (T2DM), mediates its antidiabetic effects remain elusive, particularly as to whether metformin has a direct protective action on the vasculature. This study was designed to determine if a brief 3-h exposure to metformin protects endothelial function against the effects of hyperglycaemia. We investigated the protective effects of metformin on endothelial-dependent vasodilatation (EDV) in thoracic aortae from T2DM db/db mice and on high glucose (HG, 40 mM) induced changes in endothelial nitric oxide synthase (eNOS) signaling in mouse microvascular endothelial cells (MMECs) in culture. Exposure of aortae from db+/? non-diabetic control mice to high glucose (HG, 40 mM) containing Krebs for 3-h significantly (P<0.05) reduced acetylcholine (ACh)-induced EDV compared to ACh-induced EDV in aortae maintained in normal glucose (NG, 11 mM) Krebs. The reduction of EDV was partially reversed following a 3-h exposure to 50 μM metformin; metformin also improved ACh-induced EDV in aortae from diabetic db/db mice. Immunoblot analysis of MMECs cultured in HG versus NG revealed a significant reduction of the ratio of phosphorylated (p-eNOS)/eNOS and p-Akt/Akt, but not the expression of total eNOS or Akt. The 3-h exposure of MMECs to metformin significantly (P<0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1. Our data indicate that a 3-h exposure to metformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt.

  4. Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177

    PubMed Central

    Carneiro, Fernando S.; Giachini, Fernanda R.C.; Carneiro, Zidonia N.; Lima, Victor V.; Ergul, Adviye; Webb, R. Clinton; Tostes, Rita C.

    2011-01-01

    Introduction Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90–95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED. Aim Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability. Methods Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured. Main Outcome Measure GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein. Results GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages. Conclusion Although GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve

    PubMed Central

    Rueda-Martínez, Carmen; Fernández, M. Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

    2016-01-01

    Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180–240 days old) and 56 old (300–440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta. PMID:27711171

  9. 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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2014-09-23

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

  13. Chronic Type A Aortic Dissection

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  15. 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

  16. Functional role of NF-κB in expression of human endothelial nitric oxide synthase.

    PubMed

    Lee, Kyu-Sun; Kim, Joohwan; Kwak, Su-Nam; Lee, Kwang-Soon; Lee, Dong-Keon; Ha, Kwon-Soo; Won, Moo-Ho; Jeoung, Dooil; Lee, Hansoo; Kwon, Young-Guen; Kim, Young-Myeong

    2014-05-23

    The transcription factor NF-κB has an essential role in inflammation in endothelial cells. Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) prevents vascular inflammation. However, the molecular mechanism underlying NF-κB-mediated regulation of eNOS expression has not been clearly elucidated. We here found that NF-κB-activating stimuli, such as lipopolysaccharide, tumor necrosis factor-α (TNF-α), and interleukin-1β, suppressed eNOS mRNA and protein levels by decreasing mRNA stability, without affecting promoter activity. TNF-α-mediated suppression of eNOS expression, mRNA stability, and 3'-untranslated region (3'UTR) activity were inhibited by NF-κB inhibitors and Dicer knockdown, but not by p38 MAPK and MEK inhibitors, suggesting the involvement of NF-κB-responsive miRNAs in eNOS expression. Moreover, TNF-α increased MIR155HG expression and promoter activity as well as miR-155 biogenesis, and these increases were blocked by NF-κB inhibitors. Transfection with antagomiR-155 blocked TNF-α-mediated suppression of eNOS 3'UTR activity, eNOS mRNA and protein levels, and NO and cGMP production. These data provide evidence that NF-κB is a negative regulator of eNOS expression via upregulation of miR-155 under inflammatory conditions. These results suggest that NF-κB is a potential therapeutic target for preventing vascular inflammation and endothelial dysfunction induced by suppression of miR-155-mediated eNOS expression. PMID:24769202

  17. Functional role of NF-κB in expression of human endothelial nitric oxide synthase.

    PubMed

    Lee, Kyu-Sun; Kim, Joohwan; Kwak, Su-Nam; Lee, Kwang-Soon; Lee, Dong-Keon; Ha, Kwon-Soo; Won, Moo-Ho; Jeoung, Dooil; Lee, Hansoo; Kwon, Young-Guen; Kim, Young-Myeong

    2014-05-23

    The transcription factor NF-κB has an essential role in inflammation in endothelial cells. Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) prevents vascular inflammation. However, the molecular mechanism underlying NF-κB-mediated regulation of eNOS expression has not been clearly elucidated. We here found that NF-κB-activating stimuli, such as lipopolysaccharide, tumor necrosis factor-α (TNF-α), and interleukin-1β, suppressed eNOS mRNA and protein levels by decreasing mRNA stability, without affecting promoter activity. TNF-α-mediated suppression of eNOS expression, mRNA stability, and 3'-untranslated region (3'UTR) activity were inhibited by NF-κB inhibitors and Dicer knockdown, but not by p38 MAPK and MEK inhibitors, suggesting the involvement of NF-κB-responsive miRNAs in eNOS expression. Moreover, TNF-α increased MIR155HG expression and promoter activity as well as miR-155 biogenesis, and these increases were blocked by NF-κB inhibitors. Transfection with antagomiR-155 blocked TNF-α-mediated suppression of eNOS 3'UTR activity, eNOS mRNA and protein levels, and NO and cGMP production. These data provide evidence that NF-κB is a negative regulator of eNOS expression via upregulation of miR-155 under inflammatory conditions. These results suggest that NF-κB is a potential therapeutic target for preventing vascular inflammation and endothelial dysfunction induced by suppression of miR-155-mediated eNOS expression.

  18. 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

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

    PubMed

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

    2016-01-01

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

  20. Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice.

    PubMed

    Roos, Carolyn M; Hagler, Michael; Zhang, Bin; Oehler, Elise A; Arghami, Arman; Miller, Jordan D

    2013-11-15

    The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD(+/+)) and manganese SOD heterozygous haploinsufficient (MnSOD(+/-)) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16(ink4a), a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD(+/+) and MnSOD(+/-) mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD(+/+) and MnSOD(+/-) mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD(+/+) mice but significantly impaired endothelial function in MnSOD(+/-) mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific. PMID:23997094

  1. 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

  2. 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

  3. Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome.

    PubMed

    Seckin, Yuksel; Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Cagin, Yasir Furkan; Gozukara, Harika; Bılgıc, Yılmaz; Yildirim, Oguzhan; Turkoz, Yusuf; Aksungur, Zeynep

    2016-01-01

    Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS. PMID:27594880

  4. 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.

  5. 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.

  6. 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

  7. Spring retractor: a new adjunct for aortic valve surgery.

    PubMed

    Izzat, Mohammad Bashar

    2011-07-01

    We describe a new aortic retractor that is effective in maintaining aortic root geometry and providing for adequate intraoperative visual valve assessment, and therefore enables the surgeon to perform precise aortic valve repair or replacement procedures.

  8. An Investigation of the Relationship between the eNOS Gene Polymorphism and Diagnosed Migraine.

    PubMed

    Güler, S; Gürkan, H; Tozkir, H; Turan, N; Çelik, Y

    2014-12-01

    We investigated the phenotype-genotype association of the following endothelial nitric oxide synthase (eNOS) gene polymorphisms, rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851, in patients suffering from migraine living in Edirne, Turkey. A total of 175 individuals, who had been diagnosed with migraine between April 2013 and December 2013, at the Neurology Department, Trakya University Medical Faculty, Edirne, Turkey, and 125 healthy controls were recruited. The above gene polymorphisms were analyzed from genomic DNA in both patient and control groups, using the pyro-sequencing method. The eNOS rs1799983 TT genotype frequency in migraine patients who had a headache duration of longer than 24 hours was statistically significantly higher than in patients who had migraine attacks that lasted under 24 hours (p = 0.047). In terms of the AGGTGGA haplotype, the severity of headache was statistically significant, and was found to be severe in 61.0% (p = 0.0001). Also in terms of the AGGTGGA haplotype, the duration of headache was statistically significant, and was >24 hours in 56.0% of patients (p = 0.008). In our study, there was no significant genotypephenotype relationship between eNOS rs743506, rs2070744, rs1799983, rs180079, rs3918226, rs207468799 and rs148554851 gene polymorphisms and migraine patients with and without aura living in Edirne, Turkey. The AGGTGGA haplotype constitutes a risk in terms of the severity and the duration of headaches in patients with migraine. This risk is significantly higher in patients with migraine with aura than patients with migraine without aura.

  9. Type B Aortic Dissection Repair Using a Thoraflex Hybrid Prosthesis in a Complex Aortic Arch Anatomy

    PubMed Central

    Ghanem, Moussa Abi; Gomez-Sanchez, Mario; Chaufour, Xavier; Marcheix, Bertrand

    2016-01-01

    Thoracic endovascular aortic repair (TEVAR) is recognized as an attractive option to treat complicated Type B aortic dissection. Nevertheless, TEVAR is not always technically possible. We report the case of a 53-year-old male with complicated Type B aortic dissection, in the setting of a complex anomalous aortic arch anatomy with an aneurysmal aberrant right subclavian artery. He was successfully treated by the frozen elephant trunk technique using the Thoraflex hybrid graft.

  10. Severe Aortic Stenosis Associated with Unicommissural Unicuspid Aortic Valve in a Middle Aged Male

    PubMed Central

    Kwon, Hee-Jin; Kim, Song Soo; Sun, Byung Joo; Jin, Sun Ah; Kim, Jun-Hyung; Lee, Jae-Hwan; Choi, Siwan; Jeong, Jin-Ok; Seong, In-Whan

    2016-01-01

    Unicuspid aortic valve (UAV) is an extremely rare form of congenital aortic valvular abnormality. Although UAV shows similar clinical characteristics to bicuspid aortic valve, the clinical symptoms develop at earlier age and progress at a faster pace in UAV. In this report, we are presenting a 42-year-old male with severe aortic stenosis associated with unicommissural UAV. The patients underwent a successful Bentall operation. PMID:27721957

  11. Aromatase Is Required for Female Abdominal Aortic Aneurysm Protection

    PubMed Central

    Johnston, William F.; Salmon, Morgan; Su, Gang; Lu, Guanyi; Ailawadi, Gorav; Upchurch, Gilbert R.

    2014-01-01

    IL-1β and were associated with increased macrophage staining and decreased elastin staining. Regarding serum hormone levels, decreasing estradiol levels correlated with increasing aortic diameter (R=−0.565, p<0.01). By confocal immunohistochemistry, both human and mouse AAA smooth muscle cells (smooth muscle α actin positive) and macrophages (CD68 positive or Mac-2 positive) expressed aromatase. Conclusions The protective effect of female gender on AAAs is due to estrogen synthesis and requires the presence of both ovarian and extragonadal/peripheral aromatase. Peripheral estrogen synthesis accounts for roughly half of the protective effect of female gender. If peripheral aromatase could be targeted, high levels of local estrogen could be produced and may avoid the side effects of systemic estrogen. PMID:24582702

  12. Isolation and expression of enolase gene in Fusarium oxysporum f. sp. lycopersici.

    PubMed

    Macías-Sánchez, Karla Lizbeth; García-Soto, Jesús; Roncero, M Isabel G; Hernández-Monjaraz, Wendy; Caudillo-Pérez, César; Martínez-Cadena, Ma Guadalupe

    2015-01-01

    Fusarium oxysporum f. sp. lycopersici is a fungus responsible for the tomato disease known as fusariosis. Enolase, which is the enzyme that catalyzes the reaction of 2-phosphoglycerate to phosphoenolpyruvate, is present during glycolysis. Enolase genes have been isolated from bacteria and fungi, among other organisms. In this research, a large portion of the enolase, eno, gene sequence was isolated from F. oxysporum and compared with those of other microorganisms, revealing a similarity of 51-69 %. We analyzed the copy number of the eno gene and determined that only a single copy is present in F. oxysporum, as in several fungi, such as Candida albicans and Aspergillus oryzae. We also detected the expression of the eno gene by reverse transcription-polymerase chain reaction during in vitro growth under two growth conditions where glucose was used as the carbon source, and we observed the same eno gene expression levels under both growth conditions.

  13. Transcatheter aortic valve implantation in Jehovah's Witness patients with symptomatic severe aortic valve stenosis

    PubMed Central

    Buz, Semih; Pasic, Miralem; Unbehaun, Axel; Hetzer, Roland

    2012-01-01

    Transcatheter aortic valve implantation (TAVI) is currently reserved for high or prohibitive surgical-risk patients with aortic valve stenosis. We report on successful TAVI in two Jehovah's witness patients. It offers a simple and effective treatment of severe aortic valve stenosis in high-risk patients who refuse the use of allogeneic blood and blood products. PMID:22753437

  14. Contemporary management of aortic stenosis: surgical aortic valve replacement remains the gold standard.

    PubMed

    Walther, Thomas; Blumenstein, Johannes; van Linden, Arnaud; Kempfert, Jörg

    2012-11-01

    Aortic valve disease is the most frequent acquired heart valve lesion in humans. In western communities, approximately 90% of patients present with aortic stenosis (AS), predominantly of a calcific degenerative aetiology. The remaining approximately 10% of patients predominantly present with aortic valve incompetence.

  15. Cervical aortic arch and a new type of double aortic arch. Report of a case.

    PubMed Central

    Cornali, M; Reginato, E; Azzolina, G

    1976-01-01

    A case of cervical aortic arch is reported. To the best of our knowledge, it is the first to be associated with a serious intracardiac anomaly. In addition, it is part of a new type of double aortic arch, caused by failure of reabsorption of both dorsal aortic roots and persistence of the fourth right and second (or third) left branchial arches. PMID:971387

  16. Aortic Valve Surgery: Minimally Invasive Options

    PubMed Central

    Ramlawi, Basel; Bedeir, Kareem; Lamelas, Joseph

    2016-01-01

    Minimally invasive aortic valve surgery has not been adopted by a significant proportion of cardiac surgeons despite proven benefits. This may be related to a high learning curve and technical issues requiring retraining. In this review, we discuss the data for minimally invasive aortic valve surgery and describe our operative technique for both ministernotomy and anterior thoracotomy approaches. We also discuss the advent of novel sutureless valves and how these techniques compare to available transcatheter aortic valve procedures. PMID:27127559

  17. 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

  18. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study

    PubMed Central

    Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Corte, Cristina della; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena

    2016-01-01

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

  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.

  20. MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

    SciTech Connect

    Bi, Rui; Bao, Chunrong; Jiang, Lianyong; Liu, Hao; Yang, Yang; Mei, Ju; Ding, Fangbao

    2015-05-01

    Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.

  1. Aortic root dilatation in young men with normally functioning bicuspid aortic valves

    PubMed Central

    Nistri, S; Sorbo, M; Marin, M; Palisi, M; Scognamiglio, R; Thiene, G

    1999-01-01

    OBJECTIVE—To evaluate the dimensions of the aortic root in a selected population of young males with isolated normally functioning bicuspid aortic valve.
DESIGN AND SETTING—Echocardiographic and Doppler evaluation of conscripts with bicuspid aortic valve at the time of military pre-enrolment screening in two military hospitals.
SUBJECTS AND METHODS—66 consecutive young men with a normally functioning bicuspid aortic valve were studied to assess aortic size at four aortic levels: annulus, sinuses of Valsalva, supra-aortic ridge, and proximal ascending aorta; 70 consecutive normal young subjects, matched for age and body surface area, were used as controls.
RESULTS—In men with a bicuspid aortic valve, the diameter of the aortic root was significantly larger than in controls at the sinuses (3.16 (0.37) v 2.87 (0.31) cm, p < 0.001), at the supra-aortic ridge (2.64 (0.46) v 2.47 (0.28) cm, p = 0.01), and at the level of the proximal ascending aorta (3.12 (0.48) v 2.69 (0.28) cm, p < 0.001). The prevalence of aortic root dilatation was 7.5% at the annulus (5/66), 19.6% at the sinuses (13/66), 15% at the supra-aortic ridge (10/66), and 43.9% at the ascending aorta (29/66); 32 subjects (48%) had aortic root dimensions comparable with controls, while 34 (52%) had definitely abnormal aortic root dimensions.
CONCLUSIONS—Aortic root enlargement in people with a bicuspid aortic valve occurs independently of haemodynamic abnormalities, age, and body size. However, there appear to be different subgroups of young adults with bicuspid aortic valves, one of which is characterised by aortic dilatation, possibly caused by a congenital abnormality of the aortic wall.


Keywords: bicuspid aortic valve; aortic root dilatation PMID:10377302

  2. Hybrid treatment of penetrating aortic ulcer.

    PubMed

    Lara, Juan Antonio Herrero; Martins-Romêo, Daniela de Araújo; Escudero, Carlos Caparrós; Vázquez, Rosa María Lepe; Falcón, María Del Carmen Prieto; Batista, Vinicius Bianchi

    2015-01-01

    Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

  3. eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1–Induced Pre-Eclampsia–Like Phenotype

    PubMed Central

    Li, Feng; Hagaman, John R.; Kim, Hyung-Suk; Maeda, Nobuyo; Jennette, J. Charles; Faber, James E.; Karumanchi, S. Ananth; Smithies, Oliver

    2012-01-01

    Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia–like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia–like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467±74 versus 174±23 μg/d), lower creatinine clearance (126±29 versus 452±63 μl/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ETA receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ETA receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia–like phenotype through activation of the endothelin system. PMID:22282588

  4. 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

  5. Low-gradient aortic stenosis.

    PubMed

    Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

    2016-09-01

    An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS.

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

    PubMed Central

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

    2012-01-01

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

  7. Myeloid Mineralocorticoid Receptor Deficiency Inhibits Aortic Constriction-Induced Cardiac Hypertrophy in Mice

    PubMed Central

    Zheng, Xiao Jun; Zhang, Wu Chang; Sun, Xue Nan; Yang, Qing Zhen; Ma, Shu Min; Huang, Baozhuan; Berger, Stefan; Wang, Wang; Wu, Yong; Yu, Ying; Duan, Sheng Zhong; Mortensen, Richard M.

    2014-01-01

    Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims to determine whether MR deficiency in myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid MR knockout (MMRKO) mice and littermate control mice were subjected to abdominal aortic constriction (AAC) or sham operation. We found that AAC-induced cardiac hypertrophy and fibrosis were significantly attenuated in MMRKO mice. Expression of genes important in generating reactive oxygen species was decreased in MMRKO mice, while that of manganese superoxide dismutase increased. Furthermore, expression of genes important in cardiac metabolism was increased in MMRKO hearts. Macrophage infiltration in the heart was inhibited and expression of inflammatory genes was decreased in MMRKO mice. In addition, aortic fibrosis and inflammation were attenuated in MMRKO mice. Taken together, our data indicated that MR deficiency in myeloid cells effectively attenuated aortic constriction-induced cardiac hypertrophy and fibrosis, as well as aortic fibrosis and inflammation. PMID:25354087

  8. Aortic root disease in athletes: aortic root dilation, anomalous coronary artery, bicuspid aortic valve, and Marfan's syndrome.

    PubMed

    Yim, Eugene Sun

    2013-08-01

    Two professional athletes in the U.S. National Basketball Association required surgery for aortic root dilation in 2012. These cases have attracted attention in sports medicine to the importance of aortic root disease in athletes. In addition to aortic root dilation, other forms of aortic disease include anomalous coronary artery, bicuspid aortic valve, and Marfan's syndrome. In this review, electronic database literature searches were performed using the terms "aortic root" and "athletes." The literature search produced 122 manuscripts. Of these, 22 were on aortic root dilation, 21 on anomalous coronary arteries, 12 on bicuspid aortic valves, and 8 on Marfan's syndrome. Aortic root dilation is a condition involving pathologic dilation of the aortic root, which can lead to life-threatening sequelae. Prevalence of the condition among athletes and higher risk athletes in particular sports needs to be better delineated. Normative parameters for aortic root diameter in the general population are proportionate to anthropomorphic variables, but this has not been validated for athletes at the extremes of anthropomorphic indices. Although echocardiography is the favored screening modality, computed tomography (CT) and cardiac magnetic resonance imaging (MRI) are also used for diagnosis and surgical planning. Medical management has utilized beta-blockers, with more recent use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and statins. Indications for surgery are based on comorbidities, degree of dilation, and rate of progression. Management decisions for aortic root dilation in athletes are nuanced and will benefit from the development of evidence-based guidelines. Anomalous coronary artery is another form of aortic disease with relevance in athletes. Diagnosis has traditionally been through cardiac catheterization, but more recently has included evaluation with echocardiography, multislice CT, and MRI. Athletes with this

  9. 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.

  10. 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.

  11. eNOS tag SNP haplotypes in hypertensive disorders of pregnancy.

    PubMed

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

    2012-12-01

    Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n=122), GH (n=138), and PE (n=157). The haplotype formed by "C b G G C" was more frequent in HP compared to GH and PE (p=0.0071), which is supported by previous findings that demonstrated the association of the combination "C b G" with a higher level of nitrite (NO marker). Our results suggest a protective effect of the haplotype "C b G G C" against the development of hypertensive disorders of pregnancy. PMID:23062210

  12. 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.

  13. The role of transesophageal echocardiography in aortic surgery.

    PubMed

    Nowak-Machen, Martina

    2016-09-01

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

  14. [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)

  15. Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

    PubMed Central

    Cooper, Leroy L.; Mitchell, Gary F.

    2016-01-01

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

  16. Congenital quadricuspid aortic valve associated with aortic insufficiency and mitral regurgitation

    PubMed Central

    2013-01-01

    Congenital quadricuspid aortic valve is a rare cardiac anomaly. More than half of the patients with this abnormality will develop aortic insufficiency in adulthood. It is vital that patients with quadricuspid aortic valve who present with progressive aortic regurgitation undergo valve replacement or repair at appropriate time. Here, we present two cases of quadricuspid aortic valve. We first describe a 58-year-old man who had mitral regurgitation and ascending aorta dilatation with quadricuspid aortic valve. He underwent aortic valve replacement and mitral valve plasty and recovered well. The second patient is a 20-year-old asymptomatic boy who has been closely followed up and has not received any surgical treatment. PMID:23587156

  17. Congenital quadricuspid aortic valve associated with aortic insufficiency and mitral regurgitation.

    PubMed

    Zhu, Jiaquan; Zhang, Junwen; Wu, Shubin; Zhang, Yunjiao; Ding, Fangbao; Mei, Ju

    2013-01-01

    Congenital quadricuspid aortic valve is a rare cardiac anomaly. More than half of the patients with this abnormality will develop aortic insufficiency in adulthood. It is vital that patients with quadricuspid aortic valve who present with progressive aortic regurgitation undergo valve replacement or repair at appropriate time. Here, we present two cases of quadricuspid aortic valve. We first describe a 58-year-old man who had mitral regurgitation and ascending aorta dilatation with quadricuspid aortic valve. He underwent aortic valve replacement and mitral valve plasty and recovered well. The second patient is a 20-year-old asymptomatic boy who has been closely followed up and has not received any surgical treatment. PMID:23587156

  18. Recent advances in aortic valve replacement for aortic stenosis

    PubMed Central

    Al-Adhami, Ahmed; Al-Attar, Nawwar

    2016-01-01

    Aortic valve replacement is no longer an operation that is approached solely through a median sternotomy. Recent advances in the fields of transcatheter valves have expanded the proportion of patients eligible for intervention. Comparisons between transcatheter valves and conventional surgery have shown non-inferiority of transcatheter valve implants in patients with a high or intermediate pre-operative predictive risk. With advances in our understanding of sutureless valves and their applicability to minimally invasive surgery, the invasiveness and trauma of surgery can be reduced with potential improvements in outcome. The strategy of care has radically changed over the last decade. PMID:27803800

  19. Intraoperative tracking of aortic valve plane

    PubMed Central

    Nguyen, Duc Long Hung; Garreau, Mireille; Auffret, Vincent; Le Breton, Hervé; Verhoye, Jean-Philippe; Haigron, Pascal

    2013-01-01

    The main objective of this work is to track the aortic valve plane in intra-operative fluoroscopic images in order to optimize and secure Transcatheter Aortic Valve Implantation (TAVI) procedure. This paper is focused on the issue of aortic valve calcifications tracking in fluoroscopic images. We propose a new method based on the Tracking-Learning-Detection approach, applied to the aortic valve calcifications in order to determine the position of the aortic valve plane in intra-operative TAVI images. This main contribution concerns the improvement of object detection by updating the recursive tracker in which all features are tracked jointly. The approach has been evaluated on four patient databases, providing an absolute mean displacement error less than 10 pixels ≈ 2mm). Its suitability for the TAVI procedure has been analyzed. PMID:24110703

  20. Organ protection during aortic cross-clamping.

    PubMed

    Yeung, Kak Khee; Groeneveld, Menno; Lu, Joyce Ja-Ning; van Diemen, Pepijn; Jongkind, Vincent; Wisselink, Willem

    2016-09-01

    Open surgical repair of an aortic aneurysm requires aortic cross-clamping, resulting in temporary ischemia of all organs and tissues supplied by the aorta distal to the clamp. Major complications of open aneurysm repair due to aortic cross-clamping include renal ischemia-reperfusion injury and postoperative colonic ischemia in case of supra- and infrarenal aortic aneurysm repair. Ischemia-reperfusion injury results in excessive production of reactive oxygen species and in oxidative stress, which can lead to multiple organ failure. Several perioperative protective strategies have been suggested to preserve renal function during aortic cross-clamping, such as pharmacotherapy and therapeutic hypothermia of the kidneys. In this chapter, we will briefly discuss the pathophysiology of ischemia-reperfusion injury and the preventative measures that can be taken to avoid abdominal organ injury. Finally, techniques to minimize the risk of complications during and after open aneurysm repair will be presented. PMID:27650341

  1. Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms

    PubMed Central

    Fujii, Masayuki; Yoshimura, Koichi; Aoki, Hiroki; Orita, Yuichi; Ishida, Takafumi; Ohtaki, Megu; Nagao, Masataka; Ishida, Mari; Yoshizumi, Masao

    2016-01-01

    Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail. PMID:26783750

  2. 3D Bioprinting of Heterogeneous Aortic Valve Conduits with Alginate/Gelatin Hydrogels

    PubMed Central

    Duan, Bin; Hockaday, Laura A.; Kang, Kevin H.; Butcher, Jonathan T.

    2013-01-01

    Heart valve disease is a serious and growing public health problem for which prosthetic replacement is most commonly indicated. Current prosthetic devices are inadequate for younger adults and growing children. Tissue engineered living aortic valve conduits have potential for remodeling, regeneration, and growth, but fabricating natural anatomical complexity with cellular heterogeneity remain challenging. In the current study, we implement 3D bioprinting to fabricate living alginate/gelatin hydrogel valve conduits with anatomical architecture and direct incorporation of dual cell types in a regionally constrained manner. Encapsulated aortic root sinus smooth muscle cells (SMC) and aortic valve leaflet interstitial cells (VIC) were viable within alginate/gelatin hydrogel discs over 7 days in culture. Acellular 3D printed hydrogels exhibited reduced modulus, ultimate strength, and peak strain reducing slightly over 7-day culture, while the tensile biomechanics of cell-laden hydrogels were maintained. Aortic valve conduits were successfully bioprinted with direct encapsulation of SMC in the valve root and VIC in the leaflets. Both cell types were viable (81.4±3.4% for SMC and 83.2±4.0% for VIC) within 3D printed tissues. Encapsulated SMC expressed elevated alpha-smooth muscle actin when printed in stiff matrix, while VIC expressed elevated vimentin in soft matrix. These results demonstrate that anatomically complex, heterogeneously encapsulated aortic valve hydrogel conduits can be fabricated with 3D bioprinting. PMID:23015540

  3. Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?

    PubMed Central

    Gao, Yuan Z.; Saphirstein, Robert J.; Yamin, Rina; Suki, Bela

    2014-01-01

    Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small-molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of NG-nitro-l-arginine methyl ester (l-NAME) to remove interference of endothelial nitric oxide, increases stiffness by 90–200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which 1) VSMCs are a surprisingly large component of aortic stiffness at physiological lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors. PMID:25128168

  4. MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model.

    PubMed

    Aplin, Alfred C; Fogel, Eric; Nicosia, Roberto F

    2010-09-01

    Rings of rat or mouse aorta embedded in collagen gels produce angiogenic outgrowths in response to the injury of the dissection procedure. Aortic outgrowths are composed of branching endothelial tubes and surrounding mural cells. Mural cells emerge following endothelial sprouting and gradually increase during the maturation of the neovessels. Treatment of aortic cultures with angiopoietin-1 (Ang-1), an angiogenic factor implicated in vascular maturation and remodeling, stimulates the mural cell recruitment process. Ang-1 induces expression of many cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1). Inhibition of p38 MAP kinase, a signaling molecule required for mural cell recruitment, blocks Ang1-induced MCP-1 expression. Recombinant MCP-1 dose-dependently increases mural cell number while an anti-MCP-1 blocking antibody reduces it. In addition, antibody mediated neutralization of MCP-1 abrogates the stimulatory effect of Ang-1 on mural cell recruitment. Aortic rings from genetically modified mice deficient in MCP-1 or its receptor CCR2 have fewer mural cells than controls. MCP-1 deficiency also impairs the mural cell recruitment activity of Ang-1. Our studies indicate that spontaneous and Ang1-induced mural cell recruitment in the aortic ring of model of angiogenesis are in part mediated by MCP-1. These results implicate MCP-1 as one of the mediators of mural cell recruitment in the aortic ring model, and suggest that chemokine pathways may contribute to the assembly of the vessel wall during the angiogenesis response to injury.

  5. Successful management of para-aortic lymphocyst with laparoscopic fenestration.

    PubMed

    Sarli, L; Cortellini, P; Pavlidis, C; Simonazzi, M; Sebastio, N

    2000-04-01

    Para-aortic lymphocyst occasionally follows retroperitoneal para-aortic node dissection for neoplastic diseases. We present a case in which the leakage of chylous fluid and then a para-aortic lymphocyst followed right nephrectomy and para-aortic node dissection for kidney cancer. Our method of treatment utilized conservative management of chylous ascites and laparoscopic internal drainage of the retroperitoneal lymphocyst.

  6. 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

  7. 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.

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

    PubMed

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

    2015-07-01

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

  9. 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

  10. 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.

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

    PubMed

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

    2011-01-01

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

  12. Endovascular abdominal aortic aneurysm repair

    PubMed Central

    Norwood, M G A; Lloyd, G M; Bown, M J; Fishwick, G; London, N J; Sayers, R D

    2007-01-01

    The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique. PMID:17267674

  13. Leaking mycotic abdominal aortic aneurysm.

    PubMed

    Sing, T M; Young, N; O'Rourke, I C; Tomlinson, P

    1994-11-01

    A case of leaking mycotic abdominal aortic aneurysm is reported, with a brief review of the literature. A 58 year old female presented with shoulder and abdominal pain associated with diarrhoea, vomiting and fever with leucocytosis. Computed tomography of the abdomen showed pooling of contrast in the retroperitoneum anterior to a non-dilated abdominal aorta. There was considerable retroperitoneal blood accumulating in a mass-like lesion in the right lower abdomen and pelvis obstructing the right renal collecting system. Laparotomy revealed a 4 cm diameter saccular aneurysm of the abdominal aorta, with a 1 cm diameter neck. Culture of the thrombus grew Streptococcus pyogenes. PMID:7993259

  14. Elastin-Derived Peptides Promote Abdominal Aortic Aneurysm Formation by Modulating M1/M2 Macrophage Polarization.

    PubMed

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D; Meisinger, Trevor M; Casale, George P; Baxter, B Timothy

    2016-06-01

    Abdominal aortic aneurysm is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix degradation. Damage to elastin in the extracellular matrix results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Proinflammatory M1 macrophages initially are recruited to sites of injury, but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. Abdominal aortic aneurysm tissue reveals a high M1/M2 ratio in which proinflammatory cells and their associated markers dominate. In the current study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57BL/6 mice, Ab-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and proinflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2-polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a proinflammatory environment in aortic tissue by inducing M1 polarization, and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  15. Aortic valve and ascending aortic root modeling from 3D and 3D+t CT

    NASA Astrophysics Data System (ADS)

    Grbic, Saša; Ionasec, Razvan I.; Zäuner, Dominik; Zheng, Yefeng; Georgescu, Bogdan; Comaniciu, Dorin

    2010-02-01

    Aortic valve disorders are the most frequent form of valvular heart disorders (VHD) affecting nearly 3% of the global population. A large fraction among them are aortic root diseases, such as aortic root aneurysm, often requiring surgical procedures (valve-sparing) as a treatment. Visual non-invasive assessment techniques could assist during pre-selection of adequate patients, planning procedures and afterward evaluation of the same. However state of the art approaches try to model a rather short part of the aortic root, insufficient to assist the physician during intervention planning. In this paper we propose a novel approach for morphological and functional quantification of both the aortic valve and the ascending aortic root. A novel physiological shape model is introduced, consisting of the aortic valve root, leaflets and the ascending aortic root. The model parameters are hierarchically estimated using robust and fast learning-based methods. Experiments performed on 63 CT sequences (630 Volumes) and 20 single phase CT volumes demonstrated an accuracy of 1.45mm and an performance of 30 seconds (3D+t) for this approach. To the best of our knowledge this is the first time a complete model of the aortic valve (including leaflets) and the ascending aortic root, estimated from CT, has been proposed.

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

    PubMed Central

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

    2016-01-01

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

  17. Aortic root size and prevalence of aortic regurgitation in elite strength trained athletes.

    PubMed

    Babaee Bigi, Mohammad Ali; Aslani, Amir

    2007-08-01

    Athletes involved in mainly static or isometric exercise (e.g., weight lifting, power lifting, and bodybuilding) develop pressure overloads due to the high systemic arterial pressure found in this type of exercise. It is hypothesized that chronically elevated aortic wall tension in strength-trained athletes is associated with aortic dilatation and regurgitation. The aim of this study was to evaluate aortic root size and the prevalence of aortic regurgitation in elite strength-trained athletes. The cohort included 100 male athletes (mean age 22.1 +/- 3.6 years; all were finalists or medalists in the country) and 128 healthy age- and height-matched subjects (the control group). Aortic root diameters at end-diastole were measured at 4 locations: (1) the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction, and (4) the maximal diameter of the proximal ascending aorta. Aortic root diameters at all levels were significantly greater in the strength-trained athletes (p <0.05 for all comparisons). When the strength-trained athletes were divided into quartiles of duration of high-intensity strength training (first quartile: <18 months; second quartile: >18 and <36 months; third quartile: >36 and <54 months; fourth quartile: >54 months), progressive enlargement was found at all aortic diameters. In conclusion, aortic root diameters in all segments of the aortic root were significantly greater in elite strength-trained athletes compared with an age- and height-matched population.

  18. Nontraumatic avulsion of aortic valve commissure as a cause of acute aortic valve regurgitation

    PubMed Central

    Chang, Rei-Yeuh; Chen, Chien-Chang; Hsu, Wei-Pang; Hsiao, Pei-Ching; Tsai, Han-Lin; Hsiao, Ping-Gune; Wu, Jiann-Der; Guo, How-Ran

    2016-01-01

    Abstract Background: Avulsion of the aortic valve commissure as a cause of acute aortic valve regurgitation is mostly due to trauma, infective endocarditis, or ascending aortic dissection. Nontraumatic avulsion of the aortic valve commissure is very rare. We reviewed the literature and analyzed potential risk factors of nontraumatic avulsion. Case presentation: An 80-year-old male with hypertension was seen in the emergency department with acute onset dyspnea. Echocardiogram revealed left ventricular hypertrophy with adequate systolic function, prolapse of the noncoronary cusp, and incomplete coaptation of the right coronary and noncoronary cusps with severe aortic valve regurgitation. Surgery revealed an avulsion between the left coronary and noncoronary cusps. Histopathology examination of the aortic valve showed myxoid degeneration, fibrosis, and calcification. Examination of the ascending aorta revealed myxoid degeneration and fragmentation of elastic fibers. Aortic valve replacement was performed, and the patient was alive and well 4 years after surgery. A review of the literature showed that more than three-fourths of the similar cases occurred in males, and about half in patients with hypertension and those 60 years of age or older. Conclusions: In the case of acute aortic regurgitation without a history of trauma, infection, or valvotomy, when 2 prolapsed aortic cusps are observed by echocardiography in the absence of an intimal tear of the ascending aorta, an avulsion of the aortic commissure should be suspected, especially in males with hypertension who are 60 years of age or older. PMID:27749570

  19. 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

  20. Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model.

    PubMed

    Nunes, Ana Karolina Santana; Rapôso, Catarina; Rocha, Sura Wanessa Santos; Barbosa, Karla Patrícia de Sousa; Luna, Rayana Leal de Almeida; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves

    2015-11-19

    Sildenafil (Viagra®) has recently been found to have a neuroprotective effect, which occurs through the inhibition of inflammation and demyelination in the cerebellum. However, the mechanism of action of sildenafil remains unknown. AMPK, the regulatory protein of the lipid and glucose metabolism, plays a protective role by activating the eNOS enzyme. The production of a nanomolar concentration of NO by eNOS has an anti-inflammatory effect through the cGMP signaling pathway and plays an important role in the regulation of the nuclear transcription factor (NFkB), preventing the expression of inflammatory genes. The present study investigated whether AMPK-eNOS-NO-cGMP-IКβα-NFkB is involved in the mechanism of action of sildenafil in a cuprizone-demyelination model. Neuroinflammation and demyelination induced by cuprizone in rodents have been widely used as a model of MS. In the present study, five male C57BL/6 mice (7-10 weeks old) were used. Over a four week period, the groups received: cuprizone (CPZ) 0.2% mixed in feed; CPZ in the diet, combined with the administration of sildenafil (Viagra®, Pfizer, 25mg/kg) orally in drinking water, starting concurrently (sild-T0) or 15 days (sild-T15) after the start of CPZ. Control animals received pure food and water. The cerebella of the mice were dissected and processed for immunohistochemistry, immunofluorescence (frozen), western blotting and dosage of cytokines (Elisa). CPZ induced an increase in the expression of GFAP, IL-1β TNF-α, total NFkB and inactive AMPK, and prompt microglia activation. CPZ also induced a reduction of IKβα. The administration of sildenafil reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α and increased the expression of the anti-inflammatory cytokine IL-10. In addition, the administration of sildenafil reduced expression of GFAP, NFkB, inactive AMPK and iNOS, and increased IKβα. Interestingly, sildenafil also reduced levels of NGF. In general, the sild-T0 group

  1. Comparison of magnetic resonance imaging of aortic valve stenosis and aortic root to multimodality imaging for selection of transcatheter aortic valve implantation candidates.

    PubMed

    Paelinck, Bernard P; Van Herck, Paul L; Rodrigus, Inez; Claeys, Marc J; Laborde, Jean-Claude; Parizel, Paul M; Vrints, Christiaan J; Bosmans, Johan M

    2011-07-01

    The purpose of the present study was to compare the aortic valve area, aortic valve annulus, and aortic root dimensions measured using magnetic resonance imaging (MRI) with catheterization, transthoracic echocardiography (TTE), and transesophageal echocardiography (TEE). An optimal prosthesis--aortic root match is an essential goal when evaluating patients for transcatheter aortic valve implantation. Comparisons between MRI and the other imaging techniques are rare and need validation. In 24 consecutive, high-risk, symptomatic patients with severe aortic stenosis, aortic valve area was prospectively determined using MRI and direct planimetry using three-dimensional TTE and calculated by catheterization using the Gorlin equation and by Doppler echocardiography using the continuity equation. Aortic valve annulus and the aortic root dimensions were prospectively measured using MRI, 2-dimensional TTE, and invasive aortography. In addition, aortic valve annulus was measured using TEE. No differences in aortic valve area were found among MRI, Doppler echocardiography, and 3-dimensional TTE compared with catheterization (p = NS). Invasive angiography underestimated aortic valve annulus compared with MRI (p <0.001), TEE (p <0.001), and 2-dimensional TTE (p <0.001). Two-dimensional TTE tended to underestimate the aortic valve annulus diameters compared to TEE and MRI. In contrast to 2-dimensional TTE, 3 patients had aortic valve annulus beyond the transcatheter aortic valve implantation range using TEE and MRI. In conclusion, MRI planimetry, Doppler, and 3-dimensional TTE provided an accurate estimate of the aortic valve area compared to catheterization. MRI and TEE provided similar and essential assessment of the aortic valve annulus dimensions, especially at the limits of the transcatheter aortic valve implantation range.

  2. Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

    PubMed

    Gu, Qi; Wang, Bing; Zhang, Xiao-Feng; Ma, Yan-Ping; Liu, Jian-Dong; Wang, Xiao-Ze

    2014-08-01

    Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging.

  3. Serum and tissue biomarkers in aortic stenosis

    PubMed Central

    Kapelouzou, Alkistis; Tsourelis, Loukas; Kaklamanis, Loukas; Degiannis, Dimitrios; Kogerakis, Nektarios; Cokkinos, Dennis V.

    2015-01-01

    Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. Methods: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor β1 (TGF-β1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. Results: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1

  4. Acacetin inhibits in vitro and in vivo angiogenesis and down-regulates Stat signaling and VEGF expression

    PubMed Central

    Bhat, Tariq A.; Nambiar, Dhanya; Tailor, Dhanir; Pal, Arttatrana; Agarwal, Rajesh; Singh, Rana P.

    2013-01-01

    Angiogenesis is an effective target in cancer control. The anti-angiogenic efficacy and associated mechanisms of acacetin, a plant flavone, is poorly known. In the present study, acacetin inhibited growth and survival (upto 92%, p<0.001), and capillary-like tube formation on matrigel (upto 98%, p<0.001) by human umbilical vein endothelial cells (HUVEC) in regular condition, as well as VEGF-induced and tumor cells conditioned medium-stimulated growth conditions. It caused retraction and disintegration of preformed capillary networks (upto 91%, p<0.001). HUVEC migration and invasion were suppressed by 68-100% (p<0.001). Acacetin inhibited Stat-1 (Tyr701) and Stat-3 (Tyr705) phosphorylation, and down-regulated pro-angiogenic factors including VEGF, eNOS, iNOS, MMP-2 and bFGF in HUVEC. It also suppressed nuclear localization of pStat-3 (Tyr705). Acacetin strongly inhibited capillary sprouting and networking from rat aortic rings and fertilized chicken egg chorioallantoic membrane (CAM) (~71%, p<0.001). Furthermore, it suppressed angiogenesis in matrigel plugs implanted in Swiss albino mice. Acacetin also inhibited tyrosine phosphorylation of Stat-1 and Stat-3, and expression of VEGF in cancer cells. Overall, acacetin inhibits Stat signaling and suppresses angiogenesis in vitro, ex vivo and in vivo, and therefore, it could be a potential agent to inhibit tumor angiogenesis and growth. PMID:23943785

  5. Possible Dual Role of Decorin in Abdominal Aortic Aneurysm

    PubMed Central

    Ueda, Koshiro; Yoshimura, Koichi; Yamashita, Osamu; Harada, Takasuke; Morikage, Noriyasu; Hamano, Kimikazu

    2015-01-01

    Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP)-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion. PMID:25781946

  6. 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.

  7. 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

  8. Recurrent Rare Genomic Copy Number Variants and Bicuspid Aortic Valve Are Enriched in Early Onset Thoracic Aortic Aneurysms and Dissections

    PubMed Central

    Prakash, Siddharth; Kuang, Shao-Qing; Regalado, Ellen; Guo, Dongchuan; Milewicz, Dianna

    2016-01-01

    Thoracic Aortic Aneurysms and Dissections (TAAD) are a major cause of death in the United States. The spectrum of TAAD ranges from genetic disorders, such as Marfan syndrome, to sporadic isolated disease of unknown cause. We hypothesized that genomic copy number variants (CNVs) contribute causally to early onset TAAD (ETAAD). We conducted a genome-wide SNP array analysis of ETAAD patients of European descent who were enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Genotyping was performed on the Illumina Omni-Express platform, using PennCNV, Nexus and CNVPartition for CNV detection. ETAAD patients (n = 108, 100% European American, 28% female, average age 20 years, 55% with bicuspid aortic valves) were compared to 7013 dbGAP controls without a history of vascular disease using downsampled Omni 2.5 data. For comparison, 805 sporadic TAAD patients with late onset aortic disease (STAAD cohort) and 192 affected probands from families with at least two affected relatives (FTAAD cohort) from our institution were screened for additional CNVs at these loci with SNP arrays. We identified 47 recurrent CNV regions in the ETAAD, FTAAD and STAAD groups that were absent or extremely rare in controls. Nine rare CNVs that were either very large (>1 Mb) or shared by ETAAD and STAAD or FTAAD patients were also identified. Four rare CNVs involved genes that cause arterial aneurysms when mutated. The largest and most prevalent of the recurrent CNVs were at Xq28 (two duplications and two deletions) and 17q25.1 (three duplications). The percentage of individuals harboring rare CNVs was significantly greater in the ETAAD cohort (32%) than in the FTAAD (23%) or STAAD (17%) cohorts. We identified multiple loci affected by rare CNVs in one-third of ETAAD patients, confirming the genetic heterogeneity of TAAD. Alterations of candidate genes at these loci may contribute to the pathogenesis of TAAD. PMID:27092555

  9. Genome-wide association study using a high-density SNP-array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of eNOS

    PubMed Central

    Salvi, Erika; Kutalik, Zoltán; Glorioso, Nicola; Benaglio, Paola; Frau, Francesca; Kuznetsova, Tatiana; Arima, Hisatomi; Hoggart, Clive; Tichet, Jean; Nikitin, Yury P.; Conti, Costanza; Seidlerova, Jitka; Tikhonoff, Valérie; Stolarz-Skrzypek, Katarzyna; Johnson, Toby; Devos, Nabila; Zagato, Laura; Guarrera, Simonetta; Zaninello, Roberta; Calabria, Andrea; Stancanelli, Benedetta; Troffa, Chiara; Thijs, Lutgarde; Rizzi, Federica; Simonova, Galina; Lupoli, Sara; Argiolas, Giuseppe; Braga, Daniele; D’Alessio, Maria C.; Ortu, Maria F.; Ricceri, Fulvio; Mercurio, Maurizio; Descombes, Patrick; Marconi, Maurizio; Chalmers, John; Harrap, Stephen; Filipovsky, Jan; Bochud, Murielle; Iacoviello, Licia; Ellis, Justine; Stanton, Alice V.; Laan, Maris; Padmanabhan, Sandosh; Dominiczak, Anna F.; Samani, Nilesh J.; Melander, Olle; Jeunemaitre, Xavier; Manunta, Paolo; Shabo, Amnon; Vineis, Paolo; Cappuccio, Francesco P.; Caulfield, Mark J.; Matullo, Giuseppe; Rivolta, Carlo; Munroe, Patricia B.; Barlassina, Cristina; Staessen, Jan A; Beckmann, Jacques S.; Cusi, Daniele

    2012-01-01

    Essential hypertension is a multi-factorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a two-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1,865 cases and 1,750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1,385 cases and 1,246 controls that were genotyped with a custom array of 14,055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial nitric oxide synthase (eNOS) gene (odds ratio 1.54; 95% CI 1.37-1.73; combined p=2.58·10−13). A meta-analysis, using other in-silico/de novo genotyping data for a total of 21714 subjects, resulted in an overall odds ratio of 1.34 (95% CI 1.25-1.44, p=1.032·10−14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI 0.16-3.66) for systolic and 1.40 (95% CI 0.25-2.55) for diastolic blood pressure. We identified in-silico a potential binding site for ETS transcription-factors directly next to rs3918226, suggesting a potential modulation of eNOS expression. Biological evidence links eNOS with hypertension, as it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus. PMID:22184326

  10. 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

  11. 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

  12. Pathology specific secondary aortic interventions after thoracic endovascular aortic repair

    PubMed Central

    Scali, Salvatore T.; Beck, Adam W.; Butler, Khayree; Feezor, Robert J.; Martin, Tomas D.; Hess, Philip J.; Huber, Thomas S.; Chang, Catherine K.

    2014-01-01

    Objective: Despite improved short-term outcomes, concerns remain regarding durability of thoracic endovascular aortic repair(TEVAR). The purpose of this analysis was to evaluate the pathology-specific incidence of secondary aortic interventions(SAI) after TEVAR and their impact on survival. Methods: Retrospective review was performed of all TEVAR procedures and SAI at one institution from 2004-2011. Kaplan-Meier analysis was used to estimate survival. Results: Of 585 patients, 72(12%) required SAI at a median of 5.6 months(interquartile range(IQR):1.4-14.2) with 22(3.7%) requiring multiple SAI. SAI incidence differed significantly by pathology(P=.002): acute dissection(21.3%), post-surgical(20.0%), chronic dissection(16.7%), degenerative aneurysm(10.8%), traumatic transection(8.1%), penetrating ulcer(1.5%), and other etiologies(14.8%). Most common indications after dissection were persistent false lumen flow and proximal/distal extension of disease. For degenerative aneurysms, SAI was performed primarily to treat type I/III endoleaks. SAI patients had a greater mean number of comorbidities(P<.0005), stents placed(P=.0002), and postoperative complications after the index TEVAR(P<.0005) compared to those without SAI. Freedom from SAI at 1 and 5 years(95% CI) was estimated to be 86%(82-90%) and 68%(57-76%), respectively. There were no differences in survival(95% CI) between patients requiring SAI and those who did not: SAI 1-year: 88%(77-93%), 5-year: 51%(37-63%) and no SAI 1-year: 82%(79-85%), 5-year: 67%(62-71%)(Log-rank P=0.2). Conclusion: SAI after TEVAR is not uncommon, particularly in patients with dissection, but does not affect long-term survival. Aortic pathology is the most important variable impacting survival and dictated need, timing and mode of SAI. The varying incidence of SAI by indication underscores the need for diligent surveillance protocols that should be pathology-specific. PMID:24571937

  13. ACTIVATION OF VASCULAR ENDOTHELIAL NITRIC OXIDE SYNTHASE AND HEME OXYGENASE-1 EXPRESSION BY ELECTROPHILIC NITRO-FATTY ACIDS

    PubMed Central

    Khoo, Nicholas K.H.; Rudolph, Volker; Cole, Marsha P.; Golin-Bisello, Franca; Schopfer, Francisco J.; Woodcock, Steven R.; Batthyany, Carlos; Freeman, Bruce A.

    2010-01-01

    Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability and endothelial dysfunction, with secondary oxidized and nitrated byproducts of these reactions contributing to the pathogenesis of numerous vascular diseases. While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the vasculature, in stark contrast the nitration of polyunsaturated fatty acids and complex lipids yield electrophilic products that exhibit pluripotent anti-inflammatory signaling capabilities acting via both cGMP-dependent and -independent mechanisms. Herein we report that nitro-oleic acid (OA-NO2) treatment increases expression of endothelial nitric oxide synthase (eNOS) and heme oxygenase 1 (HO-1) in the vasculature, thus transducing vascular protective effects associated with enhanced NO production. Administration of OA-NO2 via osmotic pump results in a significant increase in eNOS and HO-1 mRNA in mouse aortas. Moreover, HPLC-MS/MS analysis showed that NO2-FAs are rapidly metabolized in cultured endothelial cells (ECs) and treatment with NO2-FAs stimulated the phosphorylation of eNOS at Ser1179. These post-translational modifications of eNOS, in concert with elevated eNOS gene expression, contributed to an increase in endothelial NO production. In aggregate, OA-NO2-induced eNOS and HO-1 expression by vascular cells can induce beneficial effects on endothelial function and provide a new strategy for treating various vascular inflammatory and hypertensive disorders. PMID:19857569

  14. Transcatheter aortic valve implantation: anesthetic considerations.

    PubMed

    Billings, Frederic T; Kodali, Susheel K; Shanewise, Jack S

    2009-05-01

    Aortic valvular stenosis remains the most common debilitating valvular heart lesion. Despite the benefit of aortic valve (AV) replacement, many high-risk patients cannot tolerate surgery. AV implantation treats aortic stenosis without subjecting patients to sternotomy, cardiopulmonary bypass (CPB), and aorta cross-clamping. This transcatheter procedure is performed via puncture of the left ventricular (LV) apex or percutaneously, via the femoral artery or vein. Patients undergo general anesthesia, intense hemodynamic manipulation, and transesophageal echocardiography (TEE). To elucidate the role of the anesthesiologist in the management of transcatheter AV implantation, we review the literature and provide our experience, focusing on anesthetic care, intraoperative events, TEE, and perioperative complications. Two approaches to the aortic annulus are performed today: transfemoral retrograde and transapical antegrade. Iliac artery size and tortuosity, aortic arch atheroma, and pathology in the area of the (LV) apex help determine the preferred approach in each patient. A general anesthetic is tailored to achieve extubation after procedure completion, whereas IV access and pharmacological support allow for emergent sternotomy and initiation of CPB. Rapid ventricular pacing and cessation of mechanical ventilation interrupts cardiac ejection and minimizes heart translocation during valvuloplasty and prosthesis implantation. Although these maneuvers facilitate exact prosthesis positioning within the native annulus, they promote hypotension and arrhythmia. Vasopressor administration before pacing and cardioversion may restore adequate hemodynamics. TEE determines annulus size, aortic pathology, ventricular function, and mitral regurgitation. TEE and fluoroscopy are used for positioning the introducer catheter within the aortic annulus. The prosthesis, crimped on a valvuloplasty balloon catheter, is implanted by inflation. TEE immediately measures aortic regurgitation and

  15. 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

  16. Giant aortic arch aneurysm complicating Kawasaki's disease

    PubMed Central

    Hakim, Kaouthar; Boussada, Rafik; Chaker, Lilia; Ouarda, Fatma

    2014-01-01

    Kawasaki disease (KD) is a common acute vasculitis in pediatric population that usually involves small- and middle-sized arteries, commonly coronary arteries. Although the incidence and natural course of coronary aneurysms after KD are well documented in studies, related reports on peripheral arterial and aortic aneurysms are scarce. We report the occurrence of a giant aortic aneurysm involving the horizontal part of aortic arch in a 28-month-old boy diagnosed with KD. This complication was managed by steroids therapy in the beginning. Because of mechanical complication and potential risk of rupture, surgery was undertaken. PMID:25298695

  17. Bacillus cereus endocarditis in native aortic valve.

    PubMed

    Ngow, H A; Wan Khairina, W M N

    2013-02-01

    Bacillus cereus endocarditis is rare. It has been implicated in immunocompromised individuals, especially in intravenous drug users as well as in those with a cardiac prosthesis. The patient was a 31-year-old ex-intravenous drug addict with a past history of staphylococcal pulmonary valve endocarditis, who presented with symptoms of decompensated cardiac failure. Echocardiography showed severe aortic regurgitation with an oscillating vegetation seen on the right coronary cusp of the aortic valve. The blood cultures grew Bacillus cereus. We report this as a rare case of Bacillus cereus endocarditis affecting a native aortic valve.

  18. [Infrarenal aortic pseudo-aneurism due to Coxiella burnetii].

    PubMed

    Paumier, A; Penard, J; Maugin, E; Enon, B; Picquet, J

    2007-12-01

    Peripheral vascular expressions of Coxiella burnetti Q fever are not well known. Endocarditis with negative blood culture is the most frequent clinical presentation of chronic Q fever. To date, very few cases of aneurisms or vascular grafts infections have been described. We report the case of a 54-year-old man who presented an infrarenal abdominal aorta infection, leading to a giant pseudo aneurismal formation. Blood serology and polymerase chain reaction amplification identified C. burnetti from the aortic thrombus after pseudo aneurism surgery. The treatment associated infrarenal abdominal aorta repair using a cryopreserved aorta allograft, and long-term antibiotic therapy. PMID:17851006

  19. 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

  20. Descending aortic dissection injured by tip of the sheath during transcatheter aortic valve implantation.

    PubMed

    Nagasawa, Atsushi; Shirai, Shinichi; Hanyu, Michiya; Arai, Yoshio; Kamioka, Norihiko; Hayashi, Masaomi

    2016-04-01

    An 86-year-old woman was referred for transcatheter aortic valve implantation (TAVI) because of recurrent severe aortic stenosis after balloon aortic valvuloplasty in May 2014. We planned to implant a 23-mm Sapien XT valve by transfemoral approach. During procedure, aortic dissection was detected by transesophageal echocardiography (TEE). The dissection limited to the descending aorta and did not include the ascending aorta. Therefore, our team decided to implant the 23-mm Sapien valve as planned. After the procedure, the dissection was treated conservatively without surgical repair. Three weeks later, she was discharged without any complications.

  1. Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

    PubMed Central

    Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M. A.; van Heijningen, Paula M.; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M.; van Esch, Joep H. M.; Lankhorst, Stephanie; Ramnath, Natasja W. M.; de Waard, Monique C.; Duncker, Dirk J.; van der Spek, Peter J.; Rouwet, Ellen V.; Danser, A. H. Jan; Essers, Jeroen

    2011-01-01

    Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-β signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-β. Tissue levels of Ang II, a regulator of TGF-β signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-β signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of

  2. Endovascular Aortic Repair of Primary Adult Coarctation: Implications and Challenges for Postoperative Nursing.

    PubMed

    Sheppard, Christina E; Then, Karen L; Rankin, James A; Appoo, Jehangir J

    2015-01-01

    Endovascular aortic repair is a relatively new surgical technique used to treat a variety of aortic pathologies. Aortic coarctation traditionally has been managed with open surgical repair, involving a large posterolateral thoracotomy, cardiopulmonary bypass, and replacement of the narrowed section of the aorta with a dacron graft. Recent advances in minimally invasive aortic surgery have allowed for repair of the diseased section with an endovascular stent placed percutaneously through the groin under intraoperative fluoroscopic guidance. In this paper, the authors willfocus on the implicationsfor postoperative nursing care after endovascular repair of aortic coarctation using a case study of a 17-year-old male. This novel technique required education of the health care team with respect to implications for practice, understanding potential complications, discharge planning and follow-up. With any new surgical technique there are many questions and challenges that health care professionals raise. The main concerns expressed from the health care team stemmed from a lack of understanding of the disease pathology, and the different risk profile associated with an endovascular repair in contrast to an open repair. The authors will address these concerns in detail.

  3. Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke.

    PubMed

    Altura, Burton M; Kostellow, Adele B; Zhang, Aimin; Li, Wenyan; Morrill, Gene A; Gupta, Raj K; Altura, Bella T

    2003-09-01

    Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.

  4. [Mechanism of losartan suppressing vascular calcification in rat aortic artery].

    PubMed

    Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

    2016-08-01

    Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID:27412937

  5. Valve selection in aortic valve endocarditis

    PubMed Central

    Zubrytska, Yana

    2016-01-01

    Aortic prosthetic valve endocarditis (PVE) is a potentially life-threatening disease. Mortality and incidence of infective endocarditis have been reduced in the past 30 years. Medical treatment of aortic PVE may be successful in patients who have a prompt response after antibiotic treatment and who do not have prosthetic dysfunction. In advanced stages, antibiotic therapy alone is insufficient to control the disease, and surgical intervention is necessary. Surgical treatment may be lifesaving, but it is still associated with considerable morbidity and mortality. The aim of surgery is to perform a radical excision of all infected and necrotic tissue, reconstruction of the left ventricle outflow tract, and replacement of the aortic valve. There is no unanimous consensus on which is the optimal prosthesis to implant in this context, and several surgical techniques have been suggested. We aim to analyze the efficacy of the surgical treatment and discuss the issue of valve selection in patients with aortic valve endocarditis. PMID:27785132

  6. 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

  7. The diagnosis and management of aortic dissection.

    PubMed

    Karthikesalingam, A; Holt, P J E; Hinchliffe, R J; Thompson, M M; Loftus, I M

    2010-04-01

    Aortic dissection represents the most common aortic emergency, affecting 3 to 4 per 100,000 people per year and is still associated with a high mortality. Twenty percent of the patients with aortic dissection die before reaching hospital and 30% die during hospital admission. Aortic dissections may be classified in 3 ways: according to their anatomical extent (the Stanford or DeBakey systems), according to the time from onset (acute or chronic), and according to the underlying pathology (the European Society of Cardiologists' system). Advances in endovascular technology have provided new treatment options. Hybrid endovascular and conventional open surgical repair represent the mainstay of treatment for acute type A dissection. Medical management remains the gold standard for acute and uncomplicated chronic type B dissection, though endovascular surgery offers exciting potential in the management of complicated type B dissection through sealing of the intimal entry tear.

  8. 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

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

    PubMed Central

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

    2015-01-01

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

  10. 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.

  11. Abdominal Aortic Aneurysmectomy in Renal Transplant Patients

    PubMed Central

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

    1990-01-01

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

  12. 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

  13. Juxtarenal aortic aneurysm: endoluminal transfemoral repair?

    PubMed

    Ferko, A; Krajina, A; Jon, B; Lesko, M; Voboril, Z; Zizka, J; Eliás, P

    1997-01-01

    Endoluminal transfemoral repair of an abdominal aortic aneurysm by a stent graft placement requires a segment of the nondilated infrarenal aorta of at least 15 mm long for safe stent graft attachment. The possibility of endoluminal treatment of a juxtarenal abdominal aortic aneurysm with partially covered spiral Z stent was assessed in experiment and in three clinical cases. In the experiment, the noncovered spiral Z stent was placed into the abdominal aorta, across the origins of renal arteries and mesenteric arteries, in six dogs. In the clinical cases, a partially covered stent graft was attached in 3 patients with the juxtarenal abdominal aortic aneurysm (of the group of 12 patients with abdominal aortic aneurysm). The stent grafts were attached with proximal uncovered parts across the origins of the renal arteries. In experiment, the renal artery occlusions or stenoses were not observed 36 months after stent placement, and in clinic, 3 patients with the juxtarenal aortic aneurysm were successfully treated by stent graft placement. There were no signs of flow impairment into the renal arteries 14 months after stent graft implantation. This approach can possibly expand the indications for endoluminal grafting in the treatment of juxtarenal aortic aneurysms in patients who are at high risk for surgery.

  14. Quantification of abdominal aortic deformation after EVAR

    NASA Astrophysics Data System (ADS)

    Demirci, Stefanie; Manstad-Hulaas, Frode; Navab, Nassir

    2009-02-01

    Quantification of abdominal aortic deformation is an important requirement for the evaluation of endovascular stenting procedures and the further refinement of stent graft design. During endovascular aortic repair (EVAR) treatment, the aortic shape is subject to severe deformation that is imposed by medical instruments such as guide wires, catheters, and, the stent graft. This deformation can affect the flow characteristics and morphology of the aorta which have been shown to be elicitors for stent graft failures and be reason for reappearance of aneurysms. We present a method for quantifying the deformation of an aneurysmatic aorta imposed by an inserted stent graft device. The outline of the procedure includes initial rigid alignment of the two abdominal scans, segmentation of abdominal vessel trees, and automatic reduction of their centerline structures to one specified region of interest around the aorta. This is accomplished by preprocessing and remodeling of the pre- and postoperative aortic shapes before performing a non-rigid registration. We further narrow the resulting displacement fields to only include local non-rigid deformation and therefore, eliminate all remaining global rigid transformations. Finally, deformations for specified locations can be calculated from the resulting displacement fields. In order to evaluate our method, experiments for the extraction of aortic deformation fields are conducted on 15 patient datasets from endovascular aortic repair (EVAR) treatment. A visual assessment of the registration results and evaluation of the usage of deformation quantification were performed by two vascular surgeons and one interventional radiologist who are all experts in EVAR procedures.

  15. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    PubMed Central

    Hua-Huy, Thông; Duong-Quy, Sy; Pham, Hoa; Pansiot, Julien; Mercier, Jean-Christophe; Baud, Olivier

    2016-01-01

    Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  16. Direct aortic transcatheter valve implantation in a porcelain aorta.

    PubMed

    Bruschi, Giuseppe; Botta, Luca; De Marco, Federico; Colombo, Paola; Klugmann, Silvio; Martinelli, Luigi

    2014-10-01

    Transcatheter aortic valve implantation has been designed to treat elderly patients with severe aortic stenosis at high risk for surgery, and is generally performed retrogradely with vascular access. However, in certain patients, this access is either not possible or deemed to carry a high risk of vascular injury. We report our experience of a direct aortic approach in a 78-year old man with severe aortic stenosis, excluded from standard aortic valve replacement due to a porcelain aorta, and affected by severe aortic, iliac-femoral, and subclavian arteriopathy, rendering the transfemoral or subclavian approach unemployable.

  17. Chest radiography in acute aortic syndrome: pearls and pitfalls.

    PubMed

    Chawla, Ashish; Rajendran, Surendran; Yung, Wai Heng; Babu, Suresh Balasubramanian; Peh, Wilfred C

    2016-08-01

    Acute aortic syndrome is a group of life-threatening diseases of the thoracic aorta that usually present to the emergency department. It includes aortic dissection, aortic intramural hematoma, and penetrating aortic ulcer. Rare aortic pathologies of aorto-esophageal fistula and mycotic aneurysm may also be included in this list. All these conditions require urgent treatment with complex clinical care and management. Most patients who present with chest pain are evaluated with a chest radiograph in the emergency department. It is important that maximum diagnostic information is extracted from the chest radiograph as certain signs on the chest radiograph are extremely useful in pointing towards the diagnosis of acute aortic syndrome.

  18. Valve sparing: aortic root replacement with the reimplantation technique.

    PubMed

    Mastrobuoni, Stefano; Tamer, Sadallah; de Kerchove, Laurent; El Khoury, Gebrine

    2015-01-01

    Aortic valve-sparing procedures are alternative options to aortic valve replacement in patients with aortic root aneurysm and/or severe aortic regurgitation reducing the risk of prosthesis-related complications, such as thromboembolism, and have no need for long-term oral anticoagulation. However, these techniques are technically demanding and long-term results are highly dependent on perfect intraoperative restoration of valve function. We describe a systematic approach to aortic valve-sparing aortic root replacement with the reimplantation technique the way it is currently performed in our institution. PMID:26137865

  19. Identification and refinement of two strong constitutive promoters for gene expression system of Schizosaccharomyces pombe.

    PubMed

    Wang, Hongcheng; Wang, Haiyang; Wang, Meng; Zhang, Lei; Wang, Ren; Mei, Yanzhen; Shao, Weilan

    2014-06-01

    Fission yeast Schizosaccharomyces pombe shares various important properties with higher eukaryotes and is now considered a useful host for elevated production of mammalian proteins for medicinal applications. The full-length nmt1 promoter has been widely used as a strong promoter in S. pombe expression system. In the present study, the promoters of the eno101 and gpd3 genes in S. pombe were identified as strong constitutive promoters. For convenient applications in the plasmids of S. pombe, these promoters were refined to 276-bp eno and 273-bp gpd promoters by deleting undesired sequences and examining the expression of reporter genes including lacZ and xynA. Both the refined eno and gpd promoters provided approximately 1.5-fold higher expression of LacZ than nmt1 promoter. Furthermore, gene expression under the control of the eno or gpd promoter was not repressed by the components of YES medium while nmt1 promoter was inhibited by thiamine in yeast extract. Therefore, both eno and gpd promoters offer opportunities for efficient production of recombinant proteins by S. pombe in high cell-density fermentation.

  20. Aortic root dissection. Another cause of early systolic closure of the aortic valve.

    PubMed Central

    Candell-Riera, J; del Castillo, H G; Rius, J

    1980-01-01

    An early systolic closure of the aortic valve was recorded in the echocardiogram in two patients with aortic root dissection. This sign, initially described in discrete subaortic stenosis and occasionally observed in mitral regurgitation and interventricular septal defect, has not so far been described in dissecting aneurysm of the aorta. Images PMID:7378219

  1. 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

  2. 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 phosphorylation of AMPK was unaffected. Down-regulation of PECAM-1 using a siRNA approach attenuated the shear-stress-induced phosphorylation of Akt and eNOS, as well as the shear-stress-induced accumulation of cyclic GMP levels while the shear-stress-induced phosphorylation of AMPK remained intact. A comparable attenuation of Akt and eNOS (but not AMPK) phosphorylation and NO production was also observed in endothelial cells generated from PECAM-1-deficient mice. These data indicate that the shear-stress-induced activation of Akt and eNOS in endothelial cells is modulated by the tyrosine phosphorylation of PECAM-1 whereas the shear-stress-induced phosphorylation of AMPK is controlled by an alternative signaling pathway. PMID:16118242

  3. 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

  4. 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

  5. [Surgical Outcomes of Aortic Root Repair in Type A Acute Aortic Dissection].

    PubMed

    Okamoto, Yuki; Yamamoto, Kazuo; Asami, Fuyuki; Kimura, Mitsuhiro; Mizumoto, Masahiro; Okubo, Yuka; Takesue, Yuki; Yoshii, Sinpei

    2016-04-01

    We carried out a retrospective evaluation of the early and long-term outcomes of aortic root reconstruction for type A acute aortic dissection. Between January 2001 and March 2015, a total of 21 patients underwent aortic root reconstruction. Bentall operation was performed in 9 patients( B group) and Patch plasty of sinus of Valsalva patients was performed in 12 patients (V group). There were 3 in-hospital deaths due in the B group and 1 death due in the V group. Overall survival in the V group was 72.9% and was not significantly different from survival in the B group(66.7%). In conclusion, our study demonstrated good early and long-term outcomes for patch plasty of sinus of Valsalva for type A acute aortic dissection. There was no postoperative patch-related complication in the V group. Thus, a patch plasty of sinus of Valsalva for type A acute aortic issection may be acceptable. PMID:27210253

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

    PubMed

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

    2015-02-15

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

  7. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    PubMed

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. PMID:26453330

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

    PubMed

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

    2015-03-01

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

  9. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-10-01

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

  12. Polymorphisms in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) predict sunitinib-induced hypertension.

    PubMed

    Eechoute, K; van der Veldt, A A M; Oosting, S; Kappers, M H W; Wessels, J A M; Gelderblom, H; Guchelaar, H-J; Reyners, A K L; van Herpen, C M L; Haanen, J B; Mathijssen, R H J; Boven, E

    2012-10-01

    Hypertension is an important side effect of sunitinib treatment. In a retrospective study in 255 patients, single-nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor (VEGFR)-2, endothelin-1 (ET-1), and endothelium-derived nitric oxide synthase (eNOS) were multivariately tested against hypertension grades and changes in systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial BP (MAP). Next, the association between hypertension and survival in patients with metastatic renal cell cancer (mRCC) was studied. Greater elevations in SBP and MAP were associated with the presence of a haplotype in VEGFA (P = 0.014 and P = 0.036, respectively). The tendency to develop grade 3 hypertension was associated with this haplotype and also with a SNP in eNOS (P = 0.031 and P = 0.045, respectively). In mRCC patients, sunitinib-induced hypertension was found to confer a survival benefit, with the mean overall survival being prolonged by 7.2 months (P = 0.035 and P = 0.026 for SBP and DBP elevations, respectively). Genetic polymorphisms in VEGFA and eNOS independently predict rise in BP and/or development of severe hypertension in sunitinib-treated patients. Grade 3 hypertension was found to be an independent factor for overall survival in patients with mRCC. PMID:22948895

  13. Genetically alike Syrian hamsters display both bifoliate and trifoliate aortic valves.

    PubMed

    Sans-Coma, Valentín; Carmen Fernández, M; Fernández, Borja; Durán, Ana C; Anderson, Robert H; Arqué, Josep M

    2012-01-01

    The bifoliate, or bicuspid, aortic valve (BAV) is the most frequent congenital cardiac anomaly in man. It is a heritable defect, but its mode of inheritance remains unclear. Previous studies in Syrian hamsters showed that BAVs with fusion of the right and left coronary leaflets are expressions of a trait, the variation of which takes the form of a phenotypic continuum. It ranges from a trifoliate valve with no fusion of the coronary leaflets to a bifoliate root devoid of any raphe. The intermediate stages are represented by trifoliate valves with fusion of the coronary aortic leaflets, and bifoliate valves with raphes. The aim of this study was to elucidate whether the distinct morphological variants rely on a common genotype, or on different genotypes. We examined the aortic valves from 1 849 Syrian hamsters belonging to a family subjected to systematic inbreeding by full-sib mating. The incidence of the different trifoliate aortic valve (TAV) and bifoliate aortic valve (BAV) morphological variants widely varied in the successive inbred generations. TAVs with extensive fusion of the leaflets, and BAVs, accounted for five-sixths of the patterns found in Syrian hamsters considered to be genetically alike or virtually isogenic, with the probability of homozygosity being 0.999 or higher. The remaining one-sixth hamsters had aortic valves with a tricuspid design, but in most cases the right and left coronary leaflets were slightly fused. Results of crosses between genetically alike hamsters, with the probability of homozygosity being 0.989 or higher, revealed no significant association between the valvar phenotypes in the parents and their offspring. Our findings are consistent with the notion that the BAVs of the Syrian hamster are expressions of a quantitative trait subject to polygenic inheritance. They suggest that the genotype of the virtually isogenic animals produced by systematic inbreeding greatly predisposes to the development of anomalous valves, be they

  14. Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms.

    PubMed Central

    Koch, A. E.; Kunkel, S. L.; Pearce, W. H.; Shah, M. R.; Parikh, D.; Evanoff, H. L.; Haines, G. K.; Burdick, M. D.; Strieter, R. M.

    1993-01-01

    Inflammatory leukocytes play a central role in the pathogenesis of human atherosclerotic disease, from early atherogenesis to the late stages of atherosclerosis, such as aneurysm formation. We have shown previously that human abdominal aortic aneurysms are characterized by the presence of numerous chronic inflammatory cells throughout the vessel wall (Am J Pathol 1990, 137: 1199-1213). The signals that attract lymphocytes and monocytes into the aortic wall in aneurysmal disease remain to be precisely defined. We have studied the production of the chemotactic cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by aortic tissues obtained from 47 subjects. We compared the antigenic production of these cytokines by explants of: 1) human abdominal aneurysmal tissue, 2) occlusive (atherosclerotic) aortas, and 3) normal aortas. IL-8, which is chemotactic for neutrophils, lymphocytes, and endothelial cells was liberated in greater quantities by abdominal aortic aneurysms than by occlusive or normal aortas. Using immunohistochemistry, macrophages, and to a lesser degree endothelial cells, were found to be positive for the expression of antigenic IL-8. Similarly, MCP-1, a potent chemotactic cytokine for monocytes/macrophages, was released by explants from abdominal aortic aneurysms in greater quantities than by explants from occlusive or normal aortas. Using immunohistochemistry, the predominant MCP-1 antigen-positive cells were macrophages and to a lesser extent smooth muscle cells. Our results indicate that human abdominal aortic aneurysms produce IL-8 and MCP-1, both of which may serve to recruit additional inflammatory cells into the abdominal aortic wall, hence perpetuating the inflammatory reaction that may result in the pathology of vessel wall destruction and aortic aneurysm formation. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8494046

  15. Talk to Your Doctor about Abdominal Aortic Aneurysm

    MedlinePlus

    ... español Talk to Your Doctor about Abdominal Aortic Aneurysm Browse Sections The Basics Overview What is AAA? ... doctor about getting screened (tested) for abdominal aortic aneurysm (AAA). If AAA isn't found and treated ...

  16. Genetics Home Reference: familial thoracic aortic aneurysm and dissection

    MedlinePlus

    ... Home Health Conditions familial TAAD familial thoracic aortic aneurysm and dissection Enable Javascript to view the expand/ ... Open All Close All Description Familial thoracic aortic aneurysm and dissection ( familial TAAD ) involves problems with the ...

  17. Ventricular tachycardia following trans-apical aortic valve replacement.

    PubMed

    Beinart, Roy; Danik, Stephan; Palacios, Igor; Barrett, Conor; Inglessis, Ignacio; Agnihotri, Arvind; Passeri, Jonathan

    2012-03-01

    Transcatheter aortic valve replacement (TAVR) is a relatively new procedure for high-risk patients with severe aortic stenosis. We report a case of a new left ventricular outflow tract ventricular tachycardia following TAVR. PMID:22016303

  18. Real-time imaging required for optimal echocardiographic assessment of aortic valve calcification

    PubMed Central

    Yousry, Mohamed; Rickenlund, Anette; Petrini, Johan; Gustavsson, Tomas; Prahl, Ulrica; Liska, Jan; Eriksson, Per; Franco-Cereceda, Anders; Eriksson, Maria J; Caidahl, Kenneth

    2012-01-01

    Introduction Aortic valve calcification (AVC), even without haemodynamic significance, may be prognostically import as an expression of generalized atherosclerosis, but techniques for echocardiographic assessment are essentially unexplored. Methods Two-dimensional (2D) echocardiographic recordings (Philips IE33) of the aortic valve in short-axis and long-axis views were performed in 185 consecutive patients within 1 week before surgery for aortic stenosis (n = 109, AS), aortic regurgitation (n = 61, AR), their combination (n = 8) or dilation of the ascending aorta (n = 7). The grey scale mean (GSMn) of the aortic valve in an end-diastolic short-axis still frame was measured. The same frame was scored visually 1–5 as indicating that the aortic valve was normal, thick, or had mild, moderate or severe calcification. The visual echodensity of each leaflet was determined real time applying the same 5-grade scoring system for each leaflet, and the average for the whole valve was calculated. Finally, a similar calcification score for the whole valve based on inspection and palpation by the surgeon was noted. Results Visual assessment of real-time images using the proposed scoring system showed better correlation with the surgical evaluation of the degree of valve calcification (r = 0·83, P<0·001) compared to evaluation of stop frames by visual assessment (r = 0·66, P<0·001) or the GSMn score (r = 0·64, P<0·001). High inter- and intra-observer correlations were observed for real-time visual score (both intraclass correlation coefficient = 0·93). Conclusion Real-time evaluation of the level of AVC is superior to using stop frames assessed either visually or by dedicated computer grey scale measurement software. PMID:23031068

  19. Neurological Complications Following Endoluminal Repair of Thoracic Aortic Disease

    SciTech Connect

    Morales, J. P.; Taylor, P. R.; Bell, R. E.; Chan, Y. C.; Sabharwal, T.; Carrell, T. W. G.; Reidy, J. F.

    2007-09-15

    Open surgery for thoracic aortic disease is associated with significant morbidity and the reported rates for paraplegia and stroke are 3%-19% and 6%-11%, respectively. Spinal cord ischemia and stroke have also been reported following endoluminal repair. This study reviews the incidence of paraplegia and stroke in a series of 186 patients treated with thoracic stent grafts. From July 1997 to September 2006, 186 patients (125 men) underwent endoluminal repair of thoracic aortic pathology. Mean age was 71 years (range, 17-90 years). One hundred twenty-eight patients were treated electively and 58 patients had urgent procedures. Anesthesia was epidural in 131, general in 50, and local in 5 patients. Seven patients developed paraplegia (3.8%; two urgent and five elective). All occurred in-hospital apart from one associated with severe hypotension after a myocardial infarction at 3 weeks. Four of these recovered with cerebrospinal fluid (CSF) drainage. One patient with paraplegia died and two had permanent neurological deficit. The rate of permanent paraplegia and death was 1.6%. There were seven strokes (3.8%; four urgent and three elective). Three patients made a complete recovery, one had permanent expressive dysphasia, and three died. The rate of permanent stroke and death was 2.1%. Endoluminal treatment of thoracic aortic disease is an attractive alternative to open surgery; however, there is still a risk of paraplegia and stroke. Permanent neurological deficits and death occurred in 3.7% of the patients in this series. We conclude that prompt recognition of paraplegia and immediate insertion of a CSF drain can be an effective way of recovering spinal cord function and improving the prognosis.

  20. Thoracic Endovascular Stent Graft Repair of Middle Aortic Syndrome.

    PubMed

    Kim, Joung Taek; Lee, Mina; Kim, Young Sam; Yoon, Yong Han; Baek, Wan Ki

    2016-09-01

    Middle aortic syndrome is a rare disease defined as a segmental narrowing of the distal descending thoracic or abdominal aorta. A thoracoabdominal bypass or endovascular treatment is the choice of treatment. Endovascular therapy consists of a balloon dilatation and stent implantation. Recently, thoracic endovascular aortic repair has been widely used in a variety of aortic diseases. We report a case of middle aortic syndrome treated with a thoracic endovascular stent graft. PMID:27549552

  1. Real-time transesophageal echocardiography facilitates antegrade balloon aortic valvuloplasty

    PubMed Central

    Ito, Kazato; Yano, Kentaro; Tanaka, Chiharu; Nakashoji, Tomohiro; Tonomura, Daisuke; Takehara, Kosuke; Kino, Naoto; Yoshida, Masataka; Kurotobi, Toshiya; Tsuchida, Takao; Fukumoto, Hitoshi

    2016-01-01

    We report two cases of severe aortic stenosis (AS) where antegrade balloon aortic valvuloplasty (BAV) was performed under real-time transesophageal echocardiography (TEE) guidance. Real-time TEE can provide useful information for evaluating the aortic valve response to valvuloplasty during the procedure. It was led with the intentional wire-bias technique in order to compress the severely calcified leaflet, and consequently allowed the balloon to reach the largest possible size and achieve full expansion of the aortic annulus. PMID:27054107

  2. Rapid prototyping in aortic surgery.

    PubMed

    Bangeas, Petros; Voulalas, Grigorios; Ktenidis, Kiriakos

    2016-04-01

    3D printing provides the sequential addition of material layers and, thus, the opportunity to print parts and components made of different materials with variable mechanical and physical properties. It helps us create 3D anatomical models for the better planning of surgical procedures when needed, since it can reveal any complex anatomical feature. Images of abdominal aortic aneurysms received by computed tomographic angiography were converted into 3D images using a Google SketchUp free software and saved in stereolithography format. Using a 3D printer (Makerbot), a model made of polylactic acid material (thermoplastic filament) was printed. A 3D model of an abdominal aorta aneurysm was created in 138 min, while the model was a precise copy of the aorta visualized in the computed tomographic images. The total cost (including the initial cost of the printer) reached 1303.00 euros. 3D imaging and modelling using different materials can be very useful in cases when anatomical difficulties are recognized through the computed tomographic images and a tactile approach is demanded preoperatively. In this way, major complications during abdominal aorta aneurysm management can be predicted and prevented. Furthermore, the model can be used as a mould; the development of new, more biocompatible, less antigenic and individualized can become a challenge in the future. PMID:26803324

  3. Flow in an Aortic Coarctation

    NASA Astrophysics Data System (ADS)

    Loma, Luis; Miller, Paul; Hertzberg, Jean

    2009-11-01

    Coarctation of the aorta is a congenital cardiovascular defect that causes a constriction in the descending thoracic aorta. To gain a better understanding of the cause of post-surgical problems, a rigid glass and a compliant in vitro model of the aortic arch and descending aorta with a coarctation were constructed. Near-physiologic compliance was obtained using a silicone elastomer. Stereoscopic PIV was used to obtain 3D velocity maps. Results show a high speed turbulent jet formed at the exit of the coarctation. Flow in the rigid model was significantly different from in the compliant model. In the rigid model, the jet was symmetric, creating a toroidal recirculation area. In the compliant model, the jet was directed towards the medial wall, inducing flow reversal only at the lateral wall. Peak velocities and turbulence intensities were higher in the rigid model, however shear rate values in the compliant model were significantly above both the rigid model and normal in vivo values at the medial wall. In both models the reattachment region fluctuated, creating oscillatory shear.

  4. Endovascular repair of abdominal aortic aneurysms.

    PubMed

    Arnaoutakis, Dean J; Zammert, Martin; Karthikesalingam, Alan; Belkin, Michael

    2016-09-01

    Endovascular repair of abdominal aortic aneurysms is an important technique in the vascular surgeon's armamentarium, which has created a seismic shift in the management of aortic pathology over the past two decades. In comparison to traditional open repair, the endovascular approach is associated with significantly improved perioperative morbidity and mortality. The early survival benefit of endovascular abdominal aortic aneurysm repair is sustained up to 3 years postoperatively, but longer-term life expectancy remains poor regardless of operative modality. Nonetheless, most abdominal aortic aneurysms are now repaired using endovascular stent grafts. The technology is not perfect as several postoperative complications, namely endoleak, stent-graft migration, and graft limb thrombosis, can develop and therefore lifelong imaging surveillance is required. In addition, a postoperative inflammatory response has been documented after endovascular repair of aortic aneurysms; the clinical significance of this finding has yet to be determined. Subsequently, the safety and applicability of endovascular stent grafts are likely to improve and expand with the introduction of newer-generation devices and with the simplification of fenestrated systems. PMID:27650343

  5. Primary Stenting in Infrarenal Aortic Occlusive Disease

    SciTech Connect

    Nyman, Ulf; Uher, Petr; Lindh, Mats; Lindblad, Bengt; Ivancev, Krasnodar

    2000-03-15

    Purpose: To evaluate the results of primary stenting in aortic occlusive disease.Methods: Thirty patients underwent primary stenting of focal concentric (n = 2) and complex aortic stenoses (n = 19), and aortic or aorto-iliac occlusions (n = 9). Sixteen patients underwent endovascular outflow procedures, three of whom also had distal open surgical reconstructions. Median follow-up was 16 months (range 1-60 months).Results: Guidewire crossing of two aorto-biiliac occlusions failed, resulting in a 93% (28/30) technical success. Major complications included one access hematoma, one myocardial infarction, one death (recurrent thromboembolism) in a patient with widespread malignancy, and one fatal hemorrhage during thrombolysis of distal emboli from a recanalized occluded iliac artery. One patient did not improve his symptoms, resulting in a 1-month clinical success of 83% (25/30). Following restenting the 26 stented survivors changed their clinical limb status to +3 (n = 17) and +2 (n = 9). During follow-up one symptomatic aortic restenosis occurred and was successfully restented.Conclusions: Primary stenting of complex aortic stenoses and short occlusions is an attractive alternative to conventional surgery. Larger studies with longer follow-up and stratification of lesion morphology are warranted to define its role relative to balloon angioplasty. Stenting of aorto-biiliac occlusions is feasible but its role relative to bypass grafting remains to be defined.

  6. Echocardiographic assessment of severity of aortic regurgitation.

    PubMed Central

    Gray, K E; Barritt, D W

    1975-01-01

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

  7. Advances in Transcatheter Aortic Valve Replacement

    PubMed Central

    Kleiman, Neal S.; Reardon, Michael J.

    2016-01-01

    Transcatheter aortic valve replacement (TAVR) is becoming widely used for the treatment of symptomatic severe aortic stenosis in patients with high surgical risk. Data from The PARTNER Trial (Placement of AoRtic TraNscathetER Valves) and the Medtronic CoreValve® U.S. Pivotal Investigational Device Exemption trial indicate that survival for extreme-risk patients is superior to best medical therapy and equivalent or superior to surgical aortic valve replacement (SAVR), although long-term durability remains unknown. Paravalvular leak remains higher in TAVR than SAVR, as does permanent pacemaker implantation in self-expanding valves. New-generation valves are addressing these issues, especially for paravalvular leak. There is strong evidence that TAVR is appropriate for both extreme-risk and high-risk patients with symptomatic severe aortic stenosis, and the continued development of new valves are making implantation more reliable. This review discusses the studies supporting the use of TAVR and explores current advances in the field. PMID:27127560

  8. Endovascular repair of a type B aortic dissection with a right-sided aortic arch: case report

    PubMed Central

    2013-01-01

    Right-sided aortic arch is a rare anomaly, and aortic dissection involving a right-sided aortic arch is extremely rare. We report the case of a 65-year-old man with a right-sided aortic arch and a right descending aortic dissection and a stent-graft was accurately deployed without perioperative complications. There were no any complaints and complications after 18 months follow-up. The CTA demonstrated that the false lumen was largely thrombosed only with a mild type II endoleak and a mild descending aortic expansion. We feel that endovascular repair is feasible to patient of type B aortic dissection with a right-sided aortic arch. However, long-term clinical efficacy and safety have yet to be confirmed. PMID:23343010

  9. Late degeneration of transcatheter aortic valves: pathogenesis and management.

    PubMed

    Barbanti, Marco; Tamburino, Corrado

    2016-09-18

    There is a growing body of evidence demonstrating the durability of current transcatheter aortic valve implantation (TAVI) devices up to 5 years. However, it is well known that transcatheter aortic valves can degenerate in a manner similar to surgical bioprostheses. In this review we briefly discuss the modes of failure of trans-catheter aortic valves and their potential management. PMID:27640028

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

    PubMed

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

    2000-04-01

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

  11. Diagnosis and management of acute aortic syndromes: dissection, intramural hematoma, and penetrating aortic ulcer.

    PubMed

    Bonaca, Marc P; O'Gara, Patrick T

    2014-01-01

    Acute aortic syndromes constitute a spectrum of conditions characterized by disruptions in the integrity of the aortic wall that may lead to potentially catastrophic outcomes. They include classic aortic dissection, intramural hematoma, and penetrating aortic ulcer. Although imaging studies are sensitive and specific, timely diagnosis can be delayed because of variability in presenting symptoms and the relatively low frequency with which acute aortic syndromes are seen in the emergency setting. Traditional classification systems, such as the Stanford system, facilitate early treatment decision-making through recognition of the high risk of death and major complications associated with involvement of the ascending aorta (type A). These patients are treated surgically unless intractable and severe co-morbidities are present. Outcomes with dissections that do not involve the ascending aorta (type B) depend on the presence of acute complications (e.g., malperfusion, early aneurysm formation, leakage), the patency and size of the false lumen, and patient co-morbidities. Patients with uncomplicated type B dissections are initially treated medically. Endovascular techniques have emerged as an alternative to surgery for the management of complicated type B dissections when intervention is necessary. Patients with acute aortic syndromes require aggressive medical care, risk stratification for additional complications and targeted genetic assessment as well as careful long-term monitoring to assess for evolving complications. The optimal care of patients with acute aortic syndrome requires the cooperation of members of an experienced multidisciplinary team both in the acute and chronic setting.

  12. mRNA expressions of inducible nitric oxide synthase, endothelial nitric oxide synthase, and neuronal nitric oxide synthase genes in meningitis patients.

    PubMed

    Oztuzcu, Serdar; Igci, Yusuf Ziya; Arslan, Ahmet; Sivasli, Ercan; Ozkara, Esma; Igci, Mehri; Demiryürek, Seniz; Cengiz, Beyhan; Gogebakan, Bulent; Namiduru, Mustafa; Coskun, Mehmet Yavuz; Cakmak, Ecir Ali

    2011-03-01

    Meningitis is an inflammation of the protective membranes covering the brain and spinal cord caused by bacteria, fungi, or viruses with various clinical symptoms. Although meningitis is not so prevalent, it remains the most serious contagious disease. The aim of our study was to investigate the effect of gene expressions of nitric oxide synthases (NOS) on meningitis patients. Using samples taken from 61 meningitis patients, inducible NOS, endothelial NOS (eNOS), and neuronal NOS mRNA levels were assessed in both blood and cerebrospinal fluid (CSF). A control group was constructed of 64 healthy persons. The gene expression analysis was made using real-time polymerase chain reaction method. There was no neuronal NOS expression in either group, whereas inducible NOS expression was detected in 40 blood samples and 12 CSF samples from meningitis patients. However, there were no marked differences between groups (p=0.5104). eNOS expression was detected in all blood and CSF samples, which was markedly higher in patients (p=0.0367). Because the increase in eNOS expression increases NO production, eNOS expression in meningitis patients is of great importance. This increase of eNOS in meningitis patients compared with healthy subjects may lead to novel treatments for reducing the severity of the disease.

  13. 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

  14. Diagnosis and Management of Valvular Aortic Stenosis

    PubMed Central

    Czarny, Matthew J; Resar, Jon R

    2014-01-01

    Valvular aortic stenosis (AS) is a progressive disease that affects 2% of the population aged 65 years or older. The major cause of valvular AS in adults is calcification and fibrosis of a previously normal tricuspid valve or a congenital bicuspid valve, with rheumatic AS being rare in the United States. Once established, the rate of progression of valvular AS is quite variable and impossible to predict for any particular patient. Symptoms of AS are generally insidious at onset, though development of any of the three cardinal symptoms of angina, syncope, or heart failure portends a poor prognosis. Management of symptomatic AS remains primarily surgical, though transcatheter aortic valve replacement (TAVR) is becoming an accepted alternative to surgical aortic valve replacement (SAVR) for patients at high or prohibitive operative risk. PMID:25368539

  15. Aortic stiffness and distensibility among hypertensives.

    PubMed

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

    2009-09-01

    Hypertension is one among many factors that contribute to aortic stiffness, which has repercussions mainly on the heart. To assess aortic stiffness among essential hypertensives of South India and its relationship with gender. An analytical study was designed to assess aortic stiffness among 60 nonobese, nonalcoholic, nonsmoking, and non-caffeine consuming essential hypertensives without any overt illness or infection, and compared with 30 healthy age- and sex-matched nonhypertensives. They were assessed clinically and also by laboratory means. Their left ventricular mass (LV) and left ventricular ejection fraction (LVEF) were measured using Transthoracic echocardiogram. Aortic systolic and diastolic diameters were measured by using M-mode echocardiography during consecutive beats and averaged for each case. Finally, aortic stiffness was calculated. The data were analyzed statistically. Hypertensives were divided into Group I, consisting of patients with hypertension at least for 5 years, who were not adherent to medication, and Group II, consisting of patients with hypertension of duration between 6 months and 1 year. There were 20 males and 10 females in each group. There was no significant difference between the hypertensive groups and a control, normotensive, group with regard to BMI or total cholesterol. The means of LV mass (in grams), systolic BP (in mmHg), diastolic BP (in mmHg), aortic systolic diameter (in mm), aortic diastolic diameter (in mm), aortic distensibility (in mm), and aortic stiffness found in Group I, Group II, and controls were 105.8 +/- 23.8, 101.5 +/- 21, and 84 +/- 9.8; 138 +/- 14.2, 153 +/- 17.1, and 120 +/- 8.3; 90.5 +/- 11.6, 101.7 +/- 17.1, and 76.5 +/- 5; 30.85 +/- 2.6, 28.7 +/- 2.6, and 27.7 +/- 2.4; 28.7 +/- 2.2, 25.8 +/- 2.5, and 24.2 +/- 2.5; 2.14 +/- 0.3, 2.84 +/- 0.5, and 3.5 +/- 0.6; and 1.31 +/- 0.09, 1.14 +/- 0.1, and 1.04 +/- 0.08, respectively. The differences between the hypertensive groups and the control group were

  16. ED 02-1 ACUTE AORTIC SYNDROME.

    PubMed

    Song, Jae-Kwan

    2016-09-01

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

  17. Mechanical versus biological aortic valve replacement strategies.

    PubMed

    Reineke, D; Gisler, F; Englberger, L; Carrel, T

    2016-01-01

    Aortic valve replacement (AVR) is the most frequently performed procedure in valve surgery. The controversy about the optimal choice of the prosthetic valve is as old as the technique itself. Currently there is no perfect valve substitute available. The main challenge is to choose between mechanical and biological prosthetic valves. Biological valves include pericardial (bovine, porcine or equine) and native porcine bioprostheses designed in stented, stentless and sutureless versions. Homografts and pulmonary autografts are reserved for special indications and will not be discussed in detail in this review. We will focus on the decision making between artificial biological and mechanical prostheses, respectively. The first part of this article reviews guideline recommendations concerning the choice of aortic prostheses in different clinical situations while the second part is focused on novel strategies in the treatment of patients with aortic valve pathology. PMID:26678683

  18. Temporary extracorporeal bypass modalities during aortic surgery.

    PubMed

    Bassin, Levi; Bell, David

    2016-09-01

    The key to aortic surgery is protection of the brain, heart, spinal cord, and viscera. For operations involving the aortic arch, the focus is on cerebral protection, while for pathology involving the descending thoracic aorta, the focus is on spinal protection. Optimal cerebral and spinal protection requires an extensive knowledge of the operative steps and an understanding of the cardiopulmonary bypass modalities that are possible. A bloodless field is required when operating on the aorta. As a result, periods of ischemia to the central nervous system and end-organ viscera are often unavoidable. The main techniques to mitigate ischemia include hypothermia and selective perfusion of the ischemic organ in question. This chapter will first briefly review bypass modalities and then describe how they can be used for various aortic scenarios. PMID:27650344

  19. Endovascular repair of thoracic aortic aneurysm

    PubMed Central

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

    2010-01-01

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

  20. Prostaglandin receptor EP4 in abdominal aortic aneurysms.

    PubMed

    Cao, Richard Y; St Amand, Tim; Li, XinZhi; Yoon, Sung-Hee; Wang, Carol P; Song, Hui; Maruyama, Takayuki; Brown, Peter M; Zelt, David T; Funk, Colin D

    2012-07-01

    Abdominal aortic aneurysm (AAA) pathogenesis is distinguished by vessel wall inflammation. Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1, key components of the most well-characterized inflammatory prostaglandin pathway, contribute to AAA development in the 28-day angiotensin II infusion model in mice. In this study, we used this model to examine the role of the prostaglandin E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%) in AAA pathogenesis. The administration of the prostaglandin receptor EP4 antagonist AE3-208 (10 mg/kg per day) to apolipoprotein E (apoE)-deficient mice led to active drug plasma concentrations and reduced AAA incidence and severity compared with control apoE-deficient mice (P < 0.01), whereas COX-2 genetic knockdown/apoE-deficient mice displayed only a minor, nonsignificant decrease in incidence of AAA. EP4 receptor protein was present in human and mouse AAA, as observed by using Western blot analysis. Aortas from AE3-208-treated mice displayed evidence of a reduced inflammatory phenotype compared with controls. Atherosclerotic lesion size at the aortic root was similar between all groups. In conclusion, the prostaglandin E(2)-EP4 signaling pathway plays a role in the AAA inflammatory process. Blocking the EP4 receptor pharmacologically reduces both the incidence and severity of AAA in the angiotensin II mouse model, potentially via attenuation of cytokine/chemokine synthesis and the reduction of matrix metalloproteinase activities.

  1. Distinctive expression patterns of hypoxia-inducible factor-1α and endothelial nitric oxide synthase following hypergravity exposure

    PubMed Central

    Yoon, Gun; Oh, Choong Sik; Kim, Hyun-Soo

    2016-01-01

    This study was designed to examine the expression of hypoxia-inducible factor-1α (HIF-1α) and the level and activity of endothelial nitric oxide synthase (eNOS) in the hearts and livers of mice exposed to hypergravity. Hypergravity-induced hypoxia and the subsequent post-exposure reoxygenation significantly increased cardiac HIF-1α levels. Furthermore, the levels and activity of cardiac eNOS also showed significant increase immediately following hypergravity exposure and during the reoxygenation period. In contrast, the expression of phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) showed significant elevation only during the reoxygenation period. These data raise the possibility that the increase in cardiac HIF-1α expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1α expression was significantly increased immediately after hypergravity exposure, indicating that hypergravity exposure to causes hepatocellular hypoxia. The hypergravity-exposed livers showed significantly higher eNOS immunoreactivity than did those of control mice. Consistent with these results, significant increases in eNOS activity and nitrate/nitrite levels were also observed. These findings suggest that hypergravity-induced hypoxia plays a significant role in the upregulation of hepatic eNOS. PMID:27191892

  2. Spinal ischemia following abdominal aortic surgery.

    PubMed

    Ferguson, L R; Bergan, J J; Conn, J; Yao, J S

    1975-03-01

    Serious spinal cord ischemia may follow infrarenal abdominal aortic surgery. Five cases are summarized and added to the 23 previously published cases in order to identify this syndrome, emphasize its importance, and draw attention to the possibility of spontaneous recovery which may occur. The multifactorial complex which comprises each patient's clinical picture clouds a precise and specific cause for paraplegia in these cases. However, neither hypotension, steal phenomena nor emboli are necessary for completion of the syndrome. The relevant spinal cord arterial anatomy indicates that the common anomalies which occur favor development of spinal cord ischemia in the arteriosclerotic population which requires aortic surgery. No means of prevention is possible at this time.

  3. Idiopathic thoracic aortic aneurysm at pediatric age.

    PubMed

    Marín-Manzano, E; González-de-Olano, D; Haurie-Girelli, J; Herráiz-Sarachaga, J I; Bermúdez-Cañete, R; Tamariz-Martel, A; Cuesta-Gimeno, C; Pérez-de-León, J

    2009-03-01

    A 6-year-old-boy presented with epigastric pain and vomiting over 1 year. Chest X-ray and esophagogastric transit showed a mediastinal mass. A chest computerized tomography angiogram demonstrated a descending thoracic aortic aneurysm. Analytical determinations carried out were all negative. The aneurysm was surgically repaired using a Dacron patch. The anatomopathological study described atherosclerotic lesions with calcifications, compatible with an atherosclerotic aneurysm wall. Aneurysms are uncommon in the pediatric population. Usually, no pathogenesis can be determined, and thus, such cases are grouped as idiopathic. Direct repair with or without patch is a therapeutic alternative in pediatric aneurysms and can allow the growth of the aortic circumference.

  4. Contemporary management of blunt aortic trauma.

    PubMed

    Dubose, J J; Azizzadeh, A; Estrera, A L; Safi, H J

    2015-10-01

    Blunt thoracic aortic injury (BTAI) remains a common cause of death following blunt mechanisms of trauma. Among patients who survive to reach hospital care, significant advances in diagnosis and treatment afford previously unattainable survival. The Society for Vascular Surgery (SVS) guidelines provide current best-evidence suggestions for treatment of BTAI. However, several key areas of controversy regarding optimal BTAI care remain. These include the refinement of selection criteria, timing for treatment and the need for long-term follow-up data. In addition, the advent of the Aortic Trauma Foundation (ATF) represents an important development in collaborative research in this field.

  5. 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

  6. 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

  7. Pleural Empyema and Aortic Aneurysm

    PubMed Central

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

    2015-01-01

    Abstract Pleural empyema (PE) may evolve into necrosis, fistula in the thorax, and sepsis; thus, it is also associated with high mortality. We investigated and analyzed the risk of aortic aneurysm (AA) in a cohort study of patients with PE. A total of 34,250 patients diagnosed with PE were identified as the PE cohort, and 137,000 patients without PE were selected randomly as the control group and matched by sex, age, and index year of PE diagnosis. Patients ages 20 years and younger with a history of AA were excluded. The risk of AA was analyzed using a Cox proportional hazards regression model. Excess risk of AA development was 1.69-fold higher in PE patients (adjusted hazard ratio [aHR] = 1.69; 95% confidence interval [CI] = 1.39–2.05) compared with non-PE patients. The patients with PE exhibited a greater adjusted risk of AA (aHR = 2.01; CI = 1.44–2.81) even if they did not have any of the 9 comorbidities included in our analysis (diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, heart failure, cardiac artery disease, stroke, bacterial endocarditis, and rheumatic endocarditis). Compared with the patients without any of the 9 comorbidities or PE, the patients with only PE had a greater risk of developing AA (aHR = 2.00; CI = 1.43–2.79). The PE cohort had a significantly higher cumulative incidence of AA than the non-PE cohort did during 12 years of follow-up. In a large-scale cohort, patients with PE are linked with an increased risk of AA. PMID:26632741

  8. Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kandasamy, Kannan; Choudhury, Soumen; Kutty, Harikumar Sankaran; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2015-07-25

    The groundwater pollutant arsenic can cause various cardiovascular disorders. Angiotensin II, a potent vasoconstrictor, plays an important role in vascular dysfunction by promoting changes in endothelial function, vascular reactivity, tissue remodeling and oxidative stress. We investigated whether modulation of angiotensin II signaling and redox homeostasis could be a mechanism contributing to arsenic-induced vascular disorder. Rats were exposed to arsenic at 25, 50 and 100ppm of sodium arsenite through drinking water consecutively for 90 days. Blood pressure was recorded weekly. On the 91st day, the rats were sacrificed for blood collection and isolation of thoracic aorta. Angiotensin converting enzyme and angiotensin II levels were assessed in plasma. Aortic reactivity to angiotensin II was assessed in organ-bath system. Western blot of AT1 receptors and G protein (Gαq/11), ELISA of signal transducers of MAP kinase pathway and reactive oxygen species (ROS) generation were assessed in aorta. Arsenic caused concentration-dependent increase in systolic, diastolic and mean arterial blood pressure from the 10th, 8th and 7th week onwards, respectively. Arsenic caused concentration-dependent enhancement of the angiotensin II-induced aortic contractile response. Arsenic also caused concentration-dependent increase in the plasma levels of angiotensin II and angiotensin converting enzyme and the expression of aortic AT1 receptor and Gαq/11 proteins. Arsenic increased aortic protein kinase C activity and the concentrations of protein tyrosine kinase, extracellular signal-regulated kinase-1/2 and vascular endothelial growth factor. Further, arsenic increased aortic mRNA expression of Nox2, Nox4 and p22phox, NADPH oxidase activity and ROS generation. The results suggest that arsenic-mediated enhancement of angiotensin II signaling could be an important mechanism in the arsenic-induced vascular disorder, where ROS could augment the angiotensin II signaling through activation

  9. Infected abdominal aortic aneurysm due to Morganella morganii: CT findings.

    PubMed

    Kwon, Oh Young; Lee, Jong Seok; Choi, Han Sung; Hong, Hoon Pyo; Ko, Young Gwan

    2011-02-01

    An infected aortic aneurysm, or mycotic aneurysm, is a rare arterial dilatation due to destruction of the infected vessel wall. Common pathogens resulting in an infected aortic aneurysm are Salmonella and Clostridium species, as well as Staphylococcus aureus; Morganella morganii, on the other hand, is very rare. An infected abdominal aortic aneurysm has tendencies to grow rapidly and to rupture. The mortality rate is high in patients undergoing emergent surgical intervention. We report the case of a 65-year-old man who presented with an infected abdominal aortic aneurysm caused by M. morganii. A high index of suspicion and imaging tests are necessary in order to diagnose an infected aortic aneurysm.

  10. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.

    PubMed

    Carrion, Katrina; Dyo, Jeffrey; Patel, Vishal; Sasik, Roman; Mohamed, Salah A; Hardiman, Gary; Nigam, Vishal

    2014-01-01

    Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1-2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-catenin is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-catenin signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification. PMID:24788418

  11. Expression analysis of NOS family and HSP genes during thermal stress in goat ( Capra hircus)

    NASA Astrophysics Data System (ADS)

    Yadav, Vijay Pratap; Dangi, Satyaveer Singh; Chouhan, Vikrant Singh; Gupta, Mahesh; Dangi, Saroj K.; Singh, Gyanendra; Maurya, Vijay Prakash; Kumar, Puneet; Sarkar, Mihir

    2016-03-01

    Approximately 50 genes other than heat shock protein (HSP) expression changes during thermal stress. These genes like nitric oxide synthase (NOS) need proper attention and investigation to find out their possible role in the adaptation to thermal stress in animals. So, the present study was undertaken to demonstrate the expressions of inducible form type II NOS (iNOS), endothelial type III NOS (eNOS), constitutively expressed enzyme NOS (cNOS), HSP70, and HSP90 in peripheral blood mononuclear cells (PBMCs) during different seasons in Barbari goats. Real-time polymerase chain reaction, western blot, and immunocytochemistry were applied to investigate messenger RNA (mRNA) expression, protein expression, and immunolocalization of examined factors. The mRNA and protein expressions of iNOS, eNOS, cNOS, HSP70, and HSP90 were significantly higher ( P < 0.05) during peak summer, and iNOS and eNOS expressions were also observed to be significantly higher ( P < 0.05) during peak winter season as compared with moderate season. The iNOS, eNOS, cNOS, HSP70, and HSP90 were mainly localized in plasma membrane and cytoplasm of PBMCs. To conclude, data generated in the present study indicate the possible involvement of the NOS family genes in amelioration of thermal stress so as to maintain cellular integrity and homeostasis in goats.

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

    PubMed

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

    2015-03-01

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

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

    SciTech Connect

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

    2008-07-15

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

  14. The Triplex BioValsalva Prostheses To Reconstruct the Aortic Valve and the Aortic Root.

    PubMed

    Fu, Yijun; Li, Bin; Bourget, Jean-Michel; Bondarenko, Olexandr; Lin, Jing; Guzman, Randolph; Paynter, Royston; Desaulniers, Denis; Qin, Boyin; Wang, Lu; Germain, Lucie; Zhang, Ze; Guidoin, Robert

    2016-01-01

    The Bentall procedure introduced in 1968 represents an undisputed cure to treat multiple pathologies involving the aortic valve and the ascending thoracic aorta. Over the years, multiple modifications have been introduced as well as a standardized approach to the operation with the goal to prevent long-term adverse events. The BioValsalva prosthesis provides a novel manner to more efficiently reconstruct the aortic valve together with the anatomy of the aortic root with the implantation of a valved conduit. This prosthesis comprises three sections: the collar supporting the valve; the skirt mimicking the Valsalva, which is suitable for the anastomoses with the coronary arteries; and the main body of the graft, which is designed to replace the ascending aorta. The BioValsalva prosthesis allows the Bentall operation to be used in patients whose aortic valve cannot be spared. PMID:27649763

  15. Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

    PubMed Central

    Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

    2016-01-01

    Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

  16. Aortic dilatation and aortopathy in congenital heart diseases.

    PubMed

    Zanjani, Keyhan Sayadpour; Niwa, Koichiro

    2013-01-01

    Longer survival after corrective surgery for congenital heart diseases has rendered late complications more important. One of these complications is aortic dilatation which may occur in patients with repaired or unrepaired disease and can progress to aneurysm, dissection, and rupture. This aortic dilatation in various congenital heart diseases does not simply mean anatomical dilatation of the aortic root, but it closely relates to the aortic pathophysiological abnormality, aortic regurgitation, and aortic and ventricular dysfunction; therefore, we can recognize this complex lesion as a new concept: "aortopathy". The pathophysiology of this disease is complex and only partially understood. In this review, we first discuss history, pathophysiology, and clinical features of aortic dilatation and aortopathy of congenital heart disease. Then we provide a review of the evaluation and management of this disease.

  17. Aortic valve-sparing in aortic dissection with transposition of great arteries.

    PubMed

    Sharma, Rajiv; Cohen, Brent; Peters, Paul; Shah, Pallav

    2013-04-01

    Patients with transposition of the great arteries have good survival after surgery, but some have complications ranging from heart failure to valve dysfunction. A 42-year-old woman who underwent surgical correction in childhood, presented with aortic dissection and had a valve-sparing root operation, but died immediately postoperatively. Both aortic dissection and valve-sparing root operations in this setting have not been described before. This case highlights facts to consider in the treatment of this presentation. PMID:24532622

  18. 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

  19. 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.

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

    PubMed Central

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

    2016-01-01

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

  1. 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

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

    PubMed

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

    2013-01-01

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

  3. 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

  4. Ultrasonic delineation of aortic microstructure: The relative contribution of elastin and collagen to aortic elasticity

    NASA Astrophysics Data System (ADS)

    Marsh, Jon N.; Takiuchi, Shin; Lin, Shiow Jiuan; Lanza, Gregory M.; Wickline, Samuel A.

    2004-05-01

    Aortic elasticity is an important factor in hemodynamic health, and compromised aortic compliance affects not only arterial dynamics but also myocardial function. A variety of pathologic processes (e.g., diabetes, Marfan's syndrome, hypertension) can affect aortic elasticity by altering the microstructure and composition of the elastin and collagen fiber networks within the tunica media. Ultrasound tissue characterization techniques can be used to obtain direct measurements of the stiffness coefficients of aorta by measurement of the speed of sound in specific directions. In this study we sought to define the contributions of elastin and collagen to the mechanical properties of aortic media by measuring the magnitude and directional dependence of the speed of sound before and after selective isolation of either the collagen or elastin fiber matrix. Formalin-fixed porcine aortas were sectioned for insonification in the circumferential, longitudinal, or radial direction and examined using high-frequency (50 MHz) ultrasound microscopy. Isolation of the collagen or elastin fiber matrices was accomplished through treatment with NaOH or formic acid, respectively. The results suggest that elastin is the primary contributor to aortic medial stiffness in the unloaded state, and that there is relatively little anisotropy in the speed of sound or stiffness in the aortic wall.

  5. Linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, stimulate c-Fos, c-Jun, and c-Myc mRNA expression, mitogen-activated protein kinase activation, and growth in rat aortic smooth muscle cells.

    PubMed Centra