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  1. The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells.

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    Halliday, F. C.; Aaronson, P. I.; Evans, A. M.; Gurney, A M

    1995-01-01

    1. Using the whole-cell patch-clamp technique, the effects of several K+ channel blocking drugs on K+ current recorded from rabbit isolated aortic smooth muscle cells were investigated. 2. Upon depolarization from -80 mV, outward K+ current composed of several distinct components were observed: a transient, 4-aminopyridine (4-AP)-sensitive component (I1) and a sustained component (Isus), comprising a 4-AP-sensitive delayed rectifier current (IK(V)), and a noisy current which was sensitive to ...

  2. Alterations in alpha sub 1 - adrenoceptor function in rabbit aortic smooth muscle after long term administration of verapamil

    Energy Technology Data Exchange (ETDEWEB)

    Aceto, J.F.

    1988-01-01

    Aortic rings from naive rabbits and rabbits previously treated with large doses of verapamil for eight days were studied in vitro on day nine. Treated rings showed a decrease in norepinephrine potency and maximum developed isometric tension. Standard tissue bath analysis revealed a significant increase in the apparent dissociation constant of norepinephrine for the adrenoceptor which partly accounts for the decreased potency. Similar changes in potency and efficacy were found with other selected vasoconstrictors namely angiotensin, serotonin, and KCl. In contrast to the affinity change for norepinephrine, the alpha-adrenoceptor specific antagonist phentolamine revealed no change in adrenoceptor affinity after verapamil pretreatment. Further investigation using direct binding with {sup 125}I-labelled BE 2254, a high affinity alpha-adrenoceptor antagonist, showed only a slight decrease in the affinity of the pretreated tissues studied, thereby confirming that the main effect of chronic verapamil is peculiar to agonists.

  3. Relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium induced by new nitric oxide donor substances of the nitrosyl-ruthenium complex

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    Joao B. G. Cerqueira

    2008-10-01

    Full Text Available INTRODUCTION: Endothelial dysfunction characterized by endogenous nitric oxide (NO deficiency made 56% of patients affected with erectile dysfunction decline treatment with PDE-5 inhibitors. New forms of treatment are currently being developed for this group of patients. MATERIALS AND METHODS: The study compared the effect of sodium nitroprusside (SNP and two substances of the nitrosyl-ruthenium complex, cis-[Ru(bpy2(SO3(NO]PF-6-9 ("FONO1” and trans-[Ru(NH34(caffeine(NO]C13 ("LLNO1” on relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium. The samples were immersed in isolated baths and precontracted with 0.1 µM phenylephrine (PE and the corresponding relaxation concentration/response curves were plotted. In order to investigate the relaxation mechanisms involved, 100 µM ODQ (a soluble guanylate cyclase-specific inhibitor, 3 µM or 10 µM oxyhemoglobin (an extracellular NO scavenger or 1 mM L-cysteine (a nitrosyl anion-specific scavenger was added to the samples. RESULTS: All the NO donors tested produced a significant level of relaxation in the vascular endothelium. In corpus cavernosum samples, FONO1 produced no significant effect, but LLNO1 and SNP induced dose-dependent relaxation with comparable potency (pEC50 = 6.14 ± 0.08 and 6.4 ± 0.14, respectively and maximum effect (Emax = 82% vs. 100%, respectively. All NO donors were found to activate soluble guanylate cyclase, since the addition of the corresponding inhibitor (100 µM ODQ completely neutralized the relaxation effect observed. The addition of oxyhemoglobin reduced the relaxation effect, but did not inhibit it completely. In aortic vascular endothelium 3 µM oxyhemoglobin decreased the relaxation effect by 26% on the average, while 10 µM oxyhemoglobin reduced it by over 52%. The addition of 100 µM L-cysteine produced no significant inhibiting effect. CONCLUSIONS: These results suggest that LLNO1 and FONO1 are potent vasodilators. LLNO1 was

  4. Altered catecholamine receptor affinity in rabbit aortic intimal hyperplasia

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    O' Malley, M.K.; Cotecchia, S.; Hagen, P.O. (Duke University Medical Center, Durham, NC (USA))

    1991-08-01

    Intimal thickening is a universal response to endothelial denudation and is also thought to be a precursor of atherosclerosis. The authors have demonstrated selective supersensitivity in arterial intimal hyperplasia to norepinephrine and they now report a possible mechanism for this. Binding studies in rabbit aorta with the selective alpha 1-adrenergic radioligand 125I-HEAT demonstrated that there was no change in receptor density (20 {plus minus} 4 fmole/10(6) cells) in intact vascular smooth muscle cells at either 5 or 14 days after denudation. However, competition studies showed a 2.6-fold increase in alpha 1-adrenergic receptor affinity for norepinephrine in intimal hyperplastic tissue (P less than 0.05). This increased affinity for norepinephrine was associated with a greater increase in 32P-labeled phosphatidylinositol (148% intimal thickening versus 76% control) and phosphatidic acid (151% intimal thickening versus 56% control) following norepinephrine stimulation of free floating rings of intimal hyperplastic aorta. These data suggest that the catecholamine supersensitivity in rabbit aortic intimal hyperplasia is receptor mediated and may be linked to the phosphatidylinositol cycle.

  5. Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation.

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    Maiellaro-Rafferty, Kathryn; Weiss, Daiana; Joseph, Giji; Wan, William; Gleason, Rudolph L; Taylor, W Robert

    2011-08-01

    The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE(-/-)) mice that overexpress catalase in vascular smooth muscle cells (apoE(-/-)xTg(SMC-Cat)). At baseline, aortas from apoE(-/-)xTg(SMC-Cat) exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE(-/-) mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE(-/-)xTg(SMC-Cat) after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H(2)O(2) is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.

  6. Uremia modulates the phenotype of aortic smooth muscle cells

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    Madsen, Marie; Pedersen, Annemarie Aarup; Albinsson, Sebastian

    2017-01-01

    of moderate uremia in ApoE(-/-) mice increased atherosclerosis in the aortic arch en face 1.6 fold (p = 0.04) and induced systemic inflammation. Based on histological analyses of aortic root sections, uremia increased the medial area, while there was no difference in the content of elastic fibers or collagen...

  7. The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis

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    Alhomida AS

    2010-03-01

    Full Text Available Abstract Background The most important function of collagen and elastin is to induce several mechanical parameters which are known to play a dominant role in governing mechanical properties of the blood vessels. The aortic tissue of rabbit is one of the important sources of collagen and elastin. The effects of high fat diet (HFD on the hydroxyproline (Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits have not been documented before. The present study was undertaken to investigate the changes in Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits during the progression of atherosclerosis. The atherosclerotic model used in this study was the New Zealand white rabbit (male; 12 weeks old. Twenty five rabbits were individually caged, and divided into control group (NOR; n = 10 and HFD group (CHO; n = 15. The control group was fed (100 g/day of normal (NOR diet for a period of 15 weeks. The HFD group was fed normal diet supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day for the same period of time. Results We found that the TC, LDLC, and TG (mg/dl were significantly (p Conclusions These results suggest that percentage decrease in various Hyp fractions in aortic tissue of HFD rabbits are closely related to percentage decrease of collagen content in aortic tissues of HFD rabbits. These results also suggest that it may be possible to use the changes in various Hyp fractions in aortic tissues of rabbits as an important risk factor during the progression of atherosclerosis.

  8. The Origin of Neointimal Smooth Muscle Cells in Transplant Arteriosclerosis from Recipient Bone-marrow Cells in Rat Aortic Allograft

    Institute of Scientific and Technical Information of China (English)

    SONG Zifang; LI Wei; ZHENG Qichang; SHANG Dan; SHU Xiaogang; GUAN Siming

    2007-01-01

    In order to investigate the origin of neointimal smooth muscle cells in transplant arteriosclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wistar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohistochemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts.Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were significantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a distinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic allograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.

  9. Development of a novel rabbit model of abdominal aortic aneurysm via a combination of periaortic calcium chloride and elastase incubation.

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    Yonghua Bi

    Full Text Available BACKGROUND: The purpose of this study was to introduce a novel, simple and effective technique for creating a reliable rabbit model of abdominal aortic aneurysm (AAA via a combination of periaortic calcium chloride (CaCl2 and elastase incubation. METHODS: Forty-eight New Zealand white rabbits were divided into four groups. The AAA model was developed via a 20-minute periaortic incubation of CaCl2 (0.5 mol/L and elastase (1 Unit/µL in a 1.5-cm aortic segment (Group CE. A single incubation of CaCl2 (Group C or elastase (Group E and a sham operation group (Sham Group were used for the controls. Diameter was measured by serial digital subtraction angiography imaging on days 5, 15 and 30. Animals were sacrificed on day 5 and day 30 for histopathological and immunohistochemical studies. RESULTS: All animals in Group CE developed aneurysm, with an average dilation ratio of 65.3% ± 8.9% on day 5, 86.5% ± 28.7% on day 15 and 203.6% ± 39.1% on day 30. No aneurysm was found in Group C, and only one aneurysm was seen on day 5 in Group E. Group CE exhibited less intima-media thickness, endothelial recovery, elastin and smooth muscle cell (SMC content, but stronger expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and RAM11 compared to the controls. CONCLUSIONS: The novel rabbit model of AAA created by using a combination of periaortic CaCl2 and elastase incubation is simple and effective to perform and is valuable for elucidating AAA mechanisms and therapeutic interventions in experimental studies.

  10. Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.

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    Ngo, Doan Tm; Stafford, Irene; Sverdlov, Aaron L; Qi, Weier; Wuttke, Ronald D; Zhang, Yuan; Kelly, Darren J; Weedon, Helen; Smith, Malcolm D; Kennedy, Jennifer A; Horowitz, John D

    2011-02-01

    Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms and Dissections.

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    Milewicz, Dianna M; Trybus, Kathleen M; Guo, Dong-Chuan; Sweeney, H Lee; Regalado, Ellen; Kamm, Kristine; Stull, James T

    2017-01-01

    The importance of maintaining contractile function in aortic smooth muscle cells (SMCs) is evident by the fact that heterozygous mutations in the major structural proteins or kinases controlling contraction lead to the formation of aneurysms of the ascending thoracic aorta that predispose to life-threatening aortic dissections. Force generation by SMC requires ATP-dependent cyclic interactions between filaments composed of SMC-specific isoforms of α-actin (encoded by ACTA2) and myosin heavy chain (MYH11). ACTA2 and MYH11 mutations are predicted or have been shown to disrupt this cyclic interaction predispose to thoracic aortic disease. Movement of the myosin motor domain is controlled by phosphorylation of the regulatory light chain on the myosin filament, and loss-of-function mutations in the dedicated kinase for this phosphorylation, myosin light chain kinase (MYLK) also predispose to thoracic aortic disease. Finally, a mutation in the cGMP-activated protein kinase (PRKG1) results in constitutive activation of the kinase in the absence of cGMP, thus driving SMC relaxation in part through increased dephosphorylation of the regulatory light chain and predisposes to thoracic aortic disease. Furthermore, SMCs cannot generate force without connections to the extracellular matrix through focal adhesions, and mutations in the major protein in the extracellular matrix, fibrillin-1, linking SMCs to the matrix also cause thoracic aortic disease in individuals with Marfan syndrome. Thus, disruption of the ability of the aortic SMC to generate force through the elastin-contractile units in response to pulsatile blood flow may be a primary driver for thoracic aortic aneurysms and dissections.

  12. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.

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    Guo, Dong-Chuan; Pannu, Hariyadarshi; Tran-Fadulu, Van; Papke, Christina L; Yu, Robert K; Avidan, Nili; Bourgeois, Scott; Estrera, Anthony L; Safi, Hazim J; Sparks, Elizabeth; Amor, David; Ades, Lesley; McConnell, Vivienne; Willoughby, Colin E; Abuelo, Dianne; Willing, Marcia; Lewis, Richard A; Kim, Dong H; Scherer, Steve; Tung, Poyee P; Ahn, Chul; Buja, L Maximilian; Raman, C S; Shete, Sanjay S; Milewicz, Dianna M

    2007-12-01

    The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta.

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

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    Gao, Yuan Z; Saphirstein, Robert J; Yamin, Rina; Suki, Bela; Morgan, Kathleen G

    2014-10-15

    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 N(G)-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.

  14. Immersed smoothed finite element method for fluid-structure interaction simulation of aortic valves

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    Yao, Jianyao; Liu, G. R.; Narmoneva, Daria A.; Hinton, Robert B.; Zhang, Zhi-Qian

    2012-12-01

    This paper presents a novel numerical method for simulating the fluid-structure interaction (FSI) problems when blood flows over aortic valves. The method uses the immersed boundary/element method and the smoothed finite element method and hence it is termed as IS-FEM. The IS-FEM is a partitioned approach and does not need a body-fitted mesh for FSI simulations. It consists of three main modules: the fluid solver, the solid solver and the FSI force solver. In this work, the blood is modeled as incompressible viscous flow and solved using the characteristic-based-split scheme with FEM for spacial discretization. The leaflets of the aortic valve are modeled as Mooney-Rivlin hyperelastic materials and solved using smoothed finite element method (or S-FEM). The FSI force is calculated on the Lagrangian fictitious fluid mesh that is identical to the moving solid mesh. The octree search and neighbor-to-neighbor schemes are used to detect efficiently the FSI pairs of fluid and solid cells. As an example, a 3D idealized model of aortic valve is modeled, and the opening process of the valve is simulated using the proposed IS-FEM. Numerical results indicate that the IS-FEM can serve as an efficient tool in the study of aortic valve dynamics to reveal the details of stresses in the aortic valves, the flow velocities in the blood, and the shear forces on the interfaces. This tool can also be applied to animal models studying disease processes and may ultimately translate to a new adaptive methods working with magnetic resonance images, leading to improvements on diagnostic and prognostic paradigms, as well as surgical planning, in the care of patients.

  15. Relaxant Effects of Matrine on Aortic Smooth Muscles of Guinea Pigs

    Institute of Scientific and Technical Information of China (English)

    JIE ZHENG; PING ZHENG; XU ZHOU; LIN YAN; RU ZHOU; XUE-YAN FU; GUI-DONG DAI

    2009-01-01

    Objectives To determine whether matrine, a kind of traditional Chinese medicinal alkaloid, can relax the aortic smooth muscles isolated from guinea pigs and to investigate the mechanism of its relaxant effects. Methods Phenylephrine or potassium chloride concentration-dependent relaxation response of aortic smooth muscles to matrine was studied in the precontracted guinea pigs. Results Matrine (lx104 mol/L-3.3x10-3mol/L) relaxed the endothelium-denuded aortic rings pre-contracted sub-maximally with phenylephrine, in a concentration-dependent manner, and its pre-incubation (3.3x10-3mol/L) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anti-contractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide (10-5mol/L), either by the non-selective K+channel blocker tetraethylammonium (103mol/L), or by theβ-antagonist propranolol (105 mol/L). In either "normal" or "Ca2+-free'' bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3x103 mol/L), indicating that the vasorelaxation was due to inhibition of intracellular and extracellular Ca2+ mobilization. Conclusion Matrine inhibits phenylephrine-induced contractions by inhibiting activation of a-adrenoceptor and interfering with the release of intracellular Ca2+ and the influx of extracellular Ca2+.

  16. Experimental modulation of the plasmalemmal microfluidity. Studies on endothelial and aortic smooth muscle cells.

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    Badea, M; Jinga, V; Hörer, O

    1984-01-01

    The microfluidity of cell membranes has been modified experimentally in endothelial cells and smooth muscle cells of bovine or monkey aorta cultured in vitro. Microfluidity was estimated by fluorescence depolarization measurements of diphenyl-hexatriene (DPH)-labelled cells. In both types of cells investigated, the arachidonic acid at concentration of 90 microM induced an increase in the microfluidity by 26-53% whereas the cholesterol at the same concentration produced a decrease in the microfluidity by 16-25%. The oleic acid in the range of 30 to 90 microM increased the monkey smooth muscle cell membranes microfluidity by 21-33% but did not change the microfluidity of endothelial and bovine aortic smooth muscle cells. The stearic acid did not influence the microfluidity of either type of cells under investigation. Cortisol at 90 microM changed the microfluidity of the bovine aortic endothelial cells plasmalemma depending on the incubation time. Possible factors of error in the physical measurements due to the extracellular localization of DPH have been identified.

  17. Regulation of collagen biosynthesis in cultured bovine aortic smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Stepp, M.A.

    1986-01-01

    Aortic smooth muscles cells have been implicated in the etiology of lesions which occur in atherosclerosis and hypertension. Both diseases involve proliferation of smooth muscle cells and accumulation of excessive amounts of extracellular matrix proteins, including collagen type I and type III produced by the smooth muscle cells. To better understand the sites of regulation of collagen biosynthesis and to correlate these with the growth rate of the cells, cultured bovine aortic smooth muscle cells were studied as a function of the number of days (3 to 14) in second passage. Cells grew rapidly up to day 6 when confluence was reached. The total incorporation of (/sup 3/H)-proline into proteins was highest at day 3 and decreased to a constant level after the cultures reached confluence. In contrast, collagen protein production was lowest before confluence and continued to increase over the entire time course of the experiments. cDNA clones for the ..cap alpha..1 and ..cap alpha..2 chains of type I and the ..cap alpha..1 chain of type III collagen were used to quantitate the steady state level of collagen mRNAs. RNA was tested in a cell-free translation system. Changes in the translational activity of collagen mRNAs parallelled the observed increases in collagen protein production. Thus, at later time points, collagen mRNAs are more active in directing synthesis of preprocollagens, even though less collagen mRNA is present. The conclusion is that the site of regulation of the expression of collagen genes is a function of the growth rate of cultured smooth muscle cells.

  18. Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch.

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    Jing Zhao

    Full Text Available Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1 cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2 cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK and p38 activation with peaks at 10 min; (3 azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4 SP600125 (a JNK inhibitor and SB203580 (a p38 inhibitor protected against stretch-induced RASMC death; (5 Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.

  19. Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

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    Joshua E Basford

    Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

  20. Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells.

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    Baldini, P M; De Vito, P; Fraziano, M; Mattioli, P; Luly, P; Di Nardo, P

    2002-10-01

    Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement.

  1. A GROWTH INHIBITOR SECRETED FROM CULTURED RABBIT SMOOTHMUSCLE CELLS IS DISTINCT FROM TGF-β

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To ascertain whether the growth inhibitor in conditioned medium from cultured rabbit arte rial cells is distinct from TGF-β. Methods Rabbit aortic smooth muscle ceils were grown from explained segments of the aorta. Conditioned medium from cultured rabbit aortic smooth muscle ceils and anti-TGF-β were employed in this study. Smooth muscle cell proliferation was measured by XTT detection (Boehringer Mannheim). Results Acidified conditioned medium from smooth muscle ceils had significantly stronger effects of growth inhibition than controls, and anti-TGF-β did not affect the growth inhibitory effect of conditioned medium from cultured rabbit arterial smooth muscle cells. Conclusion The growth inhibiting substance in conditioned medium from cultured rabbit aortic smooth muscle cells is distinct from TGF-β.

  2. Relaxant effect of an estrone derivate EA303 on isolated colonic smooth muscle of rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHU Lan; FU Shou-ting; CHEN Guo-liang; ZHOU Qian-qian

    2008-01-01

    Objective To study the relaxant effect mechanism of an estrone derivate EA303 on isolate colonic smooth muscle of rabbits. Methods Preparations of the isolated colonic smooth muscle of rabbits were prepared. The effect of EA303 on potassium channel, β receptor and prostaglandin were studied by observing the difference of relaxant dose-effect curves of EA303 on preparations pre-contracted with BaCl3, High K+ solution and Acetylcholine chloride (ACh) in the absence or presence incubation with glibenclamide (10 μM), propranolol (0.1 μM) and Indometacin (10 μM). Results The relaxant effect of EA303 on contraction caused by BaCl2 and High K+ solution were weakened by glibenclamide inhibiting the opening of K+ channel while the relaxant effect of that on contraction caused by ACh was strengthened, after adding propranolol inhabiting β receptor, EA303 attenuated the relaxant action on contraction caused by BaCl2. EA303 had some relaxant impact on contraction induced by High K+ solution after adding indometacin inhabiting the synthesis the prostaglandin (PG). Conclusions The relaxant effect of EA303 on isolated colonic smooth muscle of rabbits may be related with PG synthesis enzyme, potassium channel and β receptor.

  3. Suppression of angiotensin II stimulated responses in aortic vascular smooth muscle cells of experimental cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Functional responses to angiotensin II(AT-II) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats.Our data showed that AT-II-stimulated extracellular acidification rate (ECAR),which was measured by Cytosesor microphysiometry,was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals.The ability of AT-II to promote formation of inositol phosphates,the second messenger produced by the activation of Gq-coupled receptors,was also considerably suppressed in the cirrhotic VSMCs.Furthermore,the maximal p42/44 MAPK phosphorylation stimulated by AT-II was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs.Taken together,our data clearly demonstrated that the functional responses to AT-II was severely suppressed in aortic VSMCs in cirrhosis,indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.

  4. Relaxation effects of matrine on guinea-pig aortic smooth muscles

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jie; ZHENG Ping; ZHOU Xu; YAN Lin; ZHOU Ru; FU Xue-yan; DAI Gui-dong

    2008-01-01

    Objective The present in vivo study was undertaken to determine whether matrine, a kind of traditional Chinese medicinal alkaloid, would relax the isolated guinea pig aortic smooth muscles, if so, to investigate the mechanism involved. Methods The concentration-dependent relaxation response to matrine was studied in phenylephrine or potassium chloride precontracted guinea pig aortic rings. Results Matrine (1× 10-4M- 3.3×10-3 M) relaxed the endothelium denuded aortic rings precontracted submaximally with phenylephrine, in a concentration-dependent manner, and it's preincubation (3.3×10-3 M) produced a significant rightward shift in the phenylephrine dose-response curve, but had no effects on the potassium chloride-induced contraction. The anticontractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide (10-5 M), the non-selective K+ channel blocker tetraethylammonium (10-3 M), as well as the β-antagonist propranolol (10-5 M). In either "normal" or "Ca2+ -free" bathing medium, the phenylephrine-induced contraction was attenuated by matrine (3.3×10-3 M), indieating the vasorelaxation was due to inhibit of intracellular and extracellular Ca2+ mobilization. Conclusions The results obtained clearly demonstrated that matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with both the release of intracellular Ca2+ and the influx of extracellular Ca2+.

  5. Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells.

    Science.gov (United States)

    Chen, Feng; Zhang, ZhenDong; Zhu, XianHua

    2015-11-05

    Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.

  6. Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

    Science.gov (United States)

    Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

    2000-01-01

    This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (Pmuscle cells is likely due to transient membrane disruption on initiation of flow.

  7. Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

    Science.gov (United States)

    Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

    2000-01-01

    This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (Pmuscle cells is likely due to transient membrane disruption on initiation of flow.

  8. Differential effect of 17-beta-estradiol on smooth muscle cell and aortic explant MMP2.

    Science.gov (United States)

    Woodrum, Derek T; Ford, John W; Cho, Brenda S; Hannawa, Kevin K; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2009-07-01

    The present investigation tested the hypothesis that intrinsic gender-related differences exist in rat aortic smooth muscle cell matrix metalloproteinase 2 (MMP2). This investigation comprised 3 sets of experiments. Experiment I: Adult male and female rat aortic smooth muscle cells (RASMCs) at passages 4-8 were stimulated in serum-free media for 48 h with interleukin(IL)1beta at doses encountered in human abdominal aortic aneurysms (2 ng/mL). Messenger RNA was extracted from the RASMCs, and gene expression of MMP2 and tissue inhibitor of metalloproteinase 2 (TIMP2), a major MMP2 inhibitor, was measured by real-time polymerase chain reaction. MMP2 protein levels in conditioned media were measured by Western blotting, and MMP2 and TIMP2 activity quantified by standard and reverse gelatin zymography. Experiment II: Male and female RASMCs were incubated for 48 h in Dulbecco's modified Eagler's medium containing IL-1beta and 17-beta-estradiol at doses from 1x10(-10) to 1x10(-6) molar. MMP2 activity in the conditioned media was then determined. Experiment III: Male rats underwent sustained 17-beta-estradiol exposure for 21 d using extended-release, subcutaneously implanted pellets prior to sacrifice and aortic explantation. Aortas from males, females, and estradiol-treated males were stimulated with IL-1beta for 48-h, and MMP2 activity in the conditioned media was determined. Experiment I: MMP2 gene expression was 3-fold higher in male compared with female IL-1beta stimulated RASMCs (P<0.0001). MMP2:TIMP2 gene expression ratio was 7.5-fold greater in male versus female RASMCs. MMP2 protein levels were 3-fold higher (2.68 versus 0.96 o.d./mg total protein, P=0.003) in male versus female RASMCs. Gelatinolytic activity was more than 6-fold higher (15,010 versus 2,472 o.d./mg total protein, P=0.002) in male versus female RASMCs. Experiment II: MMP2 activity in male and female RASMCs was not altered by a wide range of 17-beta-estradiol concentrations. Experiment III: When

  9. Differential Effect of 17-β-Estradiol on Smooth Muscle Cell and Aortic Explant MMP2

    Science.gov (United States)

    Woodrum, Derek T.; Ford, John W; Cho, Brenda S.; Hannawa, Kevin K.; Stanley, James C.; Henke, Peter K.; Upchurch, Gilbert R.

    2010-01-01

    Objective The present investigation tested the hypothesis that intrinsic gender-related differences exist in rat aortic smooth muscle cell MMP2. Methods This investigation comprised three sets of experiments. Experiment I: Adult male and female rat aortic smooth muscle cells (RASMCs) at passages 4–8 were stimulated in serum-free media for 48 hours with IL1β at doses encountered in human AAAs (2ng/mL). Messenger RNA was extracted from the RASMCs, and gene expression of MMP2 and tissue inhibitor of metalloproteinase2 (TIMP2),a major MMP2 inhibitor, was measured by real-time polymerase chain reaction. MMP2 protein levels in conditioned media were measured by Western Blotting, and MMP2 and TIMP2 activity quantified by standard and reverse gelatin zymography. Experiment II: Male and female RASMCs were incubated for 48 hrs in DMEM containing IL-1β and 17-β-estradiol at doses from 1×10−10 to 1×10−6 molar. MMP2 activity in the conditioned media was then determined. Experiment III: Male rats underwent sustained 17-β-estradiol exposure for 21 days using extended-release, subcutaneously implanted pellets prior to sacrifice and aortic explantation. Aortas from males, females, and estradiol-treated males were stimulated with IL1β for 48 hrs, and MMP2 activity in the conditioned media was determined. Results Experiment I: MMP2 gene expression was 3-fold higher in male compared to female IL1β stimulated RASMCs (P<0.0001). MMP2: TIMP2 gene expression ratio was 7.5 fold greater in male vs. female RASMCs. MMP2 protein levels were 3-fold higher (2.68 vs. 0.96 O.D./mg total protein, P=0.003) in male vs. female RASMCs. Gelatinolytic activity was more than 6-fold higher (15,010 vs. 2,472 O.D./mg total protein, P=0.002) in male vs. female RASMCs. Experiment II: MMP2 activity in male and female RASMCs was not altered by a wide range of 17-β-estradiol concentrations. Experiment III: When pre-treated with 17-β-estradiol, MMP2 activity in the media of male rat whole-aortic

  10. Effect of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    刘曜蓉

    2013-01-01

    Objective To investigate the impact of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells (HASMCs) .Methods Uremic serum was incubated at 37℃for 3days.Calcium phosphate crystals and uremic supernatant were isolated from uremic serum by ultracentrifugation.

  11. TGFBR2 mutations alter smooth muscle cell phenotype and predispose to thoracic aortic aneurysms and dissections

    Science.gov (United States)

    Inamoto, Sakiko; Kwartler, Callie S.; Lafont, Andrea L.; Liang, Yao Yun; Fadulu, Van Tran; Duraisamy, Senthil; Willing, Marcia; Estrera, Anthony; Safi, Hazim; Hannibal, Mark C.; Carey, John; Wiktorowicz, John; Tan, Filemon K.; Feng, Xin-Hua; Pannu, Hariyadarshi; Milewicz, Dianna M.

    2010-01-01

    Aims Transforming growth factor-β (TGF-β) signaling is critical for the differentiation of smooth muscle cells (SMCs) into quiescent cells expressing a full repertoire of contractile proteins. Heterozygous mutations in TGF-β receptor type II (TGFBR2) disrupt TGF-β signaling and lead to genetic conditions that predispose to thoracic aortic aneurysms and dissections (TAADs). The aim of this study is to determine the molecular mechanism by which TGFBR2 mutations cause TAADs. Methods and results Using aortic SMCs explanted from patients with TGFBR2 mutations, we show decreased expression of SMC contractile proteins compared with controls. Exposure to TGF-β1 fails to increase expression of contractile genes in mutant SMCs, whereas control cells further increase expression of these genes. Analysis of fixed and frozen aortas from patients with TGFBR2 mutations confirms decreased in vivo expression of contractile proteins relative to unaffected aortas. Fibroblasts explanted from patients with TGFBR2 mutations fail to transform into mature myofibroblasts with TGF-β1 stimulation as assessed by expression of contractile proteins. Conclusions These data support the conclusion that heterozygous TGFBR2 mutations lead to decreased expression of SMC contractile protein in both SMCs and myofibroblasts. The failure of TGFBR2-mutant SMCs to fully express SMC contractile proteins predicts defective contractile function in these cells and aligns with a hypothesis that defective SMC contractile function contributes to the pathogenesis of TAAD. PMID:20628007

  12. Induction of Timp1 in smooth muscle cells during development of abdominal aortic aneurysms.

    Science.gov (United States)

    Bumdelger, Batmunkh; Kokubo, Hiroki; Kamata, Ryo; Fujii, Masayuki; Ishida, Mari; Ishida, Takafumi; Yoshizumi, Masao

    2013-09-01

    Abdominal aortic aneurysm (AAA) is known to develop mainly by the increased diameter of aorta through metalloproteinases (MMPs). Although activities of MMPs are tightly regulated by the presence of tissue inhibitor of MMPs (TIMPs) and imbalances between MMPs and TIMPs may serve to fragility of arterial wall, little is known about TIMPs behavior in aneurysmal formation. Here, we utilized a murine experimental AAA model, and found that by immunohistochemical analysis, Timp1 as and Timp1 mRNA levels was also revealed in aortic tissue in AAA by RT-PCR. In cultured vascular smooth muscle cells (SMCs), Tumor Necrosis Factor (TNF)-alpha significantly activated both Mmp9 and Timp1 expression, and they were blocked by Jun kinase inhibitor (SP600125) in a dose-dependent manner. Interestingly, a proteasome inhibitor (MG132), which is known as an agent for inhibition of the nuclear factor-kappa B (NF-kappaB), significantly inhibited the TNF-alpha-induced expression of Timp1, whereas MG132, which also works as an activator of c-Jun/AP-1 pathway, strongly increased Mmp9. Taken together, inflammatory cytokines, including TNF-alpha, may simultaneously induce MMPs and TIMPs for the remodeling of the medial layer, leading to the increased diameter of the aorta, the aneurysm.

  13. Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.

    Directory of Open Access Journals (Sweden)

    Giuseppe Cafueri

    Full Text Available BACKGROUND: Abdominal aortic aneurysm (AAA is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC, vascular smooth muscle cells (VSMC, and epidermal cells from patients with AAA in comparison with matched controls. METHODS: TL was assessed using a modification of quantitative (Q-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG. RESULTS AND CONCLUSIONS: Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.

  14. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

    Science.gov (United States)

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  15. [Determining the aortic and renal hemodynamic effects of propofol on rabbits using Doppler ultrasonography].

    Science.gov (United States)

    Apan, Alpaslan; Karadeniz Bilgili, M Yasemin; Cağlayan, Fatma

    2004-03-01

    The hemodynamic effects of propofol-fentanyl anesthesia were known to reduce arterial pressure and heart rate. We aimed to determine the effects of propofol-fentanyl anesthesia on renal artery blood flow and aorta by using Doppler ultrasonography on an animal model. The study was conducted on 8 male New Zaeland White strain rabbits. The initial aortic and renal hemodynamic measurements were determined on animals using ketamin anesthesia. Later the right femoral arteries were cannulated for determining arterial blood pressure and pulse oximetry was followed from the ear. Propofol 5-7 mg/kg with fentanyl 1-2 microg/kg was injected via the ear vein. Doppler parameters (RI, RI, Vmax, Vmin) of the renal artery and aorta were determined after the anesthesia. According to the basal measurements, arterial blood pressure and breath rates declined significantly (27% and 53% respectively, p<0.05); however there were no statistical alteration of aortic and renal artery Doppler parameters. Anesthesia induced by propofol-fentanyl did not induce a statistically significant difference in Doppler parameters obtained from the renal artery and aorta. It is clinically important to know that determining the changes in RI and PI during the postoperative period is not related to the propofol-fentanyl anesthesia.

  16. Co-cultivation of human aortic smooth muscle cells with epicardial adipocytes affects their proliferation rate.

    Science.gov (United States)

    Ždychová, J; Čejková, S; Králová Lesná, I; Králová, A; Malušková, J; Janoušek, L; Kazdová, L

    2014-01-01

    The abnormal proliferation of vascular smooth muscle cells (VSMC) is thought to play a role in the pathogenesis of atherosclerosis. Adipocytes produce several bioactive paracrine substances that can affect the growth and migration of VSMCs. Our study focuses on the direct effect of the bioactive substances in conditioned media (CM) that was obtained by incubation with primary adipocyte-derived cell lines, including cell lines derived from both preadipocytes and from more mature cells, on the proliferation rate of human aortic smooth muscle cells (HAoSMCs). We used a Luminex assay to measure the adipokine content of the CM and showed that there was a higher concentration of monocyte chemoattractant protein-1 in renal preadipocyte-CM compared with the HAoSMC control (p<0.5). The addition of both renal preadipocyte- and epicardial adipocyte- CM resulted in the elevated production of vascular endothelial growth factor compared with the control HASoSMC CM (p<0.001). The adiponectin content in renal adipocyte-CM was increased compared to all the remaining adipocyte-CM (p<0.01). Moreover, the results showed a higher proliferation rate of HAoSMCs after co-culture with epicardial adipocyte-CM compared to the HAoSMC control (p<0.05). These results suggest that bioactive substances produced by adipocytes have a stimulatory effect on the proliferation of VSMCs.

  17. Function and role of voltage-gated sodium channel NaV1.7 expressed in aortic smooth muscle cells.

    Science.gov (United States)

    Meguro, Kentaro; Iida, Haruko; Takano, Haruhito; Morita, Toshihiro; Sata, Masataka; Nagai, Ryozo; Nakajima, Toshiaki

    2009-01-01

    Voltage-gated Na(+) channel currents (I(Na)) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of I(Na), its functional role, pathophysiology in cultured human (hASMCs) and rabbit aortic smooth muscle cells (rASMCs), and its association with vascular intimal hyperplasia. In whole cell voltage clamp, I(Na) was observed at potential positive to -40 mV, was blocked by tetrodotoxin (TTX), and replacing extracellular Na(+) with N-methyl-d-glucamine in cultured hASMCs. In contrast to native aorta, cultured hASMCs strongly expressed SCN9A encoding Na(V)1.7, as determined by quantitative RT-PCR. I(Na) was abolished by the treatment with SCN9A small-interfering (si)RNA (P SCN9A siRNA significantly inhibited cell migration (P SCN9A in cultured rASMCs and aorta 48 h after balloon injury but not in native aorta. In conclusion, these studies show that I(Na) is expressed in cultured and diseased conditions but not in normal aorta. The Na(V)1.7 plays an important role in cell migration, endocytosis, and secretion. Na(V)1.7 is also expressed in aorta after balloon injury, suggesting a potential role for Na(V)1.7 in the progression of intimal hyperplasia.

  18. Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function.

    Science.gov (United States)

    OBJECTIVE: Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and i...

  19. Increased apoptosis and decreased density of medial smooth muscle cells in human abdominal aortic aneurysms

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian张健; Jan Schmidt; Eduard Ryschich; Hardy Schumacher; Jens R Allenberg

    2003-01-01

    Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P<0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF, P<0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA, which may profoundly influence the development of AAA.

  20. Detection of histidine decarboxylase in rat aorta and cultured rat aortic smooth muscle cells.

    Science.gov (United States)

    Tippens, A S; Davis, S V; Hayes, J R; Bryda, E C; Green, T L; Gruetter, C A

    2004-08-01

    Having previously demonstrated release of histamine from mast-cell-deficient rat aorta, the objective of this study was to determine and localize histamine synthesis capability in the aorta by detecting histidine decarboxylase (HDC), the enzyme that catalyzes histamine formation. Experiments were conducted with nested reverse transcription-polymerase chain reaction (nRT-PCR) to detect HDC mRNA and with immunofluorescence and western blot analysis to detect HDC protein in rat aorta, cultured rat aortic smooth muscle (RASMC) and endothelial cells (RAEC). Gel electrophoresis of nRT-PCR products indicated HDC mRNA in liver, aorta and RASMC but not in RAEC or kidney. Sequence analysis confirmed that the band observed in RASMC was the target HDC amplicon. Immunofluorescence indicated the presence of HDC protein in RASMC and not in RAEC. Western Blot analysis revealed HDC protein (55 kDa) in liver, aorta, RASMC but not in RAEC or kidney. The results of this study are the first to demonstrate the presence of HDC mRNA and protein in rat aorta and more specifically in RASMC, indicative of their capability to synthesize histamine. Copyright 2004 Birkhäuser Verlag, Basel

  1. Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Liu, Yaorong; Zhang, Lin; Ni, Zhaohui; Qian, Jiaqi; Fang, Wei

    2016-11-01

    Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals' inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day crystals with pyrophosphate incubation prevented calcium deposition and bone-calcifying gene over-expression increased by uremic serum. CaP crystals, rather than the rest of uremic serum, were responsible for these effects. Uremic serum accelerates arterial calcification by mediating osteogenic differentiation. This effect might be mainly attributed to the CaP crystal content.

  2. Characterization of putative receptors specific for quercetin on bovine aortic smooth-muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, S.C.; Becker, C.G.

    1986-03-01

    The authors have reported that tobacco glycoprotein (TGP), rutin-bovine serum albumin conjugates (R-BSA), quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells (SMC). To investigate whether there are binding sites or receptors for these polyphenol-containing molecules on SMC, the authors have synthesized /sup 125/I-labeled rutin-bovine serum albumin ((/sup 125/I)R-BSA) of high specific activity (20 Ci/mmol). SMC were isolated from a bovine thoracic aorta and maintained in Eagle's minimum essential medium with 10% calf serum in culture. These SMC at early subpassages were suspended (3-5 x 10/sup 7/ cells/ml) in phosphate-buffered saline and incubated with (/sup 125/I)R-BSA (10 pmol) in the presence or absence of 200-fold unlabeled R-BSA, TGP, BSA, rutin, quercetin or related polyphenols, and catecholamines. Binding of (/sup 125/I)R-BSA to SMC was found to be reproducible and the radioligand was displaced by R-BSA, and also by TGP, rutin, quercetin, and chlorogenic acid, but not by BSA, ellagic acid, naringin, hesperetin, dopamine, epinephrine, or isoproterenol. The binding was saturable, reversible, and pH-dependent. These results demonstrate the presence of specific binding sites for quercetinon arterial SMC.

  3. Melatonin reduces peroxynitrite-induced injury in aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Jun-lin ZHOU; Xiao-guang ZHU; Yi-ling LING; Qing LI

    2004-01-01

    AIM: To study the protective role of melatonin (MT) in peroxynitrite-induced injury in cultured aortic smooth muscular cells (ASMC). METHODS: Peroxynitrite was synthesized chemically with a quenched flow reaction.Cells were exposed to peroxynitrite 500 pmol/L for 1 h in the absence or presence of various concentrations of MT 100, 300, and 500 μmol/L. Nitrotyrosine (NT), a specific "footprint" of peroxynitrite formation, was detected by immunohistochemical technique. The DNA damage was assayed by TUNEL technique. The levels of MDA in the medium and cell viability were measured. RESULTS: Incubation of ASMC with peroxynitrite 500 μmol/L for 1 h elicited the increase in the extent of immunostaining for NT, the rate of the TUNEL-positive cell, the content of MDA in the medium, and the number of dead cell. Pretreatment of ASMC with MT 100-500 μmol/L decreased these peroxynitrite-induced changes in a concentration-dependent manner. CONCLUSION: MT attenuated the injury induced by peroxynitrite in ASMC.

  4. Monocyte migration into the subendothelial space of a coculture of adult human aortic endothelial and smooth muscle cells.

    OpenAIRE

    Navab, M; Hough, G P; Stevenson, L W; Drinkwater, D C; Laks, H; Fogelman, A M

    1988-01-01

    Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were isolated and used to form a multilayer of EC-SMC separated by a layer of collagen. SMC and/or collagen layers exerted minimal effects on Na+ transport but impeded the transport of LDL. The presence of an endothelial monolayer markedly reduced the transport of Na+ and LDL. When monocytes were presented to the complete coculture, in the absence of added chemoattractant, one monocyte entered the subendothelial space for every...

  5. Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Tsutsui, H.; Tomoike, H.; Nakamura, M. (Kyushu Univ., Fukuoka (Japan))

    1990-08-01

    Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using ({sup 14}C)antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of ({sup 14}C)antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.

  6. Relaxation of rabbit cavernous smooth muscle to 17β-estradiol: a non-genomic, NO-independent mechanism

    Institute of Scientific and Technical Information of China (English)

    Sae-ChulKim; Kyung-KunSeo; Soon-ChulMyung; MooYeolLee

    2004-01-01

    Aim: To investigate whether estrogen was involved in relaxation of rabbit cavernous smooth muscle.Methods: Relaxation response of the rabbit cavernous smooth muscles to 17β-estradiol (0.3, 3, 30 and 300 nmol/L) were observed in vitro. The response of the muscle strips to estrogen after incubation with either actinomycin D (10μmol/L) or L-NAME (10μmol/L) were also evaluated. Inside-out mode of patch clamp in a single smooth muscle cell was applied to investigate the Maxi-K channel activities. Results: Estrogen caused a dose-dependent relaxation of the strips precontracted with norepinephrine. The maximal response was noted about 10 minutes after treatment. Theestrogen-induced relaxation was prevented by neither actinomycin D nor L-NAME, suggesting that the response was not mediated by gene transcription or nitric oxide (NO). Application of 17β-estradiol increased the Maxi-K channelactivities. Conclusion: 17β-estradiol may be involved in relaxation of rabbit cavernous smooth muscles via a nongenomic and NO independent mechanism. 17β-estradiol stimulates Maxi-K channel of the rabbit cavernous myocyte.

  7. Vasorelaxant effects of aqueous leaf extract of Tridax procumbens on aortic smooth muscle isolated from the rat.

    Science.gov (United States)

    Salahdeen, Hussein M; Murtala, Babatunde A

    2012-01-01

    Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

  8. Mechanism of angiotensin II-induced arachidonic acid metabolite release in aortic smooth muscle cells: involvement of phospholipase D.

    Science.gov (United States)

    Shinoda, J; Kozawa, O; Suzuki, A; Watanabe-Tomita, Y; Oiso, Y; Uematsu, T

    1997-02-01

    In a previous study, we have shown that angiotensin II (Ang II) activates phosphatidylcholine-hydrolyzing phospholipase D due to Ang II-induced Ca2+ influx from extracellular space in subcultured rat aortic smooth muscle cells. In the present study, we have investigated the role of phospholipase D in Ang II-induced arachidonic acid (AA) metabolite release and prostacyclin synthesis in subcultured rat aortic smooth muscle cells. Ang II significantly stimulated AA metabolite release in a concentration-dependent manner in the range between 1 nmol/I and 0.1 mumol/I. D.L.-Propranolol hydrochloride (propranolol), an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the Ang II-induced release of AA metabolites. The Ang II-induced AA metabolite release was reduced by chelating extracellular Ca2+ with EGTA. Genistein, an inhibitor of protein tyrosine kinases, significantly suppressed the Ang II-induced AA metabolite release. 1,6-Bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267), a potent and selective inhibitor of diacylglycerol lipase, significantly inhibited the Ang II-induced AA metabolite release. Both propranolol and RHC-80267 inhibited the Ang II-induced synthesis of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin. The synthesis was suppressed by genistein. These results strongly suggest that the AA metabolite release induced by Ang II is mediated, at least in part, through phosphatidylcholine hydrolysis by phospholipase D activation in aortic smooth muscle cells.

  9. INHIBITORY EFFECT OF FLUVASTATIN ON AORTIC INTIMAL THICKENING IN NORMOCHOLESTEROLEMIC RABBITS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. The anti-atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter-induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods. Fifty-six rabbits were randomly divided into eight groups(n = 7, each). Fluvastatin was given mixed with food at daily dose of 8mg/kg starting 5 days before catheterization, Light microscope, immunohistochemistry, transmis-sion electron microecope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC)proliferation and apoptosis, as well as oncogene expression in vascular wall. Results. At day 10 and day 15 after catheter induced denudation intima/media(I/M)thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of α-SM-actin-positive cells. In rabbits given flu-vastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvas-tatin. The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expres-sion. Conclusion. Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.

  10. Bepridil (CERM-1978) an verapamil depression of contractions of rabbit aortic rings.

    Science.gov (United States)

    Mras, S; Sperelakis, N

    1981-01-01

    Isolated rings (about 1 mm wide) of rabbit ascending aorta were stimulated to contract by norepinephrine (NE), increased extracellular potassium ion concentration, or electrical stimulation. When tested 20 min after addition, bepridil (CERM-1978) (10(-5)-10(-6) M), a new antianginal agent, and verapamil (10(-5)-10(-6) M) depressed the contractile responses to high K+ (30 mM) and NE (10(-6) M). Bepridil was almost as potent as verapamil in this action. Responses to strong electrical field stimulation were not affected by either agent. The depressed responses to NE in Ca-free EGTA-containing solutions were not further affected by bepridil or verapamil. Contractile responses to NE obtained from depolarized tissues, however, were markedly depressed by bepridil. These results suggest that bepridil, like verapamil, acts to inhibit contractions of vascular smooth muscle by decreasing influx of extracellular Ca++. In depolarized vascular smooth muscle, bepridil may also exert an effect to depress contractions supported by intracellular Ca++ release.

  11. Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine

    Energy Technology Data Exchange (ETDEWEB)

    Cox, L.R.; Murphy, S.K.; Ramos, K. (Philadelphia College of Pharmacy and Science, PA (USA))

    1990-08-01

    Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. 32P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of (3H)myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced 32P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in (3H)myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/ml), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/ml), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. We conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism.

  12. Fluid-Structure Interaction Study of Transcatheter Aortic Valve Dynamics Using Smoothed Particle Hydrodynamics.

    Science.gov (United States)

    Mao, Wenbin; Li, Kewei; Sun, Wei

    2016-12-01

    Computational modeling of heart valve dynamics incorporating both fluid dynamics and valve structural responses has been challenging. In this study, we developed a novel fully-coupled fluid-structure interaction (FSI) model using smoothed particle hydrodynamics (SPH). A previously developed nonlinear finite element (FE) model of transcatheter aortic valves (TAV) was utilized to couple with SPH to simulate valve leaflet dynamics throughout the entire cardiac cycle. Comparative simulations were performed to investigate the impact of using FE-only models vs. FSI models, as well as an isotropic vs. an anisotropic leaflet material model in TAV simulations. From the results, substantial differences in leaflet kinematics between FE-only and FSI models were observed, and the FSI model could capture the realistic leaflet dynamic deformation due to its more accurate spatial and temporal loading conditions imposed on the leaflets. The stress and the strain distributions were similar between the FE and FSI simulations. However, the peak stresses were different due to the water hammer effect induced by the fluid inertia in the FSI model during the closing phase, which led to 13-28% lower peak stresses in the FE-only model compared to that of the FSI model. The simulation results also indicated that tissue anisotropy had a minor impact on hemodynamics of the valve. However, a lower tissue stiffness in the radial direction of the leaflets could reduce the leaflet peak stress caused by the water hammer effect. It is hoped that the developed FSI models can serve as an effective tool to better assess valve dynamics and optimize next generation TAV designs.

  13. Olfactory ensheathing cells of hamsters, rabbits, monkeys, and mice express α-smooth muscle actin.

    Science.gov (United States)

    Rawji, Khalil S; Zhang, Shannon X; Tsai, Ying-Yu; Smithson, Laura J; Kawaja, Michael D

    2013-07-12

    Olfactory ensheathing cells (OECs) are the chief glial population of the mammalian olfactory nervous system, residing in the olfactory mucosa and at the surface of the olfactory bulb. We investigated the neurochemical features of OECs in a variety of mammalian species (including adult hamsters, rabbits, monkeys, and mice, as well as fetal pigs) using three biomarkers: α-smooth muscle actin (αSMA), S100β, and glial fibrillary acidic protein (GFAP). Mucosal and bulbar OECs from all five mammalian species express S100β. Both mucosal and bulbar OECs of monkeys express αSMA, yet only bulbar OECs of hamsters and only mucosal OECs of rabbits express αSMA as well. Mucosal OECs, but not bulbar OECs, also express GFAP in hamsters and monkeys; mice, by comparison, have only a sparse population of OECs expressing GFAP. Though αSMA immunostaining is not detected in OECs of adult mice, GFAP-expressing mucosal OECs isolated from adult mice do coexpress αSMA in vitro. Moreover, mucosal OECs from adult mutant mice lacking αSMA expression display perturbed cellular morphology (i.e., fewer cytoplasmic processes extending among the hundreds of olfactory axons in the olfactory nerve fascicles and nuclei having degenerative features). In sum, these findings highlight the efficacy of αSMA and S100β as biomarkers of OECs from a variety of mammalian species. These observations provide definitive evidence that mammalian OECs express the structural protein αSMA (at various levels of detection), which appears to play a pivotal role in their ensheathment of olfactory axons.

  14. Calcium ion requirement for acetylcholine-stimulated breakdown of triphosphoinositide in rabbit iris smooth muscle.

    Science.gov (United States)

    Akhtar, R A; Abdel-Latif, A A

    1978-03-01

    Previous studies from this laboratory have established that addition of acetylcholine (ACh) or norepinephrine to 32P-labeled rabbit iris smooth muscle increases significantly the breakdown of triphosphoinositide (TPI) and that these stimulatory effects are blocked by atropine and phentolamine, respectively. The present studies were undertaken in order to show the effect of Ca++ on the ACh-stimulated breakdown of TPI ("TPI effect") in this tissue. Paired iris smooth muscles were prelabeled with 32Pi for 30 minutes at 37 degrees C in Ca++-free iso-osmotic salt medium. The prelabeled irises were then washed and incubated for 10 minutes in nonradioactive Ca++-free medium which contained 10 mM 2-deoxyglucose under various conditions. The phospholipids were isolated by means of two-dimensional thin-layer chromatography and their radioactivities were determined. In the absence of Ca++, 50 micrometer ACh increased TPI breakdown and phosphatidic acid (PA) labeling by 16 and 38%, respectively. In the absence of ACh, 0.75 micrometer Ca++ increased TPI breakdown and PA labeling by 11 and 20%, respectively. When both ACh and Ca++ were added, the increase in TPI breakdown and PA labeling rose to 32 and 74%, respectively. The labeling of phosphatidylinositol was found to be insensitive to the presence of Ca++. Ca++ was determined in the iris smooth muscle and it was found to contain 3.13 mumol of Ca++ per g of tissue. This was reduced by 80% after the muscle was washed and incubated in a medium which contained 0.25 micrometer ethyleneglycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). The TPI effect was abolished by 0.25 micrometer EGTA and restored when excess Ca++ (1.25 micrometer) was added. Concentrations of Ca++ as low as 50 micrometer provoked a TPI effect. Sr++ (2 micrometer), but not Ba++ or Mn++, was found to substitute partially for Ca++. Ionophore A-23187 (20 micrometer) was found to increase the breakdown of TPI and labeling of PA by 11 and 24

  15. Single rabbit stomach smooth muscle cell myosin heavy chain SMB expression and shortening velocity.

    Science.gov (United States)

    Eddinger, T J; Meer, D P

    2001-02-01

    Isolated single smooth muscle cells (SMCs) from different regions of the rabbit stomach were used to determine a possible correlation between unloaded shortening velocity and smooth muscle (SM) myosin heavy chain (MHC) S1 head isoform composition (SMA, no head insert; SMB, with head insert). alpha-Toxin-permeabilized isolated single cells were maximally activated to measure unloaded shortening velocity and subsequently used in an RT-PCR reaction to determine the SMA/SMB content of the same cell. SM MHC SMA and SMB isoforms are uniquely distributed in the stomach with cells from the fundic region expressing little SMB (38.1 +/- 7.3% SMB; n = 16); cells from the antrum express primarily SMB (94.9 +/- 1.0% SMB; n = 16). Mean fundic cell unloaded shortening velocity was 0.014 +/- 0.002 cell lengths/s compared with 0.036 +/- 0.002 for the antrum cells. Unloaded shortening velocity in these cells was significantly correlated with their percent SMB expression (r2 = 0.58). Resting cell length does not correlate with the percent SMB expression (n = 32 cells). Previously published assays of purified or expressed SMA and SMB heavy meromyosin show a twofold difference in actin filament sliding speed in in vitro motility assays. Extrapolation of our data to 0-100% SMB would give a 10-fold range of shortening velocity, which is closer to the approximately 20-fold range reported from various SM tissues. This suggests that mechanisms in addition to the MHC S1 head isoforms regulate shortening velocity.

  16. Homocysteine and copper interact to promote type 5 phosphodiesterase expression in rabbit cavernosal smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Matthew Hotston; Jamie Y.Jeremy; Jonathon Bloor; Nick S.Greaves; Raj Persad; Giarmi Angelini; Nilima Shukla

    2008-01-01

    Aim: To study the effects of homocysteine and copper on type 5 phosphodiesterase (PDE5) expression in cavernosal vascular smooth muscle cells (CVSMCs) and to investigate superoxide (O2) derived from nicotinamide adenine dinucleotide phosphate oxidase as homocysteine and copper generate O2, and O2- upregulates PDE5 expression.Methods: CVSMCs derived from rabbit penis were incubated with homocysteine or copper chloride with or without superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (nicotinamide adenine dinucleotide phosphate inhibitor) for 16 h. The expression of PDE5 and of glyceraldehyde-3-phosphate dehydrogenase (internal standard) was assessed using Western blot analysis. In parallel, O2 was measured spectrophotometrically. Results: CuCl2alone (up to 10 μmol/L) and homocysteine alone (up to 100 μmol/L) had no effect on O2 formation in CVSMCs compared to controls. In combination, however, homocysteine and CuCl2 arkedly increased O2 formation, an effect blocked by SOD, catalase, apocynin, and sildenafil (1 μmol/L) when co-incubated over the same time course.PDE5 expression was also significantly increased in CVSMCs incubated with homocysteine and CuCl2, compared to controls. This effect was also negated by 16-h co-incubation with SOD, catalase, apocynin and sildenafil. Conclusion:This represents a novel pathogenic mechanism underlying ED, and indicates that the therapeutic actions of prolonged sildenafil use are mediated in part through inhibition of this pathway.

  17. Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve

    Directory of Open Access Journals (Sweden)

    Pamela Lazar-Karsten

    2016-04-01

    Full Text Available Thoracic aortic dilation is the most common malformation of the proximal aorta and is responsible for 1%–2% of all deaths in industrialized countries. In approximately 50% of patients with a bicuspid aortic valve (BAV, dilation of any or all segments of the aorta occurs. BAV patients with aortic dilation show an increased incidence of cultured vascular smooth muscle cell (VSMC loss. In this study, VSMC, isolated from the ascending aorta of BAV, was treated with Simian virus 40 to generate a BAV-originated VSMC cell line. To exclude any genomic DNA or cross-contamination, highly polymorphic short tandem repeats of the cells were profiled. The cells were then characterized using flow cytometry and karyotyping. The WG-59 cell line created is the first reported VSMC cell line isolated from a BAV patient. Using an RT2 Profiler PCR Array, genes within the TGFβ/BMP family that are dependent on losartan treatment were identified. Endoglin was found to be among the regulated genes and was downregulated in WG-59 cells following treatment with different losartan concentrations, when compared to untreated WG-59 cells.

  18. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves.

    Science.gov (United States)

    Jiao, Jiao; Xiong, Wei; Wang, Lunchang; Yang, Jiong; Qiu, Ping; Hirai, Hiroyuki; Shao, Lina; Milewicz, Dianna; Chen, Y Eugene; Yang, Bo

    2016-08-01

    Individuals with bicuspid aortic valves (BAV) are at a higher risk of developing thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV). The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest (NC) and paraxial mesoderm (PM), respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs)-derived SMCs but not paraxial mesoderm cells (PMCs)-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs) from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11) and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  19. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

    Directory of Open Access Journals (Sweden)

    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  20. A potential inhibitor of rat aortic vascular smooth muscle cell proliferation from the pollen of Typha angustata.

    Science.gov (United States)

    Nhiem, Nguyen Xuan; Kiem, Phan Van; Minh, Chau Van; Lee, Jung-Jin; Ku, Ja Hyeong; Myung, Chang-Seon; Kim, Young Ho

    2010-12-01

    By various chromatographic methods, three flavonoids, (2S)-naringenin (1), isorhamnetin 3-O-(2-O-α-L-rhamnopyranosyl) β-D-glucopyranoside (2), typhaneoside (3), and two sterol glycosides, β-sitosterol-3-O-(6-octadecanoyl) β-D-glucopyranoside (4) and β-sitosterol-3-O-(6-octadeca-9Z,12Z-dienoyl) β-D-glucopyranoside (5), were isolated from the pollen of Typha angustata. Their structures were determined on the basis of spectroscopic analyses. The flavonoids (1-3) were evaluated for their effects on the viability and proliferation of rat aortic smooth muscle cells. (2S)-naringenin (1) significantly inhibited cell proliferation in a dose-dependent manner without cytotoxic at concentrations of 30, and 50 μM; it reduced the number of cells following PDGF-BB treatment to 1.83 ± 0.30 × 10(4) and 2.20 ± 0.60 × 10(4) cells/well, respectively. These findings suggest that (2S)-naringenin has antiproliferative effects on aortic smooth muscle cells.

  1. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Yan TAN; Qiang TANG; Ben-rong HU; Ji-zhou XIANG

    2007-01-01

    Aim: To investigate the antioxidant properties of berberine (Ber) on corpus cavenosum smooth muscle cells (CCSMC) in penile erectile dysfunction. Methods: We examined the effects of Ber on cultured rabbit CCSMC damaged by hydrogen peroxide (H2O2) through examining cell viability by methyl thiazolyl tetrazolium assay and assessing the level of malondialdehyde (MDA), superoxide dismutase (SOD) activity, nitric oxide (NO) products, and lactate dehydrogenase (LDH) re- lease in cells after stimulation with H202. Results: Treatment with 1 mmol/L H2O2 significantly decreased the cell viability, NO products, and SOD activity of CCSMC from 100% to 48.57%+4.1% (P<0.01), 66.8±16.3 to 6.7±2.1 μmol/L (P<0.01), and 49.5±1.8 to 30.1±2.6 U/mL (P<0.01), respectively, and increased LDH release and MDA content from 497.6±69.5 to 1100.5±56.3 U/L (P<0.01) and 3.7±1.3 to 78.4±2.9 nmol/mg protein (P<0.01), respectively. However, treatment with different con- centrations of Ber (10-1000 μmol/L) inhibited the damaging effects of H2O2, with increased cell viability (P<0.05 or P<0.01), NO production (P<0.01), and SOD activity (P<0.01) and decreased LDH release and MDA content (both P<0.01). Conclusion: Bet could produce its antioxidant action on oxidative stress-induced cultured CCSMC. These effects may be of benefit in the prevention of penile erectile dysfunction.

  2. EFFECT OF STENT ABSORBED c-myc ANTISENSE OLIGODEOXYNUCLEOTIDE ON SMOOTH MUSCLE CELLS APOPTOSIS IN RABBIT CAROTID ARTERY

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 李江; 崔翰斌; 徐仓宝; 朱参战

    2002-01-01

    Objective To investigate the effect of gelatin coated Platinium-Iridium stent absorbed c-myc antisense oligodeoxynucleotide (ASODN) on smooth muscle cells apoptosis in a normal rabbit carotid arteries. Methods Gelatin coated Platinium-Iridium stents were implanted in the right carotid arteries of 32 rabbits under vision. Animals were randomly divided into control group and treated group receiving c-myc ASODN (n=16, respectively). On 7, 14, 30 and 90 days following the stenting procedure ,morphometry for caculation of neointimal area and mean neointimal thickness were performed.The expression of c-myc protein was detected by immunohistochemical method. Apoptotic smooth muscle cells was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Results At 7 and 14 days after stenting,there were no detectable apoptotic cells in both groups. The apoptotic cells occurred in the neointima 30 and 90 days after stenting, and the number of apoptotic cells at 30 days were less [4.50±1.29 vs 25.75±1.89 (number/0.1mm2)] than that at 90 days [13.50±1.91 vs 41.50±6.46 (number/0.1mm2)]. Meanwhile c-myc ASODN induced more apoptotic cells than the control group(P<0.0001). c-myc protein expression was weak positive or negative in treated group and positive in control group.Conclusion c-myc ASODN can induce smooth muscle cells apoptosis after stenting in normal rabbit carotid arteries,and it can be used to prevent in-stent restenosis.

  3. The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants.

    Science.gov (United States)

    Sinha, Indranil; Hannawa, Kevin K; Ailawadi, Gorav; Woodrum, Derek T; Ford, John W; Henke, Peter K; Stanley, James C; Eagleton, Matthew J; Upchurch, Gilbert R

    2006-01-01

    Our objective was to examine the role of an exogenous nitric oxide (NO) donor, DETA-NONOate (DETA), on matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 expression and activity in interleukin (IL)-1beta-induced rat aortic smooth muscle cells (RA-SMCs) and rat aortic explants (RAEs). RA-SMCs were incubated with IL-1beta (2 ng/ml), an inflammatory cytokine known to induce MMP-9 expression, and increasing concentrations of DETA (0, 1.0, 10, 100 microM; n = 3/group) for 48 hr. RAEs were incubated with IL-1beta (2 ng/mL) and increasing concentrations of DETA (0, 5.0, 50, 100, and 500 microM; n = 3/group) for 48 hr. Media were collected and assayed for NO(x) by the Griess reaction and MMP-9 activity by zymography. Messenger RNA (mRNA) was extracted from cells and analyzed for MMP-9, MMP-2, and TIMP-1 expression levels by quantitative real-time reverse-transcriptase polymerase chain reaction. All statistical analyses were performed by analysis of variance. In RA-SMCs and RAEs, DETA administration resulted in a dose-dependent increase in media NOx concentration (RA-SCM p < 0.01, RAE p < 0.01) and a concurrent decrease in both MMP-9 expression (RASMC p = 0.01, RAE p = 0.01) and activity (RASMC p = 0.04, RAE p = 0.006). There were no significant differences seen in MMP-2 and TIMP-1 expression or activity in response to DETA exposure. DETA decreased IL-1beta-induced MMP-9 expression and activity in both RA-SMCs and RAEs in a dose-dependent fashion. In addition, DETA administration had no effect on MMP-2 or TIMP-1 expression or activity in vitro. These data suggest that NO donors may be beneficial in decreasing MMP-9 levels and might serve to inhibit MMP-9-dependent vessel wall remodeling seen during abdominal aortic aneurysm formation.

  4. Relaxation of uterine and aortic smooth muscle by glaucolides D and E from Vernonia liatroides.

    Science.gov (United States)

    Campos, María; Oropeza, Martha; Ponce, Héctor; Fernández, Jaquelina; Jimenez-Estrada, Manuel; Torres, Héctor; Reyes-Chilpa, Ricardo

    2003-01-01

    Vernonia spp. (Asteraceae) are used in herbolaria in Latin America in menstrual and stomach disorders, suggesting smooth muscle relaxing properties of some of their chemical constituents. For pharmacological support for this belief, sesquiterpene lactones glaucolides D and E were assayed on isolated rat smooth muscle. Glaucolide E proved more potent than glaucolide D to relax high KCl- or noradrenaline-induced contractions in aorta and to relax the high KCl-contraction in uterus. Hirsutinolide-type sesquiterpene lactone also was tested but displayed no effect. Relaxation of smooth muscle by structurally related sesquiterpene lactone parthenolide has been attributed mainly to the alpha-methylene gamma-lactone moiety; because glaucolides D and E lack this functional group, their relaxant properties may rely on other alkylating sites such as C10 of the germacra-1(10),4-diene-4-epoxide skeleton.

  5. A monovalent ion-selective cation current activated by noradrenaline in smooth muscle cells of rabbit ear artery.

    Science.gov (United States)

    Wang, Q; Hogg, R C; Large, W A

    1993-04-01

    Membrane currents were recorded with the perforated-patch method with a low-chloride (35 mM) pipette solution in isolated smooth muscle cells of the rabbit ear artery. At a holding potential of -50 mV in potassium-free conditions spontaneous inward single-channel currents were observed and noradrenaline evoked a noisy inward current, which appeared to be comprised of the spontaneous currents. The reversal potential (Vr) of the spontaneous channel and noradrenaline-induced current was not affected in anion-substitution experiments but Vr was altered when external Na+ was replaced with choline or TRIS. The relationship between clamp potential and spontaneous single-channel current amplitude was linear and the mean unitary conductance was 28 pS. Caffeine, which releases calcium from the sarcoplasmic reticulum, and the calcium ionophore ionomycin activated the cation current and also blocked the response to noradrenaline. Spontaneous channel current activity and the noradrenaline-induced current were blocked when external NaCl was replaced with 89 mM CaCl2. The response to noradrenaline was blocked by prazosin but was not affected by yohimbine and therefore the response is mediated by alpha 1-adrenoceptors. It is concluded that in rabbit ear artery smooth muscle cells there is a calcium-activated cation channel of 28 pS conductance, which is relatively impermeable to calcium but can be activated by noradrenaline.

  6. Metformin inhibits vascular calcification in female rat aortic smooth muscle cells via the AMPK-eNOS-NO pathway.

    Science.gov (United States)

    Cao, Xiaorui; Li, Huan; Tao, Huiren; Wu, Ning; Yu, Lifeng; Zhang, Dawei; Lu, Xiaozhao; Zhu, Jinyu; Lu, Zifan; Zhu, Qingsheng

    2013-10-01

    Metformin exhibits diverse protective effects against diabetic complications, such as bone loss. Here, we investigated the effect of metformin on vascular calcification, another type 2 diabetes complication. In female rat aortic smooth muscle cells (RASMCs), we observed that metformin significantly alleviated β-glycerophosphate-induced Ca deposition and alkaline phosphatase activity, corresponding with reduced expression of some specific genes in osteoblast-like cells, including Runx2 and bone morphogenetic protein-2, and positive effects on α-actin expression, a specific marker of smooth muscle cells. Mechanistic analysis showed that phosphorylation levels of both AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were increased with NO overproduction. After inhibition of either AMPK or eNOS with the pharmacologic inhibitors, compound C or Nω-Nitro-L-arginine methyl ester, NO production was lowered and metformin-meditated vascular protection against β-glycerophosphate-induced Ca deposition was removed. Our results support that metformin prevents vascular calcification via AMPK-eNOS-NO pathway.

  7. Evaluation of Ceftobiprole in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

    OpenAIRE

    2005-01-01

    Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and is active against methicillin- and vancomycin-resistant Staphylococcus aureus. Ceftobiprole was compared to vancomycin in a rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were equally effective against endocarditis caused by methicillin-resistant S. aureus strain 76, whereas ceftobipro...

  8. Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein.

    Science.gov (United States)

    Ngo, Doan T M; Stafford, Irene; Kelly, Darren J; Sverdlov, Aaron L; Wuttke, Ronald D; Weedon, Helen; Nightingale, Angus K; Rosenkranz, Anke C; Smith, Malcolm D; Chirkov, Yuliy Y; Kennedy, Jennifer A; Horowitz, John D

    2008-08-20

    Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D(2) and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D(2) supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D(2) alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D(2) treated rabbits developed AVS with increased AV(BS) (17.6+/-1.4 dB vs 6.7+/-0.8 dB, Pvitamin D(2) induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.

  9. 2-Methoxycinnamaldehyde inhibits the TNF-α-induced proliferation and migration of human aortic smooth muscle cells.

    Science.gov (United States)

    Jin, Young-Hee; Kim, Soo-A

    2017-01-01

    The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a crucial event in the development of atherosclerosis, and tumor necrosis factor-α (TNF-α) is actively involved in this process by enhancing the proliferation and migration of VSMCs. 2-Methoxycinnamaldehyde (MCA) is a natural compound of Cinnamomum cassia. Although 2-hydroxycinnamaldehyde (HCA), another compound from Cinnamomum cassia, has been widely studied with regard to its antitumor activity, MCA has not attracted researchers' interest due to its mild toxic effects on cancer cells and its mechanisms of action remain unknown. In this study, we examined the effects of MCA on the TNF-α-induced proliferation and migration of human aortic smooth muscle cells (HASMCs). As shown by our results, MCA inhibited TNF-α-induced cell proliferation by reducing the levels of cyclin D1, cyclin D3, CDK4 and CDK6, and increasing the levels of the cyclin-dependent kinase inhibitors, p21 and p27, without resulting in cellular cytotoxicity. Furthermore, MCA decreased the level of secreted matrix metalloproteinase (MMP)-9 by inhibiting MMP-9 transcription. Unexpectedly, MCA did not affect the TNF-α-induced levels of mitogen-activated protein kinases (MAPKs). However, by showing that MCA potently inhibited the degradation of IκBα and the subsequent nuclear translocation of nuclear factor-κB (NF-κB), we demonstrated that MCA exerts its effects through the NF-κB signaling pathway. MCA also effectively inhibited platelet-derived growth factor (PDGF)-induced HASMC migration. Taken together, these observations suggest that MCA has the potential for use as an anti-atherosclerotic agent.

  10. Mechanical stretch modulates microRNA 21 expression, participating in proliferation and apoptosis in cultured human aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Jian tao Song

    Full Text Available OBJECTIVES: Stretch affects vascular smooth muscle cell proliferation and apoptosis, and several responsible genes have been proposed. We tested whether the expression of microRNA 21 (miR-21 is modulated by stretch and is involved in stretch-induced proliferation and apoptosis of human aortic smooth muscle cells (HASMCs. METHODS AND RESULTS: RT-PCR revealed that elevated stretch (16% elongation, 1 Hz increased miR-21 expression in cultured HASMCs, and moderate stretch (10% elongation, 1 Hz decreased the expression. BrdU incorporation assay and cell counting showed miR-21 involved in the proliferation of HASMCs mediated by stretch, likely by regulating the expression of p27 and phosphorylated retinoblastoma protein (p-Rb. FACS analysis revealed that the complex of miR-21 and programmed cell death protein 4 (PDCD4 participated in regulating apoptosis with stretch. Stretch increased the expression of primary miR-21 and pre-miR-21 in HASMCs. Electrophoretic mobility shift assay (EMSA demonstrated that stretch increased NF-κB and AP-1 activities in HASMCs, and blockade of AP-1 activity by c-jun siRNA significantly suppressed stretch-induced miR-21 expression. CONCLUSIONS: Cyclic stretch modulates miR-21 expression in cultured HASMCs, and miR-21 plays important roles in regulating proliferation and apoptosis mediated by stretch. Stretch upregulates miR-21 expression at least in part at the transcription level and AP-1 is essential for stretch-induced miR-21 expression.

  11. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

    Indian Academy of Sciences (India)

    HAN SOL KIM; HONGLIANG LI; HYE WON KIM; SUNG EUN SHIN; IL-WHAN CHOI; AMY L FIRTH; HYOWEON BANG; YOUNG MIN BAE; WON SUN PARK

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv)channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertralinedecreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 μM and a slope value (Hillcoefficient) of 0.61. Although the application of 1 μM sertraline did not affect the steady-state activation curves,sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine,had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From theseresults, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptakeinhibition by shifting inactivation curves to a more negative potential.

  12. Effects of flavone on the contractile activity of the circular smooth muscle of the rabbit middle colon in vitro.

    Science.gov (United States)

    Benabdallah, Hassiba; Gharzouli, Kamel

    2015-08-05

    The circular smooth muscles of the middle colon of the rabbit generate giant contractions of high amplitude and low frequency. Flavone, at various concentrations, reduces the giant contractions and the tonic contraction induced by 10 µM carbachol and 80 mM KCl. The contractions induced by dequalinium and tetraethylammonium are reduced by flavone (30 µM). At 100 µM, flavone decreases the contraction induced by 100 µM methylene blue and 1mM orthovanadate. These results suggest that flavone inhibit the giant contractions by (1) inhibition of voltage-dependent Ca(2+) channels, (2) activation of guanyl cyclase, (3) opening of K(+) channels and (4) inhibition of tyrosines kinases.

  13. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Choi, Il-Whan; Firth, Amy L; Bang, Hyoweon; Bae, Young Min; Park, Won Sun

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertraline decreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 mu M and a slope value (Hill coefficient) of 0.61. Although the application of 1 mu M sertraline did not affect the steady-state activation curves, sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine, had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From these results, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptake inhibition by shifting inactivation curves to a more negative potential.

  14. Proliferation and C-myc Gene Expression of Smooth Muscle Cells in Rabbit Carotid Artery after Stenting

    Institute of Scientific and Technical Information of China (English)

    张新霞; 崔长琮; 胡雪松; 魏文斌; 李松; 许香广

    2004-01-01

    Objectives To investigate the proliferation of smooth muscle cells (VSMCs) and the expression of c-myc gene in rabbit carotid arteries after stenting. Methods Platinium-Iridium stent were implanted into the right carotid arteries of 16 rabbits under vision. 7,14,30 and 90 days after the stenting procedure, morphological changes of VSMCs were observed under light and transmission electron microscope. The c-myc gene expression was detected by in situ hybridization (ISH) and immunohistochemical staining. Results 7 days after stenting, the phenotype of VSMCs changed from contractile to synthetic phenotype; there were a number of proliferative VSMCs in the neointima. At 14 and 30 days, there were synthetic and transitive VSMCs. At 90 days, the phenotype of VSMCs recovered to contractile phenotype.The ultrastructure of typical synthetic phenotype of VSMCs were round, containing a large amount of rough endoplasmic reticulum and mitochondria. Cmyc expression were positive both by ISH and immunohistochemical staining. Conclusions C-myc gene expression increases and closely relates to VSMCs proliferation after stenting. It may play an important role in the in-stent restenosis.

  15. Potential role of vascular smooth muscle cell-like progenitor cell therapy in the suppression of experimental abdominal aortic aneurysms.

    Science.gov (United States)

    Park, Hyung Sub; Choi, Geum Hee; Hahn, Soli; Yoo, Young Sun; Lee, Ji Youl; Lee, Taeseung

    2013-02-08

    Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.

  16. Evaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols.

    Science.gov (United States)

    Adiguzel, Zelal; Arda, Nazli; Kacar, Omer; Serhatli, Muge; Gezer Tas, Serpil; Baykal, Ahmet Tarik; Baysal, Kemal; Acilan, Ceyda

    2014-12-01

    Oxysterols, oxygenated derivatives of cholesterol, are found abundantly in the plasma and atherosclerotic plaques, a common risk factor for thoracic aortic aneurysms (TAAs). Among the oxysterols, namely 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC), lead both to induction of reactive oxygen species (ROS) in cells and to apoptosis in smooth muscle cells (SMCs) probably due to increased oxidative stress. Since loss of SMCs through apoptosis is a major event in TAA formation, it is important to understand the molecular pathways of apoptosis in response to ROS in TAAs. Very little is known about the effect of oxysterols on TAA SMCs. Therefore, we investigated molecular pathways participating in the oxysterol induced cell death of TAAs. Our results showed that TAA SMCs died mainly as a result of apoptosis as suggested by cellular shrinkage, blebbing, DNA condensation/fragmentation in response to oxysterol treatment. There was no significant difference in oxysterol induced cell death between TAA and control SMCs. Addition of antioxidant molecules prevented cell death, hence ROS appears to be involved in the apoptosis of these cells. While oxysterol treatment increased caspase 3 activity, cell death was not rescued in its absence. Efficient silencing of other targets including apoptotic proteins (p53, Bax), and survival proteins (Akt1, Akt2) showed that apoptosis can occur through p53, and Bax independent pathways. Silencing Akt1 or Akt2 did not lead to further cell death. These results indicate that oxysterols can induce several cell death pathways in TAA SMCs.

  17. Shikonin inhibits TNF-α-induced growth and invasion of rat aortic vascular smooth muscle cells.

    Science.gov (United States)

    Zhang, Xuemin; Hu, Wenyu; Wu, Fang; Yuan, Xue; Hu, Jian

    2015-08-01

    Shikonin is a naphthoquinone compound extracted from the Chinese herb purple gromwell. Shikonin has broad antibacterial, anti-inflammatory, and antitumor activities. The tumor necrosis factor-α (TNF-α)-induced proliferation and invasion of vascular smooth muscle cells (VSMCs) is an important factor that contributes to atherosclerosis. The effects of shikonin on the proliferation and apoptosis of VSMCs have been reported; however, the function of shikonin on TNF-α-mediated growth and invasion of VSMCs during atherosclerosis remains unclear. In this study, we used Western blot, flow cytometry, real-time quantitative PCR, and enzyme-linked immunosorbent assay to investigate the effect of shikonin on the TNF-α-induced growth and invasion of VSMCs and to determine the underlying mechanism. Our results showed that shikonin inhibits the TNF-α-mediated growth and invasion. Further study revealed that shikonin regulates the activation of nuclear factor kappa B and phosphatidyl inositol 3-kinase signaling pathways; modulates the expression of cyclin D1, cyclin E, B-cell lymphoma 2, and Bax; activates caspase-3 and caspase-9; induces cell cycle arrest; and promotes the apoptosis of VSMCs. Together, our results indicate that shikonin may become a promising agent for the treatment of atherosclerosis and they also establish foundation for the development of anti-atherosclerosis drugs.

  18. Mechanical Anisotropy of Rat Aortic Smooth Muscle Cells Decreases with Their Contraction

    Science.gov (United States)

    Nagayama, Kazuaki; Matsumoto, Takeo

    Tensile properties of smooth muscle cells freshly isolated from rat thoracic aortas (FSMCs) in their major and minor axes were measured using a laboratory-made micro tensile tester. The relationship between the tension applied to a cell and its elongation was obtained in untreated cells and those treated with 10-5M serotonin to induce contraction. An initial stiffness of untreated FSMCs, normalized by their initial cross-sectional area perpendicular to the stretch direction, was significantly higher in the major axis (14.8±4.3kPa, mean±SEM, n=5) than the minor axis (2.8±1.0kPa, n=5). The stiffness increased significantly in response to the contraction, but the increase was much higher in the minor axis (59.0±9.4kPa, n=4) than in the major (88.1±13.3kPa, n=4). The difference between the two directions was insignificant in the contracted state. Observations of the morphology of actin filaments with a confocal laser scanning microscope in untreated FSMCs revealed that they were long fibers running almost parallel to the major axis, while those in contracted cells showed an aggregated structure without a preferential direction. These results may indicate that anisotropy in untreated FSMCs is caused by the anisotropic alignment of their actin filaments, and that such anisotropy disappears in response to actin filament reorganization caused by the contraction.

  19. Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells.

    Science.gov (United States)

    Mras, S; Sperelakis, N

    1981-04-24

    Reaggregate cultures (primary) were prepared from enzyme-dispersed vascular smooth muscle (VSM) cells from rat aortas. The cultures were incubated for 7-10 days, and then studied by the intracellular microelectrode technique. The cells were electrically quiescent (mean resting potential of --47 mV), and extracellular electrical stimulation usually did not elicit a membrane response. Addition of 10 mM tetraethylammonium rapidly induced excitability, allowing the VSM cells to fire Ca2+-dependent action potentials in response to electrical stimulation. The electrical responses often had two components, an initial spike and a later plateau-like component. The action potential spikes had a mean amplitude of 22 mV but occasionally were overshooting; the plateaus had a mean duration (at 50% repolarization) of 3.8 sec. A new anti-anginal agent, bepridil (10(-8)-10(-5) M), depressed the amplitude and duration of the plateau and blocked the spike component of the action potential in a dose-dependent fashion without affecting the resting potential. This finding is consistent with the view that bepridil acts as a Ca2+-antagonistic agent to prevent the generation of the action potentials, and this action can explain its antianginal properties.

  20. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Edvinsson Lars

    2009-07-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a potent vasoactive peptide, which induces vasoconstriction and proliferation in vascular smooth muscle cells (VSMCs through activation of endothelin type A (ETA and type B (ETB receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2 mitogen-activated protein kinases (MAPK are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation of ERK1/2 as a functional signal molecule for endothelin receptor activity. Results Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 μM. The activation of ERK1/2 was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETA antagonist BQ123 blocked the ET-1 effect, while the ETB antagonist BQ788 had no significant effect. However, a selective ETB receptor agonist, Sarafotoxin 6c (S6c caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 μM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123 or the combined use of BQ123 and BQ788. To further explore ET-1 intracellular signaling, PKC inhibitors (staurosporin and GF109203X, PKC-delta inhibitor (rottlerin, PKA inhibitor (H-89, and phosphatidylinositol 3-kinase (PI3K inhibitor (wortmannin were applied. The inhibitors showed significant inhibitory effects on ET-1

  1. Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hung-hsing CHAO; Ju-chi LIU; Jia-wei LIN; Cheng-hsien CHEN; Chieh-hsi WU; Tzu-hurng CHENG

    2008-01-01

    Aim: Recent experimental and human studies have shown that hyperuricemia is associated with hypertension and cardiovascular diseases. Elevated levels of endotheliu-1 (ET-1) has been regarded as one of the most powerful indepen-dent predictors of cardiovascular diseases. For investigating whether uric acidinduced vascular diseases are related to ET-1, the uric acid-induced ET-1 expression in human aortic smooth muscle cells (HASMC) was examined. Methods: Cultured HASMC treated with uric acid, cell proliferation and ET-1 expression were examined. Antioxidant pretreatments on uric acid-induced extracellular signal-regulated kinases (ERK) phosphorylation were carried out to elucidate the redox-sensitive pathway in proliferation and ET-1 gene expression. Results: Uric acid was found to increase HASMC proliferation, ET-1 expression and reactive oxygen species production. The ability of both N-acetylcysteine and apocynin (1-[4-hydroxy-3-methoxyphenyl]ethanone, a NADPH oxidase inhibitor) to inhibit uric acid-induced ET-1 secretion and cell proliferation suggested the involvement of intracellular redox pathways. Furthermore, apocynin, and p47phox small interfering RNA knockdown inhibited ET-1 secretion and cell proliferation induced by uric acid. Inhibition of ERK by U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene) significantly suppressed uric acid-induced ET-I expression, implicating this pathway in the response to uric acid. In addition, uric acid increased the transcription factor activator protein-1 (AP-1) medi-ated reporter activity, as well as the ERK phosphorylation. Mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. Conclusion: This is the first observation of ET-1 regulation by uric acid in HASMC, which implicates the important role of uric acid in the vascular changes associated with hypertension and vascular diseases.

  2. Prostacyclin production in rat aortic smooth muscle cells: role of protein kinase C, phospholipase D and cyclooxygenase-2 expression.

    Science.gov (United States)

    Frias, Miguel A; Dubouloz, Frédérique; Rebsamen, Michela C; Lang, Ursula

    2003-11-01

    The present study was designed to investigate the role of protein kinase C (PKC) and phospholipase D (PLD) in angiotensin II (AngII)- and phorbol ester (PMA)-induced cyclooxygenase-2 (COX-2) expression and prostacyclin (PGI(2)) production in rat aortic smooth muscle cells (VSMC). Prostacyclin production in cultured VSMC was determined by radioimmunoassay. PKC activity was examined by measuring the transfer of 32P from (gamma-32P)ATP to histone III-S. COX-2 expression was determined by Western blotting. To measure PLD activity, thin layer chromatography was used. AngII (50 nM) and PMA (100 nM) promoted the translocation of PKC activity from the cytosol to the membranes within 30 min, followed by a strong increase in PLD activity as well as COX-2 expression and PGI(2) production. After 48 h exposure to PMA, PKC was downregulated resulting in a complete suppression of its activity. PKC-downregulation and the PKC inhibitor CGP41251 abolished PMA- and AngII-induced PLD activation, suppressed the stimulatory effect of PMA on COX-2 expression and PGI(2) production and strongly inhibited that of AngII. Furthermore, AngII- and PMA-induced PGI(2) production depended on protein synthesis and COX-2 but not COX-1 activity. Inhibition of PLD-mediated phosphatidic acid (PA) formation by 1% 1-butanol abolished AngII-induced COX-2 expression and PGI(2) secretion, while dioctanoyl PA increased COX-2 expression and PGI(2) production in a time- and concentration-dependent manner. Our results indicate that in VSMC, AngII promotes PGI(2) production to a large extent through a rise in COX-2 expression which is mediated by PA generated from increased PKC-dependent PLD activity.

  3. Rock Tea extract (Jasonia glutinosa) relaxes rat aortic smooth muscle by inhibition of L-type Ca(2+) channels.

    Science.gov (United States)

    Valero, Marta Sofía; Oliván-Viguera, Aida; Garrido, Irene; Langa, Elisa; Berzosa, César; López, Víctor; Gómez-Rincón, Carlota; Murillo, María Divina; Köhler, Ralf

    2015-12-01

    In traditional herbal medicine, Rock Tea (Jasonia glutinosa) is known for its prophylactic and therapeutic value in various disorders including arterial hypertension. However, the mechanism by which Rock Tea exerts blood pressure-lowering actions has not been elucidated yet. Our aim was to demonstrate vasorelaxing effects of Rock Tea extract and to reveal its possible action mechanism. Isometric myography was conducted on high-K+-precontracted rings from rat thoracic aorta and tested extracts at concentrations of 0.5-5 mg/ml. Whole-cell patch-clamp experiments were performed in rat aortic vascular smooth muscle cells (line A7r5) to determine blocking effects on L-type Ca(2+) channels. Rock Tea extract relaxed the aorta contracted by high [K+] concentration dependently with an EC50 of ≈2.4 mg/ml and produced ≈75 % relaxation at the highest concentration tested. The L-type Ca(2+) channel blocker, verapamil (10(-6) M), had similar effects. Rock Tea extract had no effect in nominally Ca(2+)-free high-K(+) buffer but significantly inhibited contractions to re-addition of Ca(2+). Rock Tea extract inhibited the contractions induced by the L-type Ca(2+) channel activator Bay K 8644 (10(-5) M) and by phenylephrine (10(-6) M). Rock Tea extract and Y-27632 (10(-6) M), Rho-kinase inhibitor, had similar effects and the respective effects were not additive. Patch-clamp experiments demonstrated that Rock Tea extract (2.5 mg/ml) virtually abolished L-type Ca(2+) currents in A7r5. We conclude that Rock Tea extract produced vasorelaxation of rat aorta and that this relaxant effect is mediated by inhibition of L-type Ca(2+) channels. Rock Tea extracts may be of phytomedicinal value for prevention and adjuvant treatment of hypertension and other cardiovascular diseases.

  4. Effects of pinacidil on proliferation of cultured rabbit airway smooth muscle cells induced by endothelin-1

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; XIE Wei-ping; QI Xu; ZHANG Xi-long

    2005-01-01

    @@ It has been found that the potassium channel dysfunction of the membrane of airway smooth muscle cells (ASMCs) is closely associated with proliferation of ASMCs.1 Preliminary research has demonstrated that pinacidil, an ATP sensitive potassium channel (KATP) opener, could play a remarkable role in the prevention and treatment of antigen induced bronchial asthma in guinea pigs.2 This study was designed to investigate further the role and molecular mechanism of the proliferation of ASMCs: a chief pathological change of the nonacute phase of bronchial asthmatic episodes.

  5. The cardiac sodium current Na(v)1.5 is functionally expressed in rabbit bronchial smooth muscle cells.

    Science.gov (United States)

    Bradley, E; Webb, T I; Hollywood, M A; Sergeant, G P; McHale, N G; Thornbury, K D

    2013-08-15

    A collagenase-proteinase mixture was used to isolate airway smooth muscle cells (ASMC) from rabbit bronchi, and membrane currents were recorded using the whole cell patch-clamp technique. Stepping from -100 mV to a test potential of -40 mV evoked a fast voltage-dependent Na(+) current, sometimes with an amplitude of several nanoamperes. The current disappeared within 15 min of exposure to papain + DTT (n = 6). Comparison of the current in ASMC with current mediated by NaV1.5 α-subunits expressed in human embryonic kidney cells revealed similar voltage dependences of activation (V1/2 = -42 mV for NaV1.5) and sensitivities to TTX (IC50 = 1.1 and 1.2 μM for ASMC and NaV1.5, respectively). The current in ASMC was also blocked by lidocaine (IC50 = 160 μM). Although veratridine, an agonist of voltage-gated Na(+) channels, reduced the peak current by 33%, it slowed inactivation, resulting in a fourfold increase in sustained current (measured at 25 ms after onset). In current-clamp mode, veratridine prolonged evoked action potentials from 37 ± 9 to 1,053 ± 410 ms (n = 8). Primers for NaV1.2-1.9 were used to amplify mRNA from groups of ∼20 isolated ASMC and from whole bronchial tissue by RT-PCR. Transcripts for NaV1.2, NaV1.3, and NaV1.5-1.9 were detected in whole tissue, but only NaV1.2 and NaV1.5 were detected in single cells. We conclude that freshly dispersed rabbit ASMC express a fast voltage-gated Na(+) current that is mediated mainly by the NaV1.5 subtype.

  6. Evaluation of ceftobiprole in a rabbit model of aortic valve endocarditis due to methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.

    Science.gov (United States)

    Chambers, Henry F

    2005-03-01

    Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and is active against methicillin- and vancomycin-resistant Staphylococcus aureus. Ceftobiprole was compared to vancomycin in a rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were equally effective against endocarditis caused by methicillin-resistant S. aureus strain 76, whereas ceftobiprole was more effective than vancomycin against the vancomycin-intermediate S. aureus strain HIP5836. The activity of ceftobiprole against drug-resistant strains of S. aureus warrants its further clinical development.

  7. Inhibition Mechanism of Emodin on Rabbit Vascular Smooth Muscle Cells Proliferation

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of atherosclerosis and restenosis after angioplasty and vein graft.In this study, MTT colormetry was used to test the effective scope of emodin to inhibit VSMCs proliferation.Flow cytometry and confocal image were adopted to investigate its inhibitive mechanism.The results show that emodin could inhibit the growth and proliferation of VSMCs and the inhibition rate of emodin on VSMCs is 24.6%-94.58%, which is time - and concentration - dependent.Emodin could reduce S phase entry, increase the apoptosis of VSMCs, and reduce the intensity of[Ca2+]i in hPDGF B/B stimulated VSMCs.This research provides theoretical basis for medical application of emodin.It is concluded that emodin could inhibit the growth and proliferation of VSMCs effectively.Decreasing the DNA synthesis, increasing the cell apoptosis and reducing the intensity of[Ca2+]i in hPDGF B/B stimulated VSMCs may be the inhibitive mechanism of emodin against VSMCs proliferation.

  8. EFFECTS OF OUABAIN AND DIGOXIN ON THE GENE EXPRESSION OF SODIUM PUMP α-SUBUNIT ISOFORM IN AORTIC SMOOTH MUSCLE OF RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To compare the effects of ouabain and digoxin on both the systolic blood pressure and sodium pump α-subunit isoforms gene expression in the aortic smooth muscle of rats. Methods Normal SpragueDawley rats were injected with ouabain (20μg·kg-1 ·d-1 ,i. p),digoxin (32 μg·kg-1 ·d-1,i. p)and normal saline once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later,all the rats were killed and sodium pump α1-,α2-,and α3-subunit mRNA levels were detected in the aortic smooth muscle with reverse transcription polymerase chain reaction(RT-PCR) method. Results The systolic blood pressure of rats infused with ouabain increased significantly at the end of week 6 [132. 6± 9. 0 mmHg (1 mmHg = 0. 133 kPa)vs 115. 7±8.2mmHg, P <0. 01] ,while no difference of blood pressure was found between digoxin group and NS group (P>0.05).The expression of sodium pump α-subunit isoforms in aortic smooth muscle was regulated by either ouabain or digoxin:both ouabain and digoxin increased α1- and α3-subunit expression, α2-subunit decreased in digoxin group but unchanged in ouabain group. Conclusion These results suggest that both ouabain and digoxin could regulate sodium pump α-subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and might be responsible for the difference between the pharmacological and toxicological effects of ouabain and digoxin,including their effects on blood pressure.

  9. The effects of low density lipoproteins modified by incubation with chondroitin 6-sulfate on human aortic smooth muscle cells.

    Science.gov (United States)

    Tîrziu, D; Jinga, V V; Serban, G; Simionescu, M

    1999-11-01

    One of the first changes that take place within the artery intima at the inception of atherosclerosis is the accumulation of LDL-derived modified lipoproteins which appear as subendothelial lipid droplets and vesicles. With time, the LDL retention and interaction with intimal chondroitin sulfate-proteoglycans may induce further structural and functional modification of the lipoproteins. The aim of this study was to produce 'in vitro' modified lipoproteins by LDL incubation with chondroitin 6-sulfate (CS, at 37 degrees C, for 48 h, in the absence of antioxidants) and to test their effects on cultured human aortic smooth muscle cells (SMCs). CS induced LDL modification (CS-mLDL) consisted in formation of a mixture of fused particles (up to 150 nm diameter) and monomers with a small content of lipid peroxides and a partially degraded apo B-100, corresponding to a mild oxidation. Upon incubation with SMCs, CS-mLDL produced a concentration-dependent stimulation of 3H-thymidine incorporation, that, at low concentration (25 microg/ml), was 2-3-fold higher than that obtained when native LDL was used; this increase correlates well with the level of CS-mLDL uptake at the same concentration. Besides the mitogenic effect, CS-mLDL induced a significant stimulation of SMCs migration, comparable with that reported for oxidized LDL. Upon incubation with CS-mLDL, SMCs accumulated lipid droplets of various number and dimension, as revealed by Nile red staining and electron microscopy. Competition studies performed in the presence of 20-fold excess of native LDL and acetyl LDL showed that 125I-CS-mLDL were taken up both by LDL receptor and scavenger receptor. At high concentration (200 microg/ml), CS-mLDL had a cytotoxic effect that was not significantly different from that of native LDL. Together these results provide evidence of (i) the direct alteration produced by CS on LDL and (ii) the effect of CS-mLDL on SMCs migration, proliferation and transformation in lipid-laden cells

  10. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Institute of Scientific and Technical Information of China (English)

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

  11. In-vitro effects of PDE5 inhibitor and statin treatment on the contractile responses of experimental MetS rabbit's cavernous smooth muscle

    Directory of Open Access Journals (Sweden)

    Yasin Erden

    2014-03-01

    Full Text Available Objective: Hypercholesterolaemia promotes erectile dysfunction through increased superoxide formation and decreased nitric oxide bioactivity in cavernosal tissue. The role of nitric oxide on erectile function is well known. Statins have lipid lowering properties and can modulate endothelial nitric oxide bioavailability. Sildenafil, enhances smooth muscle relaxation in corpus cavernosum. We invastigated in-vitro effects of sildenafil and rosuvastatin on nonadrenergic, non-cholinergic and nitric oxide mediated cavernosal smooth musle relaxation in metabolic syndrome rabbits, since alterations in this pathway are recognised in diabetic and hypercholesterolemic erectile dysfunction. Methods: Ten male rabbits were fed a standart diet as control group, fourty male rabbits were fed a hypercholesterolemic diet for 12 weeks. Hypercholesterolemic group were divided for without treatment, rosuvastatin treatment, sildenafil teratment, and rosuvastatin + sildenafil treatment (N = 10 per groups. Results: Serum levels of cholesterol and glucose were significantly higher in the experimental group than in the control group (p < 0.05. After theraphy no differences were found among the groups in relaxation responses to sodium nitroprusside. The relaxation responses to carbachol and EFS were significantly reduced in metabolic syndrome group to control group (p < 0.05, but there were no differences between the other groups and control group. There was a significantly lower in-vitro relaxation response in the metabolic syndrome rabbits than in controls and the others (p < 0.05. Conclusion: Both agents improve in-vitro relaxation responses of erectile tissue from metabolic syndrome rabbits to endothelial non-adrenergic, non-cholinergic and nitric oxide. This finding supports to the results of other clinical studies with these drugs.

  12. miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.

    Science.gov (United States)

    Bi, Rui; Ding, Fangbao; He, Yi; Jiang, Lianyong; Jiang, Zhaolei; Mei, Ju; Liu, Hao

    2016-12-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR.

  13. Alterations of voltage-dependent calcium channel currents in basilar artery smooth muscle cells at early stage of subarachnoid hemorrhage in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Xianqing Shi

    Full Text Available OBJECTIVE: To investigate the changes in the currents of voltage-dependent calcium channels (VDCCs in smooth muscle cells of basilar artery in a rabbit model of subarachnoid hemorrhage (SAH. METHODS: New Zealand white rabbits were randomly divided into five groups: sham (C, normal (N, 24 hours (S1, 48 hours (S2 and 72 hours (S3 after SAH. Non-heparinized autologous arterial blood (1 ml/kg was injected into the cisterna magna to create SAH after intravenous anesthesia, and 1 ml/kg of saline was injected into cisterna magna in the sham group. Rabbits in group N received no injections. Basilar artery in S1, S2, S3 group were isolated at 24, 48, 72 hours after SAH. Basilar artery in group C was isolated at 72 hours after physiological saline injection. Basilar artery smooth muscle cells were isolated for all groups. Whole-cell patch-clamp technique was utilized to record cell membrane capacitance and VDCCs currents. The VDCCs antagonist nifedipine was added to the bath solution to block the Ca(++ channels currents. RESULTS: There were no significant differences in the number of cells isolated, the cell size and membrane capacitance among all the five groups. VDCC currents in the S1-S3 groups had higher amplitudes than those in control and sham groups. The significant change of current amplitude was observed at 72 hours after SAH, which was higher than those of 24 and 48 hours. The VDCCs were shown to expression in human artery smooth muscle cells. CONCLUSIONS: The changes of activation characteristics and voltage-current relationship at 72 hours after SAH might be an important event which leads to a series of molecular events in the microenvironment of the basilar artery smooth muscle cells. This may be the key time point for potential therapeutic intervention against subarachnoid hemorrhage.

  14. Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits.

    Science.gov (United States)

    Nie, Maoxiao; Yan, Yunfeng; Li, Xinhe; Feng, Tingting; Zhao, Xin; Zhang, Mingduo; Zhao, Quanming

    2016-01-01

    Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5-146.8%, and 241.5-255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate.

  15. Influence of Needling the Foot-Yangming Points on Intracellular Ca2+ Concentration in Smooth Muscles of the Gastric Antrum in Rabbits

    Institute of Scientific and Technical Information of China (English)

    Deng Yuanjiang; Yi Shouxiang; Lin Yaping; Yan Jie; Guo Hui; Xiang Zhiyong; Wu Fang; Liu Weiying; Chen Zhengqiu

    2007-01-01

    Objective: To investigate the influence of acupuncture at the points of Foot-Yangming Meridian on intracellular concentration of Ca2, called the 2nd messenger of gastric smooth muscles. Methods: 45rabbits were randomly divided into the following 5 groups: a normal saline group, a model group treated with atropine, an acupuncture group treated by needling the points of Foot-Yangming Meridian, an acupuncture group treated by needling the points of Foot-Shaoyang Meridian, an acupuncture group treated by needling the points of Foot-Taiyang Meridian, i.e. 9 rabbits in each group. After treatment, the smooth muscles of the gastric antrum were taken to make the suspension containing alive single muscular cells, and the intracellular calcium concentration ([Ca2+]i) was determined by a spectrofluorometer.Results: The concentration of [Ca2+]i in the group of Foot-Yangming Meridian was obviously higher than that of the atropine group (P<0.01), but with no significant differences found among all the other groups (P>0.05). Conclusion: The influence of acupuncture at the points of Foot-Yangming Meridian on gastric movement is related to the release of intracellular Ca2+ in the gastric smooth muscles.

  16. Depletion of endothelial or smooth muscle cell-specific angiotensin II type 1a receptors does not influence aortic aneurysms or atherosclerosis in LDL receptor deficient mice.

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    Debra L Rateri

    Full Text Available BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII induced atherosclerosis and abdominal aortic aneurysms (AAAs. However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs. METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with mice expressing Cre under the control of either Tie2 or SM22, respectively. Groups of males and females were fed a saturated fat-enriched diet for 3 months to determine effects on atherosclerosis. Deletion of AT1a receptors in either endothelial or smooth muscle cells had no discernible effect on the size of atherosclerotic lesions. We also determined the effect of cell-specific AT1a receptor deficiency on atherosclerosis and AAAs using male mice fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min. Again, deletion of AT1a receptors in either endothelial or smooth muscle cells had no discernible effects on either AngII-induced atherosclerotic lesions or AAAs. CONCLUSIONS: Although previous studies have demonstrated whole body AT1a receptor deficiency diminishes atherosclerosis and AAAs, depletion of AT1a receptors in either endothelial or smooth muscle cells did not affect either of these vascular pathologies.

  17. The effects of dehydroepiandrosterone (DHEA)/DHEA-sulfate (DHEAS) on the contraction responses of the clitoral cavernous smooth muscle from female rabbits.

    Science.gov (United States)

    Lee, Shin Young; Myung, Soon Chul; Lee, Moo Yeol; Kim, Tae Hyoung; Kim, Sae Chul; Kim, Kyung Do; Park, Soo Hyun; Kim, Won Yong

    2009-10-01

    Dehydroepiandrosterone (DHEA) is a multifunctional steroid that is increasingly available as a supplement aimed at improving libido and well-being in postmenopausal women in the recent times. Together with its sulfate version, DHEA-sulfate (DHEAS), it is the most abundant steroid in humans. The clitoris is an important component of the female sexual response, with its increased vascular response during sexual arousal that results in erection. To elucidate the direct effects of DHEA/DHEAS on the vasomotor reactivity of the rabbit clitoral cavernosum. Twenty New Zealand white female rabbits weighing approximately 2.5-3 kg were used in the study. The contractile response of clitoral cavernous smooth muscle strips in response to phenylephrine (PE; 10(-9)-10(-4) M) were observed in rabbits. Additionally, DHEA/DHEAS effects on phenylephrine-induced contraction and/or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. DHEA/DHEAS did not elicit any remarkable response in the resting state. However, both DHEA and DHEAS evoked dose-dependent relaxations of PE-induced contraction. The contractile responses to high potassium were significantly decreased in the DHEA/DHEAS-pretreated strips, compared with the DHEA/DHEAS-nontreated strips. Additionally, contractions by Bay K 8644 (10(-7)-10(-6) M) treatment were also significantly inhibited by DHEA/DHEAS. DHEA-induced relaxation responses were stronger than DHEAS-induced relaxation responses. Various K channel blockers, tetraethylammonium (TEA; 1 mM, 10 mM), 4-aminopyridine (10 microM) and glibenclamide (10 microM) did not affect the DHEA/DHEAS-induced relaxation on muscle strips contracted by PE. Relaxation responses by acetylcholine or sodium nitroprusside (SNP) were not changed after DHEA/DHEAS pretreatment. DHEA/DHEAS was found to induce a relaxation response in rabbit clitoral cavernosal smooth muscle, and this is thought to be mediated by direct inhibition of a voltage-dependent calcium

  18. Development of transplant vasculopathy in aortic allografts correlates with neointimal smooth muscle cell proliferative capacity and fibrocyte frequency

    NARCIS (Netherlands)

    Onuta, Geanina; van Ark, Joris; Rienstra, Heleen; Boer, Mark Walther; Klatter, Flip A.; Bruggeman, Cathrien A.; Zeebregts, Clark J.; Rozing, Jan; Hillebrands, Jan-Luuk

    2010-01-01

    Objective: Transplant vasculopathy consists of neointima formation in graft vasculature resulting from vascular smooth muscle cell recruitment and proliferation. Variation in the severity of vasculopathy has been demonstrated. Genetic predisposition is suggested as a putative cause of this variation

  19. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits.

    Directory of Open Access Journals (Sweden)

    Chao Fang

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

  20. Pituitary adenylate cyclase activating polypeptide induces vascular relaxation and inhibits non-vascular smooth muscle activity in the rabbit female genital tract

    DEFF Research Database (Denmark)

    Steenstrup, B R; Ottesen, B; Jørgensen, M

    1994-01-01

    a significant dose-related relaxation on the NA-precontracted vessels. However, pre-incubation of the vessels with 10(-7) M PACAP-38, PACAP-27 and vaso active intestinal polypeptide (VIP) did not induce a general rightward shift of the NA concentration-response curves, although a tendency to inhibition......In vitro effects of two bioactive forms of pituitary adenylate cyclase activating polypeptide (PACAP): PACAP-38 and PACAP-27 were studied on rabbit vascular and non-vascular smooth muscle. Segments of the ovarian artery and muscle strips from the fallopian tube were used. Two series of experiments...... in the low-dose interval was observed. The peptides caused a significant, dose-dependent inhibition of both frequency and amplitude on the fallopian tube smooth muscle activity. The effects of the three peptides on longitudinally as well as transversally cut specimens were alike....

  1. Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    MENG Feng; DENG Zhongduan; NI Juan

    2000-01-01

    To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1)mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL- 1β, 20 ng/mlTNF-lα and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expression of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32p-end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cultured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cultured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-Iβ, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2.3-fold and 1.6-fold, respectively).ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9-fold, 1.7-fold and 1.1-fold, respectively ). The results suggest that calf aortic SMCs could express MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP- 1mRNA and protein, and the former is more effective than the latter.

  2. Aldosterone induces aortic smooth muscle cell apoptosis%醛固酮诱导大鼠主动脉平滑肌细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    闫永吉; 李炯明; 刘建和; 陈戬; 姜永明; 张劲松

    2012-01-01

    目的 观察醛固酮在体内能否诱导主动脉平滑肌细胞凋亡.方法 将24只SD大鼠随机分为3组,每组8只:(1)空白溶剂设为对照组;(2)醛固酮组;(3)醛固酮+血管扩张剂组.渗透泵内分别注入醛固酮(1 μg/h)或空白溶剂,然后埋于大鼠背部皮下.肼苯哒嗪[25 mg/(kg·d)]溶于引用水,每日灌胃1次.8周后脱氧核苷酸末端转移介导的缺口末端标记法(TUNEL)检测凋亡的主动脉平滑肌细胞.结果 醛固酮组和醛固酮+血管扩张剂组大鼠主动脉TUNEL阳性的平滑肌细胞分别占(18.0±1.5)%和(16.5±2.0)%,与对照组(4.7±1.0)%比较,差异有统计学意义(P<0,05);后两组之间差异无统计学意义(P>0.05).结论 醛固酮在体内可以直接诱导主动脉平滑肌细胞凋亡.%Objective To determine whether aldosterone induces aortic smooth muscle cell apoptosis in vivo.Methods 24 Sprague-Dawley rats were randomly divided into 3 groups:vehicle as control; aldosterone and aldosterone plus hydralazine.All animals were then implanted with an osmotic mini-pump containing either aldosterone ( 1 μg/h) or vehicle.Hydralazine [ 25 mg/(kg·d) ] was resolved in drinking water and gavaged once daily.After 8 weeks,aortic smooth muscle cell (ASMC) apoptosis was examined by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay.Results TUNEL-positive aortic smooth muscle cells in aldosterone-infused and aldosterone plus hydralazine rats were ( 18.0± 1.5 ) % and ( 16.5 ± 2.0) % respectively; compared with control rats (4.7 ± 1.0 ) %,there was signifi-cant difference (P < 0.05 ). In contrast,no significant difference was achieved between the latter twogroups (P > 0.05).Conclusion This study' s findings suggest that aldosterone induces aortic smooth muscle cell apoptosis by its direct effect on the aorta.

  3. Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Coronary Artery Disease, Stroke, and Moyamoya Disease, Along with Thoracic Aortic Disease

    Science.gov (United States)

    Guo, Dong-Chuan; Papke, Christina L.; Tran-Fadulu, Van; Regalado, Ellen S.; Avidan, Nili; Johnson, Ralph Jay; Kim, Dong H.; Pannu, Hariyadarshi; Willing, Marcia C.; Sparks, Elizabeth; Pyeritz, Reed E.; Singh, Michael N.; Dalman, Ronald L.; Grotta, James C.; Marian, Ali J.; Boerwinkle, Eric A.; Frazier, Lorraine Q.; LeMaire, Scott A.; Coselli, Joseph S.; Estrera, Anthony L.; Safi, Hazim J.; Veeraraghavan, Sudha; Muzny, Donna M.; Wheeler, David A.; Willerson, James T.; Yu, Robert K.; Shete, Sanjay S.; Scherer, Steven E.; Raman, C.S.; Buja, L. Maximilian; Milewicz, Dianna M.

    2009-01-01

    The vascular smooth muscle cell (SMC)-specific isoform of α-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD and from premature-onset CAD patients independently identified ACTA2 mutations in these patients and premature onset strokes in family members with ACTA2 mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts from patients harboring ACTA2 suggested that increased proliferation of SMCs contributed to occlusive diseases. These results indicate that heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data demonstrate that diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on familial vascular diseases. PMID:19409525

  4. MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

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    Ci-Qiu Yang

    2014-07-01

    Full Text Available Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1 in the formation and development of human abdominal aortic aneurysm (AAA. Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9 expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs extracellular signal regulated kinase (ERK, c-Jun amino terminal kinase (JNK1/2 and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway and SB203580 (inhibitor of the p38 MAPK pathway, but not SP600125 (inhibitor of the JNK1/2 pathway. Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

  5. Effectiveness of cyclooxygenase-2 inhibition in limiting abdominal aortic aneurysm progression in mice correlates with a differentiated smooth muscle cell phenotype.

    Science.gov (United States)

    Mukherjee, Kamalika; Gitlin, Jonathan M; Loftin, Charles D

    2012-12-01

    Abdominal aortic aneurysms (AAAs) are a chronic condition that often progress over years to produce a weakened aorta with increased susceptibility for rupture, and currently, there are no pharmacological treatments available to slow disease progression. AAA development has been characterized by increased expression of cyclooxygenase-2 (COX-2), and inactivation of COX-2 before disease initiation reduces AAA incidence in a mouse model of the disease. The current study determined the effectiveness of COX-2 inhibition on AAA progression when treatment was begun after initiation of the disease. COX-2 inhibitor treatment with celecoxib was initiated after angiotensin II-induced AAA formation in a strain of nonhyperlipidemic mice that we have previously identified as highly susceptible to AAA development. When analyzed at different time points during progression of the disease, celecoxib treatment significantly reduced the incidence and severity of AAAs. The celecoxib treatment also protected the mice from aortic rupture and death. The aneurysmal lesion displayed an altered smooth muscle cell (SMC) phenotype, whereas celecoxib treatment was associated with increased expression of differentiated SMC markers and reduced dedifferentiation marker expression during AAA progression. Maintenance of a differentiated SMC phenotype is associated with the effectiveness of COX-2 inhibition for limiting AAA progression in nonhyperlipidemic mice.

  6. Mepivacaine-induced contraction involves phosphorylation of extracellular signal-regulated kinase through activation of the lipoxygenase pathway in isolated rat aortic smooth muscle.

    Science.gov (United States)

    Lee, Hyo Min; Ok, Seong-Ho; Sung, Hui-Jin; Eun, So Young; Kim, Hye Jung; Lee, Soo Hee; Kang, Sebin; Shin, Il-Woo; Lee, Heon Keun; Chung, Young-Kyun; Choi, Mun-Jeoung; Bae, Sung Il; Sohn, Ju-Tae

    2013-04-01

    Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. This study investigated the arachidonic acid metabolic pathways involved in mepivacaine-induced contraction, and elucidated the associated cellular mechanism with a particular focus on extracellular signal-regulated kinase (ERK) in endothelium-denuded rat aorta. Isolated rat thoracic aortic rings were suspended for isometric tension recording. Cumulative mepivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, indomethacin, NS-398, SC-560, fluconazole, PD 98059, and verapamil. Mepivacaine-induced ERK phosphorylation, 5-lipoxygenase (5-LOX) expression, and cyclooxygenase (COX)-2 expression in rat aortic smooth muscle cells were detected by Western blot analysis in the presence or absence of inhibitors. Mepivacaine produced tonic contraction in isolated endothelium-denuded rat aorta. Quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, NS-398, PD 98059, and verapamil attenuated mepivacaine-induced contraction in a concentration-dependent manner. However, fluconazole had no effect on mepivacaine-induced contraction. PD 98059, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, and indomethacin attenuated mepivacaine-induced ERK phosphorylation. Mepivacaine upregulated 5-LOX and COX-2 expression. These results suggest that mepivacaine-induced contraction involves ERK activation, which is primarily mediated by the 5-LOX pathway and in part by the COX-2 pathway.

  7. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    Science.gov (United States)

    Seo, K. K.; Lee, M. Y.; Lim, S. W.; Kim, S. C.

    1999-01-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  8. Feline immunodeficiency virus and retrovirus-mediated adventitial ex vivo gene transfer to rabbit carotid artery using autologous vascular smooth muscle cells.

    Science.gov (United States)

    Kankkonen, Hanna M; Turunen, Mikko P; Hiltunen, Mikko O; Lehtolainen, Pauliina; Koponen, Jonna; Leppänen, Pia; Turunen, Anna-Mari; Ylä-Herttuala, Seppo

    2004-03-01

    We have developed an ex vivo gene transfer technique to rabbit arterial wall using autologous smooth muscle cells (SMCs). SMCs were harvested from rabbit ear artery, transduced in vitro with vesicular stomatitis virus G-glycoprotein pseudotyped retrovirus or feline immunodeficiency virus (FIV) and returned to the adventitial surface of the carotid artery using a periadventitial silicone collar or collagen sheet placed around the artery. Beta-galactosidase (lacZ) and human apolipoprotein E3 (apoE3) cDNAs were used as transgenes. After retrovirus-mediated gene transfer of lacZ the selected cells implanted with high efficiency and expressed lacZ marker gene at a very high level 7 and 14 days after the operation. The level of lacZ expression decreased thereafter but was still detectable 12 weeks after the gene transfer, and was exclusively localized to the site of cell implantation inside the collar. Utilizing FIV vector expressing apoE3, low levels of apoE were measured from serum collected from a low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic rabbits 1 month after the gene transfer. The physiological effect of apoE expression was detected as transiently elevated serum cholesterol levels. The results indicate that the model can be used for high efficiency local gene transfer in arteries, e.g. during vascular surgery. The model is also valuable for studying expression, stability and safety of new gene transfer vectors and their expression products in vivo.

  9. Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Yao-Chang Chen

    2015-04-01

    Full Text Available Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its effect on human vascular smooth muscle cells (VSMCs has not been elucidated. We examined the effects and the mechanisms of action of dihydroaustrasulfone alcohol on proliferation, migration and phenotypic modulation of human aortic smooth muscle cells (HASMCs. Dihydroaustrasulfone alcohol significantly inhibited proliferation, DNA synthesis and migration of HASMCs, without inducing cell death. Dihydroaustrasulfone alcohol also inhibited platelet-derived growth factor (PDGF-induced expression of cyclin-dependent kinases (CDK 2, CDK4, cyclin D1 and cyclin E. In addition, dihydroaustrasulfone alcohol inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2, whereas it had no effect on the phosphorylation of phosphatidylinositol 3-kinase (PI3K/(Akt. Moreover, treatment with PD98059, a highly selective ERK inhibitor, blocked PDGF-induced upregulation of cyclin D1 and cyclin E and downregulation of p27kip1. Furthermore, dihydroaustrasulfone alcohol also inhibits VSMC synthetic phenotype formation induced by PDGF. For in vivo studies, dihydroaustrasulfone alcohol decreased smooth muscle cell proliferation in a rat model of restenosis induced by balloon injury. Immunohistochemical staining showed that dihydroaustrasulfone alcohol noticeably decreased the expression of proliferating cell nuclear antigen (PCNA and altered VSMC phenotype from a synthetic to contractile state. Our findings provide important insights into the mechanisms underlying the vasoprotective actions of dihydroaustrasulfone alcohol and suggest that it may be a useful therapeutic agent

  10. Iloprost and vitamin C attenuates acute myocardial injury induced by suprarenal aortic ischemia-reperfusion in rabbits.

    Science.gov (United States)

    Iriz, E; Iriz, A; Take, G; Ozgul, H; Oktar, L; Demirtas, H; Helvacioglu, F; Arslan, M

    2015-01-01

    The aim of this study was to evaluate antioxidant and cytoprotective effects of iloprost and Vitamin C in a distant organ after abdominal aorta ischemia-reperfusion injury. Twenty-eight New Zealand rabbits weighing 2,400-2,800 g were used for this study. The rabbits were divided into four equal groups. These groups are control group, sham group, iloprost group, and iloprost+vitamin C group. Suprarenal aorta was occluded with a vascular clamp. Following 30 minutes of ischemia, the vascular clamp was removed. Rabbits in group 3 received 10 ng/kg/min iloprost and those in group 4 received 10 ng/kg/min iloprost and 10 mg/kg vitamin C. At the end of the reperfusion period, the rabbits were sacrificed by a high intraperitoneal dose of xylazine+ketamine injection. Myocardial tissue samples were taken for electron microscopic analysis. We evaluated SOD, MDA and catalase in myocardial tissue samples. Iloprost and iloprost+vitamin C groups significantly reduced the oxidative stress markers in tissue samples (pvitamin C administration (pvitamin C showed an attenuation of ischemia-reperfusion injury in distant organs (Tab. 3, Fig. 4, Ref. 30).

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

    Science.gov (United States)

    Wang, Chunmao; Qian, Xiangyang; Sun, Xiaogang; Chang, Qian

    2015-12-01

    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.

  12. Up and Down Expression of Androgen Receptor,Estrogen Receptor beta and Platelet Derived Growth Factor beta by Testosterone in Aortic Vascular Smooth Muscle Tissues

    Institute of Scientific and Technical Information of China (English)

    Wu Saizhu; Lv Hongsong; Zhou Kexiang; Sun Fei; Ma Rui; Zheng Hua; Wei Heming; Rong Zhiyi

    2004-01-01

    Objectives To investigate the effects of testosterone enanthate(TE) on serum lipids and lipoproteins metabolism and the expression of androgen receptor ( AR), estrogen receptor beta ( ER -β) and platelet derived growth factor beta (PDGFR-β ) in aortic vascular smooth muscle tissues(VSMTs). Methods Forty aged male rats were randomly divided into 4 groups, group A (placebo group),group B (2.5 mg/kg intramuscular injection of TE once a week ), group C (5.0 mg/kg intramuscular injection of TE once a week ), group D ( 10.0 mg,/kg intramuscular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The expression of AR , ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0.01 ).Compared with the other groups, average serum TC was also lower in group D ( p < 0.05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ± 21.74, 125.38 ± 28.68 and 101.98 ±15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kgand 10.0 mg/kg, respectively , the expression of ER -β could be regulated by TE: 92.34 ± 18.68, 47.72 ±18.12, 82.13 ±23.50, and the expression of PDGFR -β could be regulated as well by TE: 219.70 ± 45.59,50.16 ± 9.72, 125.36 ± 15.74 ( Data for AR , ER - βand PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5.0 mg/kg can stimulate the expression of AR, but inhibite the expression of PDGFR. Testosterone enanthate at the concentrations of 5.0 mg/kg and 10.0 mg/kg can inhibite the expression of ER - β.

  13. Advanced glycation end products promote human aortic smooth muscle cell calcification in vitro via activating NF-κB and down-regulating IGF1R expression

    Institute of Scientific and Technical Information of China (English)

    Yi WANG; Zhen-yu ZHANG; Xiao-qing CHEN; Xiang WANG; Heng CAO; Shao-wen LIU

    2013-01-01

    Aim:To investigate the effects of advanced glycation end products (AGEs) on calcification in human aortic smooth muscle cells (HASMCs) in vitro and the underlying mechanisms.Methods:AGEs were artificially prepared.Calcification of HASMCs was induced by adding inorganic phosphate (Pi,2 mmol/L) in the media,and observed with Alizarin red staining.The calcium content in the supernatant was measured using QuantiChrome Calcium Assay Kit.Expression of the related mRNAs and proteins was analyzed using real-time PCR and Western blot,respectively.Chromatin immunoprecipitation (ChIP) assay was used to detect the binding of NF-κB to the putative IGF1R promoter.Results:AGEs (100 μg/mL) significantly enhanced Pi-induced calcification and the levels of osteocalcin and Cbfα1 in HASMCs.Furthermore,the treatment decreased the expression of insulin-like growth factor 1 receptor (IGF1R).Over-expression of IGF1R in HASMCs suppressed the AGEs-induced increase in calcium deposition.When IGF1R expression was knocked down in HASMCs,AGEs did not enhance the calcium deposition.Meanwhile,AGEs time-dependently decreased the amounts of IκBα and Flag-tagged p65 in the cytoplasmic extracts,and increased the amount of nuclear p65 in HASMCs.In the presence of NF-κB inhibitor PDTC (50 μmol/L),the AGEs-induced increase in calcium deposition was blocked.Over-expression of p65 significantly enhanced Pi-induced mineralization,but suppressed IGF1R mRNA level.Knockdown of p65 suppressed the AGEs-induced increase in calcium deposition,and rescued the IGF1R expression.The ChIP analysis revealed that NF-κB bound the putative IGF1R promoter at position-230 to-219 bp.The inhibition of IGF1R by NF-κB was abolished when IGF1R reporter plasmid contained mutated binding sequence for NF-κB or an NF-κB reporter vector.Conclusion:The results demonstrate that AGEs promote calcification of human aortic smooth muscle cells in vitro via activation of NF-κB and down-regulation of IGF1R expression.

  14. A new image-based process for quantifying hemodynamic contributions to long-term morbidity in a rabbit model of aortic coarctation

    Science.gov (United States)

    Wendell, David C.; Dholakia, Ronak J.; Larsen, Paul M.; Menon, Arjun; LaDisa, John F., Jr.

    2010-03-01

    Coarctation of the aorta (CoA) is associated with reduced life expectancy despite successful surgical treatment. Interestingly, much of the related long-term morbidity can be explained by abnormal hemodynamics, vascular biomechanics and cardiac function. MRI has played an important role in assessing coarctation severity, but the heterogeneity and small number of patients at each center presents an obstacle for determining causality. This work describes optimized imaging parameters to create computational fluid dynamics (CFD) models revealing changes in hemodynamics and vascular biomechanics from a rabbit model. CoA was induced surgically at 10 weeks using silk or dissolvable ligatures to replicate native and end-to-end treatment cases, respectively. Cardiac function was evaluated at 32 weeks using a fastcard SPGR sequence in 6-8 two-chamber short-axis views. Left ventricular (LV) volume, ejection fraction, and mass were quantified and compared to control rabbits. Phase contrast (PC) and angiographic MRI were used to create CFD models. Ascending aortic PCMRI data were mapped to the model inflow and outflow boundary conditions replicated measured pressure (BP) and flow. CFD simulations were performed using a stabilized finite element method to calculate indices including velocity, BP and wall shear stress (WSS). CoA models displayed higher velocity through the coarctation region and decreased velocity elsewhere, leading to decreased WSS above and below the stenosis. Pronounced wall displacement was associated with CoA-induced changes in BP. CoA caused reversible LV hypertrophy. Cardiac function was maintained, but caused a persistent hyperdynamic state. This model may now be used to investigate potential mechanisms of long-term morbidity.

  15. Anti-atherogenic effect of trivalent chromium-loaded CPMV nanoparticles in human aortic smooth muscle cells under hyperglycemic conditions in vitro

    Science.gov (United States)

    Ganguly, Rituparna; Wen, Amy M.; Myer, Ashley B.; Czech, Tori; Sahu, Soumyadip; Steinmetz, Nicole F.; Raman, Priya

    2016-03-01

    Atherosclerosis, a major macrovascular complication associated with diabetes, poses a tremendous burden on national health care expenditure. Despite extensive efforts, cost-effective remedies are unknown. Therapies for atherosclerosis are challenged by a lack of targeted drug delivery approaches. Toward this goal, we turn to a biology-derived drug delivery system utilizing nanoparticles formed by the plant virus, Cowpea mosaic virus (CPMV). The aim herein is to investigate the anti-atherogenic potential of the beneficial mineral nutrient, trivalent chromium, loaded CPMV nanoparticles in human aortic smooth muscle cells (HASMC) under hyperglycemic conditions. A non-covalent loading protocol is established yielding CrCl3-loaded CPMV (CPMV-Cr) carrying 2000 drug molecules per particle. Using immunofluorescence microscopy, we show that CPMV-Cr is readily taken up by HASMC in vitro. In glucose (25 mM)-stimulated cells, 100 nM CPMV-Cr inhibits HASMC proliferation concomitant to attenuated proliferating cell nuclear antigen (PCNA, proliferation marker) expression. This is accompanied by attenuation in high glucose-induced phospho-p38 and pAkt expression. Moreover, CPMV-Cr inhibits the expression of pro-inflammatory cytokines, transforming growth factor-β (TGF-β) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), in glucose-stimulated HASMCs. Finally glucose-stimulated lipid uptake is remarkably abrogated by CPMV-Cr, revealed by Oil Red O staining. Together, these data provide key cellular evidence for an atheroprotective effect of CPMV-Cr in vascular smooth muscle cells (VSMC) under hyperglycemic conditions that may promote novel therapeutic ventures for diabetic atherosclerosis.

  16. Aortic dissection

    Science.gov (United States)

    Aortic aneurysm - dissecting; Chest pain - aortic dissection; Thoracic aortic aneurysm - dissection ... the chest and abdomen (the descending aorta). Aortic dissection most often happens because of a tear or ...

  17. Retrieval of rat aortic smooth muscle cells as intact cell sheet for regenerative medicine: a cost effective approach using photo polymerization.

    Science.gov (United States)

    Mukundan, Lakshmi M; Nirmal, Remya; Thomas, Lynda V; Sajeev, U S; Nair, Prabha D

    2011-10-01

    Cell-based therapeutics are promising routes for the regeneration of damaged cells and organs. The recovery of cells cultured in vitro for such applications requires the use of proteolytic enzymes which deteriorate its property by disruption of cell-cell and cell-matrix interactions. Intact cell sheets can be retrieved with the use of thermo responsive polymer grafted on to the culture plates. Our study presents the use of photo-polymerization as a simple and inexpensive way to create thermo-responsive culture surfaces for the detachment of intact cell sheet. Poly (N-isopropyl acrylamide) (PNIPAAm) was synthesized by photo-polymerization and characterized by NMR spectroscopy, differential scanning calorimetry and gel permeation chromatography. Thermo-responsive culture dishes were prepared by the coating method and characterized for its thermo-responsive efficacy using FTIR spectroscopy and water contact angle measurements. Atomic force microscopy depicted the thin coating achieved with this method is similar to the conventional grafting method. Suitability for cell culture and cell sheet retrieval was assessed by culturing rat aortic smooth muscle cells in the PNIPAAm coated tissue culture plates. The cells remained viable as evident from the live dead assay and the cell sheet was detached by low temperature treatment. The results demonstrate a versatile method for creating thermo responsive culture surfaces while eliminating the use of expensive radiation sources for the conventional grafting method. © Springer Science+Business Media B.V. 2011

  18. Effects of sodium selenite on vascular smooth muscle reactivity.

    Science.gov (United States)

    Togna, G; Russo, P; Pierconti, F; Caprino, L

    2000-02-01

    The effects of sodium selenite (Na(2)SeO(3)) on the vascular smooth muscle reactivity of rabbit aorta were studied. In isolated rabbit aorta, Na(2)SeO(3) inhibited contractile response to phenylephrine and developed a lasting contracture in the vascular tissue. Relaxation in phenylephrine-precontracted aortic rings induced by sodium nitroprusside and 8-bromo-guanosine 3':5'-cyclic-monophosphate was also inhibited. Preliminary data obtained with ascorbic acid suggested a partial involvement of an oxidative mechanism. Excluding the possibility that Se damages actin or modifies its distribution (immunohistochemical evaluation), results indicate that Se alters vascular smooth muscle reactivity by inhibiting both its contracting and relaxing properties. Calcium-dependent mechanisms appear to be primarily involved and an interference with calcium re-uptake by sarcoplasmic reticulum as a possible site of Se vascular action could be hypothesized.

  19. Chronic administration of imipramine but not agomelatine and moclobemide affects the nitrergic relaxation of rabbit corpus cavernosum smooth muscle.

    Science.gov (United States)

    Gocmez, Semil Selcen; Utkan, Tijen; Gacar, Nejat

    2013-08-15

    Sexual dysfunction is a common and underestimated effect of antidepressants. However, the mechanism by which these drugs cause erectile dysfunction is unclear. We investigated the reactivity of the corpus cavernosum of rabbits that were treated with either chronic imipramine, which is a tricyclic agent; agomelatine, which is a melatonergic agonist and serotonin 5HT(2c) antagonist; or moclobemide, which is a reversible inhibitor of monoamine-oxidase A. Twenty rabbits were randomly divided into four groups: the control group (n=5), the imipramine-treated group (n=5), which received i.p. injections of 10 mg/kg/day of imipramine, the moclobemide-treated group (n=5), which received i.p. injections of 20 mg/kg/day of moclobemide, and the agomelatine-treated group (n=5), which was orally administered 10 mg/kg/day of agomelatine. The reactivities of corpus cavernosum tissue obtained from the antidepressant-treated and the control groups were studied in organ chambers after the animals were subjected to 21 days of drug administration. The acetylcholine-induced endothelium-dependent and the electrical field stimulation (EFS)-induced neurogenic relaxation of the corpus cavernosum of the imipramine-treated group was significantly decreased compared with the control group. However, neither the acetylcholine- nor EFS-induced relaxation was changed in the moclobemide- or agomelatine-treated groups. There were no change in the relaxant response to the nitric oxide (NO) donor sodium nitroprusside and contractile response to KCl between the groups. This study suggests that chronic imipramine treatment but not agomelatine and moclobemide treatments causes significant functional changes in the penile erectile tissue of rabbits and that these changes may contribute to the development of impotence.

  20. A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits

    OpenAIRE

    Yin, Weidong; Yuan, Zhonghua; Wang, Zongbao; Yang, Baotang; Yang, Yongzong

    2002-01-01

    A new and convenient animal model for studying peripheral vascular and coronary artery disease in diabetes was established in this study. Male New Zealand White rabbits weighing approximately 2 kg were divided into 2 groups: a normal control group fed standard laboratory chow and a diabetogenic diet–fed group received a high-fat/high-sucrose diet. The high-fat/high-sucrose diet (contained 10% lard and 37% sucrose) feeding was maintained for 6 months. Plasma total cholesterol, high-density lip...

  1. Effect of cholesterol lowering on stiffness of aortic and femoral arterial walls in rabbits on a high fat diet

    Institute of Scientific and Technical Information of China (English)

    XUE Li; XU Wan-hai; XU Jin-zhi; ZHANG Tong; BI Hong-yuan; SHEN Bao-zhong

    2009-01-01

    Background Researches in arterial elasticity have increased over the past few years. We investigated the effects of simvastatin on vascular stiffness in fat fed rabbits by ultrasonography.Methods Thirty rabbits were assigned randomly to 3 groups: normal control group (A), the cholesterol group (B), simvastatin group (C: high fat diet for 4 weeks and high fat diet + simvastatin for further 4 weeks). Stiffness coefficient, pressure strain elastic modulus and velocity of pulse waves in abdominal aorta and femoral artery were measured by ultrasonographic echo tracking at the end of the 4th and the 8th weeks.Results At the end of the 4th week, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly increased in group B compared with those in group A. Similarly, at the end of the 8th week, the same parameters of abdominal aorta were significantly increased in group B compared with those in group A. In contrast, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly decreased in group C compared with those in group B, however, there was no significant difference in parameters of abdominal aorta between groups B and C.Conclusion Short term administration of simvastatin can improve the elasticity of femoral artery but not abdominal aorta.

  2. Effects of integrin α5β1 on the proliferation and migration of human aortic vascular smooth muscle cells.

    Science.gov (United States)

    Song, Yan; Qin, Xiaoyu; Wang, Hanjie; Miao, Renying; Zhang, Yonggan; Miao, Chaofeng; Wang, Zifan

    2016-02-01

    Integrin (ITG) α5β1 is a dominant fibronectin receptor that is abundantly expressed on the surface of vascular smooth muscle cells (VSMCs). However, the association between integrin α5β1 and the proliferation and migration of VSMCs has yet to be elucidated. The aim of the present study was to characterize the roles of ITGα5 and ITGβ1 in the proliferation and migration of VSMCs, and to determine the effects of ITGα5β1 on integrin-linked kinase (ILK) and focal adhesion kinase (FAK) mRNA expression. Lentiviral expression vectors as well as RNA interference vectors of ITGα5 and ITGβ1 were successfully constructed and transfected into VSMCs to obtain ITGα5‑ and ITGβ1‑overexpressing or -silenced cells, respectively. Cell cycle distribution, proliferation and migration were analyzed in the transfected VSMCs in order to clarify the roles of ITGβ1 and ITGα5 in the proliferation and migration of VSMCs. ITGβ1 was markedly associated with the proliferation and migration of VSMCs, and FAK was shown to be involved in the signaling pathways of ITGβ1. ITGα5 did not exert any effects on VSMCs. The results of the present study may provide a possible therapeutic target for the prevention and treatment of early vascular disease associated with VSMCs.

  3. AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis.

    Science.gov (United States)

    Liu, Yong; Wang, Wei-Ming; Zhang, Xue-Lin; He, Hu-Qiang; Sun, Xiao-Lei; Zeng, Hong; Xu, Xiong-Fei; Huang, Liang; Zhu, Zhi; Zhang, Lei; Zhou, Xiang-Yu; He, Yan-Zheng

    2016-01-01

    The present study aims to investigate whether RAGE promotes the calcification of human arterial smooth muscle cells (HASMCs) and determine the relationshipbetween RAGE and the Wnt/β-catenin signaling pathway in this process. In this study,there were four groups, namelythe blank control group, the non-transfection group, the empty vector group, and the RAGE transfection group.Cells were co-cultured with 10 mmol/L β-glycerophosphoric acid, pyruvate and 20 mg/L AGE. The expression of osteogenic proteins in each group before and after the intervention wasdetected using Western blotting. Short interfering RNA (siRNA) targeting β-catenin was used toinhibitthe expression of β-catenin. HASMCs cultured under normal conditions were usedas the blank control. (1) High RAGE expression was successfully induced in HASMCs according to the results of GFP detection, flow cytometry and Western blotting. (2) Compared with the blank control group, non-transfection group and empty vector group, RAGE transfection enhanced the calcification of cells when incubated with calcification medium plus AGE. (3) The expression of RAGE, β-catenin, OPG and Cbfa1 proteins in the blank control group, empty vector group and RAGE transfection group wasnot significantly enhanced after intervention. However, expression of the proteins in the RAGE transfection group was much higher than those of the other groups. (4) Compared with the RAGE transfection group and control siRNA group, the cells transfected with β-catenin siRNA and cultured with interventional drugs showed significant inhibition of the expression of the downstream Cbfa1 and OPG genes. Increased expression of RAGE promoted calcification in HASMCs and up regulated the β-catenin, OPG and Cbfa1 genes. RAGE may activate the downstream genes via the Wntβ-catenin pathway, thereby promoting HASMC differentiation into osteogenic cells and calcification.

  4. Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.

    Science.gov (United States)

    Wang, Xisheng; Mei, Yunqing; Ji, Qiang; Feng, Jing; Cai, Jianzhi; Xie, Shiliang

    2015-07-01

    The excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia. In a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry. Transfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA. We confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  5. Nitric oxide production and inducible nitric oxide synthase protein expression in human abdominal aortic aneurysms and cultured aneurismal smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    LIAO Ming-fang; JING Zai-ping; BAO Jun-min; ZHAO Zhi-qing; MEI Zhi-jun; LU Qing-sheng; CUI Jia-sen; QU Le-feng; ZHANG Su-zhen

    2006-01-01

    Objective:To investigate the production of nitric oxide(NO) and the expression of inducible nitric oxide synthase (iNOS), and their possible role in abdominal aortic aneurysm (AAA). Methods: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by CochranMantel-Haenszel x2 test and Kendall correlation. Results: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P<0.05) and the patients with occlusive arteries (P<0. 05). iNOS protein and media NOx (nitrite+nitrate) also increased in cultured SMCs from human AAA (n=4, P<0.05), while plasma NOx decreased in patients with AAA (n=25) compared to the healthy controls (n= 20). There was a positive correlation between iNOS protein and the degree of inflammation in aneurismal wall (Kendall coefficient = 0. 5032, P = 0. 0029). Conclusion:SMCs and inflammatory cells are main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation, SMCs and oxidative stress.

  6. Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

    Science.gov (United States)

    Morinelli, Thomas A; Walker, Linda P; Velez, Juan Carlos Q; Ullian, Michael E

    2015-02-05

    The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression. We have previously shown this is mediated by β-arrestin-dependent receptor internalization and NF-κB activation. In this study, a specific inhibitor of clathrin-mediated endocytosis (CME), pitstop-2, was used to test the hypothesis that clathrin-dependent internalization of activated AT1A receptor mediates NF-κB activation and subsequent cyclooxygenase 2 expression. Radioligand binding assays, real time qt-PCR and immunoblotting were used to document the effects of pitstop-2 on AngII binding and signaling in RASMC. Laser scanning confocal microscopy (LSCM) was used to image pitstop-2׳s effects on AT1 receptor/GFP internalization in HEK-293 cells and p65 NF-κB nuclear localization in RASMC. Pitstop-2 significantly inhibited internalization of AT1A receptor (44.7% ± 3.1% Control vs. 13.2% ± 8.3% Pitstop-2; n=3) as determined by radioligand binding studies in RASMC. Studies utilizing AT1A receptor/GFP expressed in HEK 293 cells and LSCM confirmed these findings. Pitstop-2 significantly inhibited AngII-induced p65 NF-κB phosphorylation and nuclear localization, COX-2 message and protein expression in RASMC without altering activation of p42/44 ERK or TNFα signaling. Pitstop-2, a specific inhibitor of clathrin-mediated endocytosis, confirms that internalization of activated AT1A receptor mediates AngII activation of cyclooxygenase 2 expression in RASMC. These data provide support for additional intracellular signaling pathways activated through β-arrestin mediated internalization of G protein-coupled receptors, such as AT1A receptors.

  7. Conjugated agent insulin-antisense-c-myb-PS-ODN enhances the inhibitory effect on proliferation of rat aortic artery smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM:Vascular smooth muscle cell (SMC) proliferation and migration from the arterial wall media into the intima are believed to play a critical role in the pathogenesis of restenosis. Several studies have demonstrated that phosphothioate (PS) oligodeoxynucleotides targeted against genes involved in SMC proliferation inhibits in vitro SMC proliferation and migration. However, the therapeutic effect of antisense ODN on the individual who receives the treatment of delivery of the agent depends on the efficacy of this agent in great degree. We investigated the inhibition effect of a novel agent, insulin-antisense-c-myb-PS-ODN on SMC proliferation in vitro. METHODS:The rat aortic artery SMCs were cultured in Dulbecco's modified Eagel's medium. The passage 8 to 13 were used as the experiment. Cell surface receptor binding assay was quantified through counting gamma particles emitted from 125    I labeled insulin. SMC rapid proliferation was brought by stimulation of high concentration of fetal bovine serum (FBS). The novel agent of insulin conjugated to the antisense-c-myb-PS-ODN was obtained via incubation of both in condition of certain reagents, pH, temperature, and ion concentration. The characterization and purification of the agent was performed through HPLC. Inhibition of SMC proliferation was reflected by incorporation rate of trillium labeled thymidine deoxyribonucleotide.RESULTS:The binding efficacy of insulin to the receptor was remarkably increased in SMC cultured in supplement of 20% FBS. The inhibition effect of conjugator insulin-c-myb-antisense-PS-ODN was stronger than that of the simple c-myb-antisense-PS-ODN. The inhibition rate of conjugator and simple form on SMC proliferation were 48.34% and 29.54%, respectively. CONCLUSION:The binding efficacy and specificity of c-myb-antisense-PS-ODN to SMC may be enhanced by the insulin receptor mediation through the insulin-insulin receptor interaction. The insulin-receptor targeted method may be a

  8. Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound

    Directory of Open Access Journals (Sweden)

    João Batista Gadelha de Cerqueira

    2012-10-01

    Full Text Available PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH34(caffeine(NO]C13 (Rut-Caf and sodium nitroprusside (SNP. MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE (1 µM and then concentration-response curves (10-12 - 10-4 M were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM, oxyhemoglobin (10 µM, L-cysteine (100 µM, hydroxicobalamine (100 µM, glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50 and maximum effect (Emax. The substances showed activity through activation of the soluble guanylyl cyclase (sGC, because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09. There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.

  9. Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Son, Youn Kyoung; Hong, Da Hye; Li, Hongliang; Kim, Dae-Joong; Na, Sung Hun; Park, Hongzoo; Jung, Won-Kyo; Choi, Il-Whan; Park, Won Sun

    2014-01-01

    We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca(2+) channel inhibitor, on voltage-dependent K(+) (K(V)) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K(V) currents in a concentration-dependent manner, with an IC(50) of 0.080 μM and a Hill coefficient of 0.76.NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K(V) channel gating. Both the K(V) currents and the inhibitory effect of NNC 55-0396 on K(V) channels were not altered by depletion of extracellular Ca(2+) or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca(2+)-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dosedependently inhibits K(V) currents, independently of Ca(2+)-channel activity and intracellular signaling cascades.

  10. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.

    Science.gov (United States)

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Minami, M; Yoshikawa, J

    1999-03-16

    To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.

  11. EXPRESSION OF TISSUE-TYPE PLASMINOGEN ACTIVATOR IN SMOOTH MUSCLE CELLS OF INJURED ILIAC ARTERIES IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    马晓莉; 黄文英; 佘铭鹏; 李晓惠; 笪冀平

    1996-01-01

    In this experiment, expression of tissue-type plasminogen activator (t-PA) in smooth muscle cells(SMCs) was measured at different iutervals after the arterial injury. In the normal lilac arteries, only low levels of t-PA activity were estimated, t-PA activity in extracts of the iliac arteries increased significantly at the 4th day after the injury, equivalent to the process that SMCs migrated from the media to the intima,and the t-PA activity was then decreased approximately to the normal level at the 7th day. Coexistent to the above data, results from in situ hybridization showed that the expression of t-PA mRNA in the intimaas well as media increased also significantly nr the 4th day after the arterial injury, and at the 7th day, t-PA mRNA was detected only in those SMCs locating closely adjacent to the internal elastic lamina. These results suggest that t-PA might play an important role in SMC migration following endothelial injury, and antagcaaism of t-PA expression and/or activity within the vessel wall might be helpful in intervening the devnlopment of restenosis following angioplasty.

  12. Interaction between hydrogen sulfide/cystathionine γ-lyase and carbon monoxide/heme oxygenase pathways in aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Hong-fang JIN; Jun-bao DU; Xiao-hui LI; Yan-fei WANG; Yin-fang LIANG; Chao-shu TANG

    2006-01-01

    Aim: To investigate the interaction between hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) and carbon monoxide (CO)/heme oxygenase (HO) pathways in aortic smooth muscle cells (ASMC). Methods: The ASMCs were divided into the following groups: (1) the control group; (2) the zinc protoporphyrin (ZnPP) 20 (μmol/L group; (3) the propargylglycine (PPG) 2 mmol/L, 4 mmol/L and 10 mmol/L groups; and (4) the sodium hydrosulfide (NaHS) 1×10-5 mol/L, 1×10-4 mol/L and 1×10-3 mol/L groups. Each of the groups was further divided into 6 h, 12 h, 18 h and 24 h subgroups. The CO level, represented by carboxyhemoglobin (HbCO) content was measured using a spectrophotometric method and H2S content was detected by a sensitive electrode method. CSE and HO-1 expressions were detected by Western blotting. Results: The H2S content in the medium and CSE expression by ASMC were markedly increased by ZnPP compared with the control group. HbCO content in the medium and HO-1 expression by the ASMC started strengthening following 24 h treatment with PPG at 2 mmol/L, but were further strengthened following 18 h and 24 h treatment with PPG at 4 mmol/L compared with the controls (P<0.01). PPG at 10 mmol/L increased the HbCO level in the medium following 18 h treatment and increased HO-1 expression by the ASMC following 12 h treatment. Moreover, NaHS at 1×10-5 mol/L and 1×10-4 mol/L decreased the HbCO level in the medium and HO-1 expression by the ASMC after 6 h and 12 h treatment, while NaHS at 1×10-3 mol/L decreased them at all time points of the treatments. Conclusion: The results suggested that endogenous CO/HO and H2S/CSE pathways inhibited each other in ASMC under physiological conditions.

  13. Immuohistochemical study on smooth muscle cell proliferation, phenotypic modulation, and extracellular matrix accumulation in venous arterial grafts in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-da; ZHU Hai-long

    2002-01-01

    Objective: To study the kinetics and distribution of smooth muscle cell (SMC) proliferation, phenotypic modulation, and various extracellular matrix (ECM) components accumulation during vein graft remodeling. Methods: Normal vein and vein graft in carotid arteries were examined on d 4, d 7, d 14, d 60 and d180 after bypass grafting with immunohistochemical markers of cellular proliferation (proliferating cell nuclear antigen, PCNA), cytoskeletal protein production (α-actin SMC), myosin heavy chain (MHC) isoforms, ECM proteins, and histochemistry (hematoxylin eosin and Elastica-van Gieson stain). Results: Normal veins demonstrated an extremely low level of cellular proliferation and expressed as adult phenotype SMCs in media. After bypass grafting, medial SMCs in the graft appeared to be damaged and began to proliferate on d 4, and subsequently migrated and formed the neointima on d 7. Thereafter, the neointima thickened throughout the 180-day period of the experiment, although the neointimal SMC proliferation decreased after d 14. Meanwhile SMCs underwent a distinct phenotypic change from normal adult type to embryonic type.On d 60, embryonic phenotype SMCs began to return to the adult phenotype, but remain to be present in the neointima for as long as 180 d. ECM components including type Ⅰ collagen, heparin sulfate proteoglucan (HSPG), and dermatan sulfate proteoglcan (decorin) were detected within the neointima on d 7. Thereafter,the accumulation of ECM increased progressively with time. On d 180, a large amount of ECM components were found in the neointima. HSPG mainly accumulated in the superficial and cellular region of the neointima, decorin, on other hand, located in hypocellular area deep in neointima. Type Ⅰ collagen scatted in both regions. The elastic fibers became rich and arranged continuously in the neointima. Conclusion.. The neointima of vein graft was initially formed by proliferation of the embryonic-type SMCs and then thickened infinitely

  14. Aortic insufficiency

    Science.gov (United States)

    ... page, please enable JavaScript. Aortic insufficiency is a heart valve disease in which the aortic valve does not close ... aortic insufficiency Images Aortic insufficiency References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  15. The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K{sup +} channels in rabbit coronary arterial smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongliang; Hong, Da Hye; Kim, Han Sol; Kim, Hye Won [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of); Jung, Won-Kyo [Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737 (Korea, Republic of); Na, Sung Hun [Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, 200-701 (Korea, Republic of); Jung, In Duk; Park, Yeong-Min [Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Choi, Il-Whan, E-mail: cihima@inje.ac.kr [Department of Microbiology, Inje University College of Medicine, Busan, 614-735 (Korea, Republic of); Park, Won Sun, E-mail: parkws@kangwon.ac.kr [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of)

    2015-06-15

    We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K{sup +} (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC{sub 50}) value of 0.81 μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77 ± 0.04 μM{sup −1} s{sup −1} and 2.55 ± 1.50 s{sup −1}, respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2 Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition. - Highlights: • We investigated the effects of CGS 9394B on Kv channels. • CGS 9394B inhibited Kv current in a state-, time-, and use-dependent manner. • Caution is required when using CGS 9394B in vascular function studies.

  16. Effects of Icariin on Physiological Properties of Isolated Small Intestinal Smooth Muscle from the Rabbit%淫羊藿对家兔离体小肠平滑肌生理特性的影响

    Institute of Scientific and Technical Information of China (English)

    付立波; 杨燕平; 付艳平

    2011-01-01

    [Objective] To investigate the effects of Epimedium Icariine on activity of isolated small intestinal smooth muscle from rabbits. [Method] The routine experimental method of small intestinal (duodenum) smooth muscle isolated from rabbits is used to put in homotheimal smooth muscle and connect with tension pickup, signal are input into BL-420E biological function experiment system, then add with different con centrations of Epimedium Icariine solution, the automatic contracting characteristic and changing law in taking Epimedium Icariine before and af ter are recorded. [ Result ] Epimedium Icariine of different density (10 '4, 10 -3,10 -2 mol/L) have a restraining effect on automatic contracting activity of isolated small intestinal smooth muscle whose scope have remarkable differences comparing to taking ethanol before and after. [ Con clusion ] Epimedium Icariine has a direct inhibitory trend on small intestine smooth muscle.%[目的]观察淫羊藿苷对家免离体小肠平滑肌收缩活动的影响.[方法]取家兔离体小肠(十二指肠)肠段,将其置于恒温平滑肌槽中,连接张力传感器,信号输入BL-420E生物机能实验系统,加入不同浓度的淫羊藿苷溶液,分别记录小肠平滑肌的收缩活动.结果不同浓度淫羊藿苷( 10-4、10-3、10-2 mol/L)对小肠平滑肌自发收缩活动有抑制作用,其收缩幅度变化值与用药前比较差异显著.[结论]淫羊藿苷对小肠平滑肌活动有抑制性影响.

  17. Safflower seed polyphenols (N-(p-coumaroyl)serotonin and N-feruloylserotonin) ameliorate atherosclerosis and distensibility of the aortic wall in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits

    National Research Council Canada - National Science Library

    Katsuda, Shin-ichiro; Suzuki, Katsuya; Koyama, Naoto; Takahashi, Michio; Miyake, Masao; Hazama, Akihiro; Takazawa, Kenji

    2009-01-01

    ...)serotonin, N-feruloylserotonin; CS+FS), which are the active components in SSE, on hypercholesterolemia and atherosclerosis, using PWV in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. SSE and CS...

  18. Hazelnut Oil Administration Reduces Aortic Cholesterol Accumulation and Lipid Peroxides in the Plasma, Liver, and Aorta of Rabbits Fed a High-cholesterol Diet

    National Research Council Canada - National Science Library

    HATIPOGLU, Aydan; KANBAGLI, Öznur; BALKAN, Jale; KÜÇÜK, Mutlu; ÇEVIKBAS, Ugur; AYKAÇ-TOKER, Gülçin; BERKKAN, Hakan; UYSAL, Müjdat

    2004-01-01

    Hazelnut oil (HO) is rich in monounsaturated fatty acids and antioxidants. We wanted to investigate the effect of HO on lipid levels and prooxidant-antioxidant status in rabbits fed a high-cholesterol (HC) diet...

  19. Application of Fourier transform infrared spectroscopic imaging to the study of effects of age and dietary l-arginine on aortic lesion composition in cholesterol-fed rabbits

    Science.gov (United States)

    Palombo, Francesca; Cremers, Stephanie G.; Weinberg, Peter D.; Kazarian, Sergei G.

    2009-01-01

    Diet-induced atherosclerotic lesions in the descending thoracic segment of rabbit aorta were analysed ex vivo by micro-attenuated total reflection (ATR)–Fourier transform infrared (FTIR) spectroscopic imaging. The distribution and chemical character of lipid deposits within the arterial wall near intercostal branch ostia were assessed in histological sections from immature and mature rabbits fed cholesterol with or without l-arginine supplements. Previous studies have shown that both these properties change with age in cholesterol-fed rabbits, putatively owing to changes in the synthesis of nitric oxide (NO) from l-arginine. Immature animals developed lesions at the downstream margin of the branch ostium, whereas lipid deposition was observed at the lateral margins in mature animals. Dietary l-arginine supplements had beneficial effects in mature rabbit aorta, with overall disappearance of the plaques; on the other hand, they caused only a slight decrease of the lipid load in lesions at the downstream margin of the ostium in immature rabbits. ATR–FTIR imaging enabled differences in the lipid to protein density ratio of atherosclerotic lesions caused by age and diet to be visualized. Lipid deposits in immature rabbits showed higher relative absorbance values of their characteristic spectral bands compared with those in immature l-arginine-fed rabbits and mature rabbits. The multivariate methods of principal component analysis (PCA) and factor analysis (FA) were employed, and relevant chemical and structural information were obtained. Two distinct protein constituents of the intima–media layer at different locations of the wall were identified using the method of FA. This approach provides a valuable means of investigating the structure and chemistry of complex heterogeneous systems. It has potential for in vivo diagnosis of pathology. PMID:18986964

  20. Effects of Oridonin on Activities of Rabbit' s Intestinal Smooth Muscle%冬凌草甲素对家兔肠平滑肌活动的影响

    Institute of Scientific and Technical Information of China (English)

    杨敏; 卢静; 牟金金; 徐珽

    2012-01-01

    目的 探讨冬凌草甲素对家兔离体肠道平滑肌的影响.方法 以家兔肠张力为指标,给予同一离体盲肠相同剂量的冬凌草甲素粗提物水溶液、乙酰胆碱、硫酸阿托品、新斯的明,对比不同影响;给予不同剂量的冬凌草甲素粗提物水溶液,对比不同影响.结果 冬凌草甲素对家兔肠平滑肌张力无明显影响.结论 家兔肠平滑肌对冬凌草甲素不敏感,这为冬凌草甲素的临床应用提供了可靠的生理依据.%Objective To study the effects of oridonin on the activities of rabbit' s intestinal smooth muscle. Methods With the tensility of intestinal smooth muscle as the index,the changes of contractibility of the intestinal smooth muscle were observed. The effects after administration of the same dosage of the crude extract aqueous solution of oridonin, acetylcholine, atropine sulfate and neostigmine were compared and the effects after administration of different dosages of oridonin were also compared subsequently. Results Obvious effects of oridonin on the contractibility of the intestinal smooth muscle were not observed. Conclusion Intestinal smooth muscle is not sensitive to oridonin,which may provide the reliable basis for the clinical application of oridonin.

  1. Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.

    OpenAIRE

    Williams, B.; Tsai, P.; Schrier, R W

    1992-01-01

    Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface recepto...

  2. Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease.

    Science.gov (United States)

    Netherton, Stuart J; Jimmo, Sandra L; Palmer, Daniel; Tilley, Douglas G; Dunkerley, Heather A; Raymond, Daniel R; Russell, James C; Absher, P Marlene; Sage, E Helene; Vernon, Robert B; Maurice, Donald H

    2002-04-01

    Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aortic VSMCs, levels of expression of cytosolic PDE3 (PDE3A) and PDE3B in +/? and cp/cp VSMCs, as well as activation of these enzymes following activation of the cAMP-protein kinase A signaling cascade, were not different. Our data are consistent with an increased role for PDE3 in regulating cAMP-dependent signaling in cp/cp VSMCs and identify PDE3 as a cellular activity potentially responsible for the phenotype of cp/cp VSMCs.

  3. 不同浓度依托咪酯对内毒素孵育前后兔离体肺、体动脉环张力的影响%Effect of different concentrations of etomidate on the tone of isolated rabbit pulmonary and aortic artery rings before and after LPS incubation

    Institute of Scientific and Technical Information of China (English)

    李玢琳; 张锦; 李娜; 佟冬怡

    2012-01-01

    Objective To observe the effects of etomidate on isolated rabbit pulmonary and aortic artery rings before and after LPS incubation, and provide evidence for narcotic choice of clinic septic shock. Methods The rings of pulmonary and aortic arteries were prepared and randomly divided into 4 groups: normal pulmonary artery rings group, LPS incubated pulmonary artery rings group, normal aortic artery rings group and LPS incubated aortic artery rings group. The effects of etomidate of 1. 0 μmol/L,2. 0 μmol/L, 10. 0 μmol/L on pulmonary and aortic arteries in two groups were observed when phenylephrine( PE )pre-contracting. Results The tone of pulmonary and aortic arteries be fore and after LPS incubated had no significant difference( P > 0. 05 )when 1. 0 μmol/L of etomidate was given; the tone of normal pulmonary and aortic arteries and LPS aortic arteries increased significantly( P 0.05);2.0 μmol/L时,正常肺、主动脉环和LPS孵育后主动脉环张力明显上升(P<0.05);10.0 μmol/L时,LPS孵育的肺、主动脉环的张力较正常肺、主动脉环明显下降(P<0.05).结论 低浓度Eto收缩机制占主导,但随着浓度增加,Eto引起内毒素孵育后肺动脉舒张的程度比体动脉更明显,可能与高浓度Eto抑制血管收缩功能有关.

  4. 9p21.3 Coronary Artery Disease Risk Variants Disrupt TEAD Transcription Factor-Dependent Transforming Growth Factor β Regulation of p16 Expression in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Almontashiri, Naif A M; Antoine, Darlène; Zhou, Xun; Vilmundarson, Ragnar O; Zhang, Sean X; Hao, Kennedy N; Chen, Hsiao-Huei; Stewart, Alexandre F R

    2015-11-24

    The mechanism whereby the 9p21.3 locus confers risk for coronary artery disease remains incompletely understood. Risk alleles are associated with reduced expression of the cell cycle suppressor genes CDKN2A (p16 and p14) and CDKN2B (p15) and increased vascular smooth muscle cell proliferation. We asked whether risk alleles disrupt transcription factor binding to account for this effect. A bioinformatic screen was used to predict which of 59 single nucleotide polymorphisms at the 9p21.3 locus disrupt (or create) transcription factor binding sites. Electrophoretic mobility shift and luciferase reporter assays examined the binding and functionality of the predicted regulatory sequences. Primary human aortic smooth muscle cells (HAoSMCs) were genotyped for 9p21.3, and HAoSMCs homozygous for the risk allele showed reduced p15 and p16 levels and increased proliferation. rs10811656 and rs4977757 disrupted functional TEF-1 TEC1 AbaA domain (TEAD) transcription factor binding sites. TEAD3 and TEAD4 overexpression induced p16 in HAoSMCs homozygous for the nonrisk allele, but not for the risk allele. Transforming growth factor β, known to activate p16 and also to interact with TEAD factors, failed to induce p16 or to inhibit proliferation of HAoSMCs homozygous for the risk allele. Knockdown of TEAD3 blocked transforming growth factor β-induced p16 mRNA and protein expression, and dual knockdown of TEAD3 and TEAD4 markedly reduced p16 expression in heterozygous HAoSMCs. Here, we identify a novel mechanism whereby sequences at the 9p21.3 risk locus disrupt TEAD factor binding and TEAD3-dependent transforming growth factor β induction of p16 in HAoSMCs. This mechanism accounts, in part, for the 9p21.3 coronary artery disease risk. © 2015 American Heart Association, Inc.

  5. Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is associated with increased nuclear factor-kappaB and activator protein-1 activity.

    Science.gov (United States)

    Knipp, Brian S; Ailawadi, Gorav; Ford, John W; Peterson, David A; Eagleton, Matthew J; Roelofs, Karen J; Hannawa, Kevin K; Deogracias, Michael P; Ji, Baoan; Logsdon, Craig; Graziano, Kathleen D; Simeone, Diane M; Thompson, Robert W; Henke, Peter K; Stanley, James C; Upchurch, Gilbert R

    2004-01-01

    To determine the mechanism underlying increased expression and activity of matrix metalloproteinase 9 (MMP-9) by rat aortic smooth muscle cells (RA-SMC) after inhibition of inducible nitric oxide synthase (iNOS). Treatment of interleukin-1beta-stimulated RA-SMC with aminoguanidine led to an increase of 96% in MMP-9 activity (P = 0.003) by gelatin zymography, a 40% increase in pro-MMP-9 protein (P = 0.018) by Western blot, and a 155% increase in MMP-9 mRNA (P = 0.06) by reverse transcription polymerase chain reaction. Aminoguanidine also caused a 26% decrease in cytosolic IkappaB levels (P = 0.014) by Western blot, as well as a 97% increase in nuclear factor-kappaB binding and a 216% increase in activator protein-1 binding as measured by electrophoretic mobility shift assay. No significant changes were noted in MMP-2 or TIMP-1 expression, protein levels, or activity after aminoguanidine administration. MMP-9 expression and activity is increased in cytokine stimulated RA-SMCs after iNOS inhibition, coincident with activation of the nuclear factor-kappaB and activator protein-1 pathways. We speculate that local derangements in iNOS may favor MMP-9-dependent vessel wall damage in vivo via an inflammatory cascade mechanism.

  6. Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest.

    Science.gov (United States)

    Yoo, Su-Hyang; Lim, Yong; Kim, Seung-Jung; Yoo, Kyu-Dong; Yoo, Hwan-Soo; Hong, Jin-Tae; Lee, Mi-Yea; Yun, Yeo-Pyo

    2013-01-01

    Vascular diseases such as atherosclerosis and restenosis artery angioplasty are associated with vascular smooth muscle cell (VSMC) proliferation and intimal thickening arterial walls. In the present study, we investigated the inhibitory effects of sulforaphane, an isothiocyanate produced in cruciferous vegetables, on VSMC proliferation and neointimal formation in a rat carotid artery injury model. Sulforaphane at the concentrations of 0.5, 1.0, and 2.0 μM significantly inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation in a concentration-dependent manner, determined by cell count. The IC50 value of sulforaphane-inhibited VSMC proliferation was 0.8 μM. Sulforaphane increased the cyclin-dependent kinase inhibitor p21 and p53 levels, while it decreased CDK2 and cyclin E expression. The effects of sulforaphane on vascular thickening were determined 14 days after the injury to the rat carotid artery. The angiographic mean luminary diameters of the group treated with 2 and 4 μM sulforaphane were 0.25±0.1 and 0.09±0.1 mm², respectively, while the value of the control groups was 0.40±0.1 mm², indicating that sulforaphane may inhibit neointimal formation. The expression of PCNA, maker for cell cycle arrest, was decreased, while that of p53 and p21 was increased, which showed the same pattern as one in in-vitro study. These results suggest that sulforaphane-inhibited VSMC proliferation may occur through the G1/S cell cycle arrest by up-regulation of p53 signaling pathway, and then lead to the decreased neointimal hyperplasia thickening. Thus, sulforaphane may be a promising candidate for the therapy of atherosclerosis and post-angiography restenosis. © 2013.

  7. Apoptosis of vascular smooth muscle cells induced by cholesterol and its oxides in vitro and in vivo.

    Science.gov (United States)

    Yin, J; Chaufour, X; McLachlan, C; McGuire, M; White, G; King, N; Hambly, B

    2000-02-01

    The ability of cholesterol and its oxides to induce apoptosis in vascular smooth muscle cells in tissue culture and in a rabbit model of atherosclerosis was evaluated. Apoptosis was detected using DNA laddering and in situ end-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, were found to inhibit proliferation and induce apoptosis of vascular smooth muscle cells in tissue culture. 7-ketocholesterol was found to be the most potent inhibitor of proliferation, while 25-hydroxycholesterol was found to be the most potent inducer of apoptosis. These data suggest that the inhibition of proliferation and the induction of apoptosis by cholesterol oxides within vascular smooth muscle cells use different pathways, suggesting a differential role for these cholesterol oxides within the arterial wall. Cholesterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we found that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor determining apoptosis in our model was the balloon injury.

  8. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  9. NF-κB-Dependent Upregulation of NCX1 Induced by Angiotensin II Contributes to Calcium Influx in Rat Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Liu, Bei; Yang, Lixia; Zhang, Bin; Kuang, Chenwei; Huang, Shiliang; Guo, Ruiwei

    2016-11-01

    The reverse mode of Na(+)/Ca(2+) exchanger (NCX) 1 can transport Ca(2+) into cells and is involved in the contractile regulation of vascular smooth muscle cells (VSMCs) and the development of hypertension. We hypothesized that upregulation of NCX1 expression induced by angiotensin II (Ang II) could be dependent on activation of nuclear factor-kappa B (NF-κB) and contributes to Ca(2+) influx in VSMCs. An osmotic minipump was implanted for administration of Ang II in Sprague-Dawley rats, and blood pressure, as well as NCX1 expression, in the aorta was measured. VSMCs were cultured to verify that Ang II-upregulated NCX1 expression is dependent on activation of NF-κB and contributes to Ca(2+) influx. Ang II-upregulated NCX1 expression in rat aortas (2.1-fold at day 6) and VSMCs (1.7-fold at 24 hours) and NF-κB knockdown and p38 mitogen-activated protein kinase (MAPK) inhibitor resulted in 2.1- and 2.0-fold decreases in Ang II-upregulated NCX1 expression in VSMCs. KB-R7943 (an inhibitor of NCX1 reversal) and NCX1 knockdown decreased Ang II-induced Ca(2+) influx 1.4- and 1.3- fold, respectively. KB-R7943 and removal of extracellular Na(+) decreased Ang II-initiated store depletion-mediated Ca(2+) entry by 1.5- and 1.3-fold, respectively. Moreover, NF-κB knockdown and use of a p38 MAPK inhibitor resulted in about 1.3-fold decreases in Ang II-induced Ca(2+) influx through activation of reverse-mode NCX1. Ang II upregulates NCX1 expression through p38 MAPK and NF-κB pathways, and reverse-mode NCX1 plays an important part in Ang II-induced Ca(2+) influx in VSMCs, which may be associated with Ang II-initiated store-operated channel entry. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  10. Comparison of the effects of fish oil and olive oil on blood lipids and aortic atherosclerosis in Watanabe heritable hyperlipidaemic rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Hansen, Birgit Fischer; Hansen, Jørgen Fischer

    1998-01-01

    To compare the effects of fish oil and olive oil on the development of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits, 6-week-old animals were given a daily dose (1.5 ml/kg body weight) of fish oil (n 10) or olive oil (n 10) by oral administration for 16 weeks. Plasma...... of treatment, and throughout the study thereafter, blood lipids were significantly (P oil group than in the olive-oil group (cholesterol: 17.0 v. 30.3 mmol/l, triacylglycerols 2.97 v. 6.25 mmol/l, at termination). In the fish-oil group cholesterol was significantly lower...... in intermediate-density lipoproteins (2.69 v. 6.76 mmol/l) and VLDL (3.36 v. 11.51 mmol/l). Triacylglycerol levels of intermediate-density lipoproteins and VLDL in the fish-oil group were also significantly lower when compared with the olive-oil group (0.54 v 1.36 mmol/l and 0.92 v. 2.87 mmol/l respectively...

  11. Influences of quercetin on contraction of small intestinal smooth muscle of rabbits in vitro and its mechanism of action%槲皮素对兔离体肠平滑肌张力的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    唐学敏; 李家栋; 杨静; 王巧云

    2013-01-01

    目的:观察槲皮素对兔离体回肠平滑肌肌张力的影响,并探讨其作用机制.方法:试验采用经典的离体小肠灌流技术,观察槲皮素(quercetin,Que)对回肠平滑肌自主收缩活动以及乙酰胆碱(acetylcholine,Ach)、氯化钡及组胺(histamine)所致痉挛性收缩肠平滑肌张力的影响.结果:槲皮素(20,60,1 00 mol·L-1)能剂量依赖性的抑制家兔离体小肠平滑肌自发性收缩,对乙酰胆碱,组胺和氯化钡所致的兔离体肠痉挛性收缩也具有剂量依赖性抑制作用.在无钙台式液中,槲皮素可明显抑制Ach引起的回肠平滑肌收缩(P<0.01),亦能使氯化钙量效曲线下移.槲皮素对Bay K8644(0.5 mol·L-1)引起的回肠平滑肌收缩亦有明显抑制作用(P<0.01).结论:槲皮素明显抑制了家兔离体小肠平滑肌的收缩活动,其机制与抑制外钙内流及内钙释放有关.%OBJECTIVE To observe the influences of quercetin on the contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism of action. METHODS With the isothermal perfusion of small intestine in vitro , the relaxant effects and related mechanism of quercetin were studied on the spontaneous contraction of small intestinal and contraction induced by Ach, histamine and Bacl2. RESULTS Quercetin reduced the actonmic contractivity of small intestine smooth muscle antonomic and the cmtractinity induced by acetylcholine.BaCl2 and histamine (P<0. 01). Quercetin were found to inhibit the contraction induced bv acetychline in the Ca2+ -free Tyrode's solution and the CaCl2 cumulative dose-response curves with a lower maximal response. And it could also depress the contraction agonized by Bay K8644 in small intestinal smooth muscle. CONCLUSION Quercetin inhibits the contraction of small intestinal smooth muscle of rabbits in vitro. The mechanism may be related to inhibit the extracellular Ca2+ inflowing via cell membrane channel and intracellular Ca2+ releasing via

  12. Experimental Animal Models Evaluating the Causal Role of Lipoprotein(a) in Atherosclerosis and Aortic Stenosis.

    Science.gov (United States)

    Yeang, Calvin; Cotter, Bruno; Tsimikas, Sotirios

    2016-02-01

    Lipoprotein(a) [Lp(a)], comprised of apolipoprotein(a) [apo(a)] and a low-density lipoprotein-like particle, is a genetically determined, causal risk factor for cardiovascular disease and calcific aortic valve stenosis. Lp(a) is the major plasma lipoprotein carrier of oxidized phospholipids, is pro-inflammatory, inhibits plasminogen activation, and promotes smooth muscle cell proliferation, as defined mostly through in vitro studies. Although Lp(a) is not expressed in commonly studied laboratory animals, mouse and rabbit models transgenic for Lp(a) and apo(a) have been developed to address their pathogenicity in vivo. These models have provided significant insights into the pathophysiology of Lp(a), particularly in understanding the mechanisms of Lp(a) in mediating atherosclerosis. Studies in Lp(a)-transgenic mouse models have demonstrated that apo(a) is retained in atheromas and suggest that it promotes fatty streak formation. Furthermore, rabbit models have shown that Lp(a) promotes atherosclerosis and vascular calcification. However, many of these models have limitations. Mouse models need to be transgenic for both apo(a) and human apolipoprotein B-100 since apo(a) does not covalently associated with mouse apoB to form Lp(a). In established mouse and rabbit models of atherosclerosis, Lp(a) levels are low, generally model whereas over 40 isoforms exist in humans. Mouse models should also ideally be studied in an LDL receptor negative background for atherosclerosis studies, as mice don't develop sufficiently elevated plasma cholesterol to study atherosclerosis in detail. With recent data that cardiovascular disease and calcific aortic valve stenosis is causally mediated by the LPA gene, development of optimized Lp(a)-transgenic animal models will provide an opportunity to further understand the mechanistic role of Lp(a) in atherosclerosis and aortic stenosis and provide a platform to test novel therapies for cardiovascular disease.

  13. Action of niflumic acid on evoked and spontaneous calcium-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein.

    Science.gov (United States)

    Hogg, R. C.; Wang, Q.; Large, W. A.

    1994-01-01

    1. The action of niflumic acid was studied on spontaneous and evoked calcium-activated chloride (ICl(Ca)) and potassium (IK(Ca)) currents in rabbit isolated portal vein cells. 2. With the nystatin perforated patch technique in potassium-containing solutions at a holding potential of -77 mV (the potassium equilibrium potential), niflumic acid produced a concentration-dependent inhibition of spontaneous transient inward current (STIC, calcium-activated chloride current) amplitude. The concentration to reduce the STIC amplitude by 50% (IC50) was 3.6 x 10(-6) M. 3. At -77 mV holding potential, niflumic acid converted the STIC decay from a single exponential to 2 exponential components. In niflumic acid the fast component of decay was faster, and the slow component was slower than the control decay time constant. Increasing the concentration of niflumic acid enhanced the decay rate of the fast component and reduced the decay rate of the slow component. 4. The effect of niflumic acid on STIC amplitude was voltage-dependent and at -50 and +50 mV the IC50 values were 2.3 x 10(-6) M and 1.1 x 10(-6) M respectively (cf. 3.6 x 10(-6) M at -77 mV). 5. In K-free solutions at potentials of -50 mV and +50 mV, niflumic acid did not induce a dual exponential STIC decay but just increased the decay time constant at both potentials in a concentration-dependent manner. 6. Niflumic acid, in concentrations up to 5 x 10(-5) M, had no effect on spontaneous calcium-activated potassium currents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921628

  14. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

    Science.gov (United States)

    Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

    2017-07-01

    Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

  15. 腹主动脉瘤动脉壁血管平滑肌细胞增殖及凋亡的研究%Vascular smooth muscle cell proliferation and apoptosis of the aortic wall during the development of abdominal aortic aneurysm

    Institute of Scientific and Technical Information of China (English)

    李大勇; 车艳; 杨镛; 张强; 吕延伟

    2004-01-01

    目的研究腹主动脉瘤(abdominal aortic aneurysm,AAA)在发病不同时期动脉壁平滑肌细胞(smooth muscle cells,SMC)增殖与凋亡的改变. 方法建立大鼠AAA模型,分别于术后3 d、1、2、3、4周切取腹主动脉,应用原位DNA片段末端标记(TUNEL)和免疫组织化学方法检测腹主动脉壁中SMC凋亡和相关基因bcl-2、bax蛋白以及增殖细胞核抗原(PCNA)、α-血管平滑肌肌动蛋白(α-actin)的表达. 结果 TUNEL及PCNA表达高峰时段分别为术后2~3周和1周;术后3 d至1周凋亡细胞少于PCNA阳性SMC,2~4周多于PCNA阳性SMC且SMC数量明显减少;bcl-2与bax蛋白表达分别于术后1、3周达到峰值(P<0.01). 结论动脉壁SMC增殖和凋亡的失衡与AAA发病密切相关;bcl-2与bax基因参与了对AAA动脉壁中SMC凋亡的调控.

  16. 高浓度曲马朵通过内皮依赖与非依赖机制诱导家兔主动脉舒张%High-concentration tramadol-induced vasodilation in rabbit aorta is mediated by both endothelium-dependent and-independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Tijen KAYA; Sinan GURSOY; Batis KARADAS; Bulent SARAC; Haluk KAFALI; Ahmet Serdar SOYDAN

    2003-01-01

    AIM: The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic tings. METHODS: Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine (10-5 mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence and absence of endothelium, indomethacin (an inhibitor of cyclooxygenase), NG-nitro-L-arginine methyl ester (L-NAME, a specific inhibitor of nitric oxide synthase), glibenclamide (an inhibitor of ATP-sensitive potassium channels), tetraethylammonium chloride (TEA, an inhibitor of calcium-sensitive potassium channels), and naloxone (an antagonist of opioid receptors). RESULTS: Tramadol (10-4 mol/L and 3×10-4 mol/L) caused significant vasodilation in endothelium-intact and endothelium-denuded aortic rings (P<0.05). The relaxation response to tramadol was significantly greater in endothelium-intact rings than in endothelium-denuded rings. Pretreatment of aortic rings with indomethacin (10-5 mol/L), glibenclamide (10-5 mol/L), TEA (10-3 mol/L), and naloxone (10-4 mol/L) had no effect on the tramadol-induced relaxation. In endothelium-intact rings, L-NAME (10-4 mol/L) pretreatment caused marked inhibition of the relaxation induced by tramadol, but not endothelium-denuded rings. CONCLUSION: In the rabbit aorta, vascular relaxation induced by tramadol is due to both nitric oxide production from endothelium and a direct effect on smooth muscle.

  17. Aortic stenosis

    Science.gov (United States)

    ... Images Aortic stenosis Heart valves References Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/ ...

  18. Abdominal Aortic Aneurysm (AAA)

    Science.gov (United States)

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

  19. Disposable rabbit

    Science.gov (United States)

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  20. Disposal rabbit

    Science.gov (United States)

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  1. Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide.

    Science.gov (United States)

    Setnikar, I; Cereda, R; Pacini, M A; Revel, L; Makovec, F

    1989-09-01

    (+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.

  2. Analysis and Evaluation of the Comprehensive Experiment About Discharge of Aortic Nerve and Blood Pressure in Rabbits%家兔“减压神经放电与动脉血压调节”综合性实验的分析与评价

    Institute of Scientific and Technical Information of China (English)

    杨雪梅; 张冬梅; 王俊亚; 陈岩

    2016-01-01

    目的:加深学生对减压神经与动脉血压调节关系的理解与掌握,培养学生动手能力、观察能力和解决问题的能力。方法观察家兔在体减压神经传入冲动的发放特征及神经、体液因素对动脉血压变化与减压神经传入冲动发放的关系。结果减压神经放电幅度与心动周期中动脉血压的变化呈正相关;夹闭颈总动脉使减压神经放电增强;去甲肾上腺素使减压神经放电增强;乙酰胆碱使减压神经放电减弱。结论通过将学生实验过程中出现的问题以及解决方法进行归纳总结,提出实验注意事项与实验效果评价方法。%Objective To improve understanding of the students about the theory of discharge of aortic nerve on blood pressure adjustment, along with their hands-on ability, observational and problem-solving skills.Methods To observe the characteristics of Aortic Nerve Impulse in rabbits, along with the relations of neurohormonal factors and discharge of aortic nerve and blood pressure adjustment.Results There is a positive correlation between the amplitude of aortic nerve impulse and the changes of blood pressure in a cardiac cycle. The amplitude of Aortic nerve impulse was increased by clamping the common carotid artery or by norepinephrine. The amplitude of Aortic nerve impulse was decreased by acetylcholine.Conclusion We summarize the problems we encounter and solutions we use in doing these student experiments into experimental notes and evaluation methods which can guide us in future experiments.

  3. Photobiomodulation of vascular endothelial and smooth muscle cells in vitro with red laser light

    Science.gov (United States)

    Kipshidze, Nicholas; Keelan, Michael H., Jr.; Horn, Joseph B.; Nikolaychik, Victor

    1996-12-01

    Numerous reports suggest that low power red laser light (LPRLL) is capable of affecting cellular processes in the absence of significant thermal effect. The objective of the present study was to determine the effect of LPRLL on viability, growth, and attachment characteristics of rabbit and human aortic endothelial cells (EC) and smooth muscle cells (SMC) in vitro. All cell cultures were irradiated with single dose LPRLL using a He-Ne continuous wave laser with different energy densities. Assessment of effect on cell viability, growth, and attachment was performed utilizing Alamar Blue assay. Based upon our experiments, we conclude that: 1) stimulation and/or inhibition of cell growth and death can be obtained with LPRLL by varying the energy level, 2) LPRLL increases EC attachment, and 3) EC are more sensitive to photobiomodulation with LPRLL than SMC. These data may have significant importance leading to the establishment of new methods for phototherapy of atherosclerosis and restenosis.

  4. [Aortic aneurysm].

    Science.gov (United States)

    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. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  5. Effects of Temperature Changes on the Contractility of Isolated Small Intestinal Smooth Muscle in Rabbits%温度变化对家兔离体小肠平滑肌运动的影响

    Institute of Scientific and Technical Information of China (English)

    卡力比夏提·艾木拉江; 周玉东; 闫书平; 哈力旦阿合买提; 赵红琼

    2016-01-01

    In order to explore the influence of temperature changes on animal digestive tract smooth muscle ,the contractility of isolated rabbit small intestine (duodenum ,jejunum and ileum) were measured at different temperatures (39→32 ℃ ,32→39 ℃ ,39→42 ℃ and 42→39 ℃) using the biological signal processing system .The results showed that the contraction frequency of duo‐denum and jejunum was positively correlated with temperature changes between 39 and 32 ℃ , while the amplitude and tension of duodenum were negatively correlated with temperature chan‐ges .Only the contraction frequency of ileum was positively correlated with temperature changes between 39 and 32 ℃ .Changes of frequency ,amplitude and tension of duodenum between 39 and 42 ℃ were similar with those changes between 39 and 32 ℃ .However ,the contraction of jejunum and ileum was irregular .When the temperature was decreased from 42 to 39 ℃ ,the contraction of small intestine could not return to the condition in 39 ℃ .T he results suggested that the optimal bath temperature was 37 ℃ in contraction test of rabbit small intestine in vitro ,and the present results could be referenced to explore the disorder of gastrointestinal movement due to the change of environment temperature in animals .%为了探究温度变化对动物消化道平滑肌运动的影响,本试验用生物信号处理系统测定了浴槽不同温度(39→32℃、32→39℃、39→42℃和42→39℃)对家兔离体小肠各段(十二指肠、空肠、回肠)平滑肌运动的影响。结果显示,当温度在39和32℃之间变化时家兔离体十二指肠和空肠运动的收缩频率同温度变化呈正相关,而十二指肠收缩幅度和收缩张力同温度变化呈负相关,但回肠仅表现在收缩频率同温度变化呈正相关;当温度从39℃升高到42℃时,十二指肠的收缩频率、收缩幅度和收缩张力变化与温度在39和32℃之间变化情况相同,但

  6. Aortic Valve Disease

    Science.gov (United States)

    ... Tricuspid Valve Disease Cardiac Rhythm Disturbances Thoracic Aortic Aneurysm Pediatric and Congenital Heart Disease Heart abnormalities that are ... Transplantation End-stage Lung Disease Adult Lung Transplantation Pediatric Lung ... Aortic Aneurysm Aortic Valve Disease Overview The human heart has ...

  7. Expressions of associated proteins in vascular smooth muscle cells and infiltration of macrophages in elderly abdominal aortic aneurysms%老年人腹主动脉瘤血管平滑肌细胞相关蛋白表达及巨噬细胞浸润的病理学特点

    Institute of Scientific and Technical Information of China (English)

    庄世虹; 周洪莲; 黄敏; 聂斌

    2008-01-01

    Objective To investigate the pathological characteristics of the expressions of associated proteins in vascular smooth muscle cells and infiltration of macrophages in elderly abdominal aortic aneurysms. Methods HE stained slices, Van Gieson' s stained slices and immunohistochemical staining were applied to detect protein expression in the tissue sections of 15 cases of elderly abdominal aortic aneurysms and 6 cases of normal abdominal aorta. The protein expressions of α-smooth muscle actin, cathepsin B and CD68 were detected by immunohistochemical staining. Results Compared with normal abdominal aorta, the collagen content was higher in elderly abdominal aortic aneurysms [(9.3 ± 1.9) % vs. (5.3±1.8) %, P < 0.05]. The levels ofexpression of cathepsin B and CD68 were higher in elderly abdominal aortic aneurysms than those in normal abdominal aorta , but the level of expression of α-SMA was lower in elderly abdominal aorticaneurysms than that in normal abdominal aorta[(0.38±0.07) vs. (0.135=0.06), (0.51±0.12) vs.(0.01±0.01), (0.23±0.05) vs. (0.335±0.05) ,respectively, all P<0.05]. Conclusions Changes in the expression of associated proteins in vascular smooth muscle cells and infiltration of macrophages may participate in the vascular walls destruction in elderly abdominal aortic aneurysms.%目的 观察血管平滑肌细胞(VSMC)表达变化及巨噬细胞浸润在老年人腹主动脉瘤中的病理学特点. 方法 对15例老年人腹主动脉瘤与6例正常腹主动脉组织行HE染色、VanGieson法染色和免疫组织化学染色.用免疫组织化学染色检测α-平滑肌肌动蛋白(α-SMA)、组织蛋白酶B及CD68蛋白表达. 结果 老年人腹主动脉瘤病变处胶原容积百分比(9.3±1.9)%,较正常主动脉的(5.3±1.8)%增高(P<0.05).老年人腹主动脉瘤中组织蛋白酶B和CD68的表达增强分别为0.38+0.07和0.51±0.12,α-SMA表达减弱为0.23±0.05,与正常腹主动脉(分别为0.13±0.06和0.01±0.01,0.33±0.05)

  8. Bicuspid Aortic Valve

    Science.gov (United States)

    2006-08-01

    aortic valvular disease, endocarditis, ascending aortic aneurysm and aortic dissection.1-4 There is also an association of BAV with coarctation of...for aortic aneurysm , patients with BAV appear to have additional risks for aortic disease. Nistri et al.12 reported significant aortic root...Congenital heart disease in patients with Turner’s syndrome. Italian study group for Turner syndrome (ISGTS). J Pediatr 1998; 133:688-692. 7. Schmid

  9. Aortic Stenosis.

    Science.gov (United States)

    Bakaeen, Faisal G; Rosengart, Todd K; Carabello, Blase A

    2017-01-03

    This issue provides a clinical overview of aortic stenosis, focusing on screening, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  10. Inhibitory effects of Tabebuia impetiginosa inner bark extract on platelet aggregation and vascular smooth muscle cell proliferation through suppressions of arachidonic acid liberation and ERK1/2 MAPK activation.

    Science.gov (United States)

    Son, Dong-Ju; Lim, Yong; Park, Young-Hyun; Chang, Sung-Keun; Yun, Yeo-Pyo; Hong, Jin-Tae; Takeoka, Gary R; Lee, Kwang-Geun; Lee, Sung-Eun; Kim, Mi-Ran; Kim, Jeong-Han; Park, Byeoung-Soo

    2006-11-03

    The antiplatelet and antiproliferative activities of extract of Tabebuia impetiginosa inner bark (taheebo) were investigated using washed rabbit platelets and cultured rat aortic vascular smooth muscle cells (VSMCs) in vitro. n-Hexane, chloroform and ethyl acetate fractions showed marked and selective inhibition of platelet aggregation induced by collagen and arachidonic acid (AA) in a dose-dependent manner. These fractions, especially the chloroform fraction, also significantly suppressed AA liberation induced by collagen in [(3)H]AA-labeled rabbit platelets. The fractions, especially the chloroform fraction, potently inhibited cell proliferation and DNA synthesis induced by platelet derived growth factor (PDGF)-BB, and inhibited the levels of phosphorylated extracellular signal regulated kinase (ERK1/2) mitogen activated protein kinase (MAPK) stimulated by PDGF-BB, in the same concentration range that inhibits VSMC proliferation and DNA synthesis.

  11. Smooth magnetogenesis

    CERN Document Server

    Campanelli, L

    2016-01-01

    In the Ratra scenario of inflationary magnetogenesis, the kinematic coupling between the photon and the inflaton undergoes a nonanalytical jump at the end of inflation. Using smooth interpolating analytical forms of the coupling function, we show that such unphysical jump does not invalidate the main prediction of the model, which still represents a viable mechanism for explaining cosmic magnetization. Nevertheless, there is a spurious result associated with the nonanaliticity of the coupling, to wit, the prediction that the spectrum of created photons has a power-law decay in the ultraviolet regime. This issue is discussed using both semiclassical approximation and smooth coupling functions.

  12. Basal and Oxidative Stress–Induced Expression of Metallothionein Is Decreased in Ascending Aortic Aneurysms of Bicuspid Aortic Valve Patients

    Science.gov (United States)

    Phillippi, Julie A.; Klyachko, Ekaterina A.; Kenny, John P.; Eskay, Michael A.; Gorman, Robert C.; Gleason, Thomas G.

    2017-01-01

    Background Bicuspid aortic valve (BAV) is a heritable condition that has been linked by an unknown mechanism to a predisposition for ascending aortic aneurysm. Matrix metalloproteinases have been implicated in this predisposition. Metallothionein is a poorly characterized, metal-binding protein that regulates matrix metalloproteinases and is an antioxidant known to be upregulated under oxidative stress. Methods and Results To determine putative factors involved in the pathogenesis of aortic aneurysm in BAV patients, our first goal was to identify genes that are dysregulated in ascending aortic aneurysms of BAV patients compared with tricuspid aortic valve patients and nondiseased (control) donors. By microarray analysis (22 000 probe sets), 110 dysregulated genes were identified in BAV compared with tricuspid aortic valve patients and control donors; 8 were genes of the metallothionein family. Metallothionein gene expression and protein expression were significantly lower in aortic tissue and cultured aortic smooth muscle cells from BAV patients compared with control subjects. Matrix metalloproteinase-9 expression was increased in BAV aortic samples relative to controls. BAV aorta was more susceptible to oxidative stress, and induction of metallothionein under oxidative stress was reduced in BAV patients compared with control subjects. Conclusions These results demonstrate dysregulated metallothionein expression in ascending aortic smooth muscle cells of BAV patients that may contribute to an inadequate response to oxidative stress and provoke aneurysm formation. We hypothesize that metallothionein plays a pivotal role in the response of ascending aortic smooth muscle cells to oxidative stress cues normally involved in the maintenance of the extracellular matrix, including the regulation of matrix metalloproteinase expression. PMID:19398671

  13. Aortic valve bypass

    DEFF Research Database (Denmark)

    Lund, Jens T; Jensen, Maiken Brit; Arendrup, Henrik

    2013-01-01

    In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI...

  14. Quadricuspid Aortic Valve

    Directory of Open Access Journals (Sweden)

    Mehmet Taşar

    2013-03-01

    Full Text Available Quadricuspid aortic valve is an extremely rare congenital defect. Isolated form appears frequently. It is seen with aortic valve regurgitation in adulthood. This case report presents a rare clinical finding of an isolated quadricuspid aortic valve with aortic regurgitation in an 64-year-old female who was referred for cardiac evaluation due to newly identified murmur.

  15. Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models.

    Science.gov (United States)

    Milewicz, Dianna M; Prakash, Siddharth K; Ramirez, Francesco

    2017-01-14

    Thoracic aortic diseases, including aneurysms and dissections of the thoracic aorta, are a major cause of morbidity and mortality. Risk factors for thoracic aortic disease include increased hemodynamic forces on the ascending aorta, typically due to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease either disrupt smooth muscle cell (SMC) contraction or adherence to an impaired extracellular matrix, or decrease canonical transforming growth factor beta (TGF-β) signaling. Paradoxically, TGF-β hyperactivity has been postulated to be the primary driver for the disease. More recently, it has been proposed that the response of aortic SMCs to the hemodynamic load on a structurally defective aorta is the primary driver of thoracic aortic disease, and that TGF-β overactivity in diseased aortas is a secondary, unproductive response to restore tissue function. The engineering of mouse models of inherited aortopathies has identified potential therapeutic agents to prevent thoracic aortic disease.

  16. Smoothed Invariants

    CERN Document Server

    Dye, H A

    2011-01-01

    We construct two knot invariants. The first knot invariant is a sum constructed using linking numbers. The second is an invariant of flat knots and is a formal sum of flat knots obtained by smoothing pairs of crossings. This invariant can be used in conjunction with other flat invariants, forming a family of invariants. Both invariants are constructed using the parity of a crossing.

  17. Isoform-specific Regulation of Sodium pump α-subunit Gene Expression i n Aortic Smooth Muscle Cell of 1-kidney-1-clip Hypertensive Rats%“一肾一夹”高血压大鼠动脉平滑肌细胞钠泵α亚单位的基因表达

    Institute of Scientific and Technical Information of China (English)

    原卫清; 王颢; 吕卓人

    2001-01-01

    Objective To investigate the gene expression of sodium pump α-subunit in aortic smooth muscle of 1-kidney-1-clip (1k1c) hypertensive rats.  Methods 1k1c hypertensive rats were prepared by partially ligating the left renal artery and removing the right kidney. 4 weeks later, all the rats were killed and sodium pump α1- , α2-, and α3-subunit in aortic smooth muscles were detected with reverse transcription p ol ymerase chain reaction (RT-PCR) method and immunohistochemical assay at both mR NA and protein levels, respectively.  Resulsts Changes in the expression of sodi um pump α-subunit gene were found in aortic smooth muscles of 1k1c hypertensiv e rats: α1-su bunit increased at both mRNA protein levels, while α2- and α3-subunits r emained without changes.  Conclusions There were great changes in the gene expression of so dium pump α-subunit in aor tic smooth muscles of 1k1c hypertensive rats, which might be related to the development of hypertension in this hypertensive model.%目的 探讨“一肾一夹(1k1c)”高血压大鼠动脉平滑肌细胞钠泵α亚单位各异构体基 因表达的改变,为高血压发病机制的深入研究提供理论及实验依据。方法 分别应用分子生物学 RT-PCR及免疫组化技术,探讨1k1c高血压大鼠动脉平滑肌细胞钠泵α1、α2及α3亚单位mR NA及蛋白 水平基因表达的改变。结果 1k1c高血压大鼠动脉平滑肌细胞钠泵α亚单位基因表达发生改变: 无论在mRNA或蛋白水平,α1亚单位表达增强,而α2与α3亚单位表达无改变。结论 1k1c高血压大鼠动脉平滑肌细胞钠泵α亚单位基因表达发生改变,这种 改变可能参与了该模型的血压升高 机制。

  18. Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo

    Institute of Scientific and Technical Information of China (English)

    Hong-fang LI; Long-de WANG; Song-yi QU

    2004-01-01

    AIM: To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-β estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats. METHODS: (1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb's solution, and then isometric tension was measured. (2) Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4(1) Similar to 17-β estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips.Incubation with Nω-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2,and shift their cumulative concentration-response curves rightward. (2) MAP in OVX rats was significantly higher compared with that of SHAM rats. However, after chronically treatment with genistein or 17-β estradiol for 21 d the baseline MAP in OVX rats was reduced significantly. CONCLUSIONS: (1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2+ influx through calcium channels in a noncompetitive manner and Ca2+ release from intracellular store induced by NA. (2) Administration of genistein or 17-β estradiol can chronically decrease MAP in OVX rats.

  19. Efeitos da atorvastatina, fluvastatina, pravastatina e simvastatina sobre a função endotelial, a peroxidação lipídica e a aterosclerose aórtica em coelhos hipercolesterolêmicos Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    Paulo Afonso Ribeiro Jorge

    2005-04-01

    wall of hypercholesterolemic rabbits after adjusting the dosages of those statins to reduce total serum cholesterol levels to similar values. METHODS: Male rabbits were divided into the following 6 groups of 10 animals (n=10: 1 GH (control - hypercholesterolemic animals; 2 GA - atorvastatin; 3 GF - fluvastatin; 4 GP - pravastatin; 5 GS - simvastatin; and 6 GN - normal. The animals were fed a standard food preparation enriched with 0.5% cholesterol and 2% coconut oil for 45 days. Fifteen days after beginning the experiment, atorvastatin, fluvastatin, pravastatin and simvastatin were administered for 15 days through gavage, and the dosages were adjusted to obtain similar cholesterol values in each group. At the end of the experiment, a blood sample was withdrawn for determining total cholesterol and separating the lipoproteins, and a segment of the thoracic aorta was removed to be used for studying endothelial function and lipid peroxidation, and for measuring aortic atherosclerosis in histological sections. RESULTS: The statins significantly reduced total serum cholesterol levels, LDL-cholesterol levels, and aortic atherosclerosis. The MDA content was also significantly reduced in native and oxidized LDL, as well as in the arterial wall. Endothelium-dependent relaxation was significantly greater in the treated group compared with that in the hypercholesterolemic group. CONCLUSION: The statins, at dosages adjusted, had a significant and similar effect in reducing lipid peroxidation in native and oxidized LDL-C and in arterial walls, in decreasing aortic atherosclerosis, and in reverting endothelial dysfunction.

  20. Gender differences in abdominal aortic aneurysms.

    Science.gov (United States)

    Hannawa, Kevin K; Eliason, Jonathan L; Upchurch, Gilbert R

    2009-01-01

    Abdominal aortic aneurysms (AAAs) comprise the tenth leading cause of death in Caucasian males 65 to 74 years of age and accounted for nearly 16,000 deaths overall in 2000. Therefore, understanding the pathophysiology of AAAs is an important undertaking. Clinically, multiple risk factors are associated with the development of AAAs, including increasing age, positive smoking history, and hypertension. Male gender is also a well-established risk factor for the development of an AAA, with a 4:1 male to female ratio. The reason for this gender disparity is unknown. The pathogenesis of AAAs formation is complex and multifactorial. Histologically, AAAs are characterized by early chemokine-driven leukocyte infiltration into the aortic wall. Subsequent destruction of elastin and collagen in the media and adventitia ensues owing to excessive local production of matrix-degrading enzymes and is accompanied by smooth muscle cell loss and thinning of the aortic wall. At present, no medical therapies are available to treat patients with aortic aneurysms, using only the crude measurement of aortic diameter as a threshold for which patients must undergo life-threatening and costly surgery. Defining the early mechanisms underlying gender-related differences in AAA formation is critical as understanding differences in disease patterns based on gender may allow us to develop new translational approaches to the prevention and treatment of patients with aortic aneurysms.

  1. Expression of GRP78 and caspase-12 in aortic vascular smooth muscle cells of hypertension rats and effects of enalapril on vascular remodeling%高血压大鼠血管平滑肌细胞GRP78和caspase-12表达的变化及依那普利的干预作用

    Institute of Scientific and Technical Information of China (English)

    郭丽; 赵连友; 刘静; 张志敏; 李雪; 丁璐

    2013-01-01

    AIM: To examine the effect of endoplasmic reticulum stress (ERS) on vascular remodeling induced by hypertension and to observe the effects of enalapril on the expressions of the correlation factors GRP78 and caspase-12 in vascular smooth muscle cells (VSMCs) and their relationship with vascular changes. METHODS: Forty adult male SD rats were randomly divided into sham operation group, sham + Ena group, AAB group and the AAB + Ena group. Four weeks later, MBP was measured through carotid artery incubation, the aortic media thickness was measured by image analyses software and the expressions of GRP78 and caspase-12 in the vascular smooth muscle cells were examined by immunohisto-chemistry. RESULTS: MAP of AAB group rats was significantly higher than those of rats in sham operation group, sham + Ena group and AAB + Ena group (P < 0. 05). The aortic media thickness of AAB group rats was significantly thicker than those of rats in sham operation group, sham + Ena group and the AAB + Ena group (P <0. 05). The expressions of GRP78 and caspase-12 of AAB group rats were significantly higher than those of rats in sham group, sham +Ena group and AAB +Ena group. CONCLUSION: High blood pressure resulting from abdominal aortic bounding causes endoplasmic reticulum stress response of vascular smooth muscle cells. Enalapril may exert some protective effects on VSMCs by inhibiting the endoplasmic reticulum stress via downregulation of the expression of caspase-12.%目的:观察高血压大鼠动脉血管平滑肌细胞(VSMCs)内质网应激(ERS)相关因子葡萄糖调节蛋白78(GRP78)和半胱氨酸门冬氨酸特异性蛋白酶12(caspase-12)表达的变化,并探讨高血压时VSMCs中ERS的分子机制,以及依那普利(enalapril,Ena)对血管重构的影响.方法:将40只健康雄性SD大鼠随机分为4组,即假手术(sham)组、sham+ Ena组,腹主动脉缩窄术(AAB)组及AAB+ Ena组,每组10只.4周后,通过颈动脉插管法测定大鼠血压和利用图像分析系

  2. Aortic Annular Enlargement during Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Selman Dumani

    2016-09-01

    Full Text Available 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.

  3. Nuclear factor of activated T cells c1 mediates p21-activated kinase 1 activation in the modulation of chemokine-induced human aortic smooth muscle cell F-actin stress fiber formation, migration, and proliferation and injury-induced vascular wall remodeling.

    Science.gov (United States)

    Kundumani-Sridharan, Venkatesh; Singh, Nikhlesh K; Kumar, Sanjay; Gadepalli, Ravisekhar; Rao, Gadiparthi N

    2013-07-26

    Recent literature suggests that cyclin-dependent kinases (CDKs) mediate cell migration. However, the mechanisms were not known. Therefore, the objective of this study is to test whether cyclin/CDKs activate Pak1, an effector of Rac1, whose involvement in the modulation of cell migration and proliferation is well established. Monocyte chemotactic protein 1 (MCP1) induced Pak1 phosphorylation/activation in human aortic smooth muscle cells (HASMCs) in a delayed time-dependent manner. MCP1 also stimulated F-actin stress fiber formation in a delayed manner in HASMCs, as well as the migration and proliferation of these cells. Inhibition of Pak1 suppressed MCP1-induced HASMC F-actin stress fiber formation, migration, and proliferation. MCP1 induced cyclin D1 expression as well as CDK6 and CDK4 activities, and these effects were dependent on activation of NFATc1. Depletion of NFATc1, cyclin D1, CDK6, or CDK4 levels attenuated MCP1-induced Pak1 phosphorylation/activation and resulted in decreased HASMC F-actin stress fiber formation, migration, and proliferation. CDK4, which appeared to be activated downstream of CDK6, formed a complex with Pak1 in response to MCP1. MCP1 also activated Rac1 in a time-dependent manner, and depletion/inhibition of its levels/activation abrogated MCP1-induced NFATc1-cyclin D1-CDK6-CDK4-Pak1 signaling and, thereby, decreased HASMC F-actin stress fiber formation, migration, and proliferation. In addition, smooth muscle-specific deletion of NFATc1 led to decreased cyclin D1 expression and CDK6, CDK4, and Pak1 activities, resulting in reduced neointima formation in response to injury. Thus, these observations reveal that Pak1 is a downstream effector of CDK4 and Rac1-dependent, NFATc1-mediated cyclin D1 expression and CDK6 activity mediate this effect. In addition, smooth muscle-specific deletion of NFATc1 prevented the capacity of vascular smooth muscle cells for MCP-1-induced activation of the cyclin D1-CDK6-CDK4-Pak1 signaling axis, affecting

  4. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections.

    Science.gov (United States)

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

    2016-03-01

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

  5. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  6. Aortic dissection (image)

    Science.gov (United States)

    Aortic dissection is a condition in which there is bleeding into and along the wall of the aorta (the ... the inner wall of the artery. Although aortic dissection can affect anybody, it is most often seen ...

  7. Abdominal aortic aneurysm

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000162.htm Abdominal aortic aneurysm To use the sharing features on this page, ... blood to the abdomen, pelvis, and legs. An abdominal aortic aneurysm occurs when an area of the aorta becomes ...

  8. Aortic growth rates in chronic aortic dissection

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, A.M. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States)]. E-mail: ainekell@med.umich.edu; Quint, L.E. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States); Nan, B. [School of Public Health, University of Michigan, Ann Arbor, Michigan (United States); Zheng, J. [School of Public Health, University of Michigan, Ann Arbor, Michigan (United States); Cronin, P. [Department of Radiology, Division of Thoracic Radiology, University of Michigan Medical Center (United States); Deeb, G.M. [Division of Cardiac Surgery, University of Michigan Medical Center (United States); Williams, D.M. [Division of Vascular Interventional Imaging, University of Michigan Medical Center (United States)

    2007-09-15

    Aim: To determine and compare rates of descending aortic enlargement and complications in chronic aortic dissection with and without a proximal aortic graft. Methods and materials: Fifty-two patients with dissection involving the descending aorta and who had undergone at least two computed tomography (CT) examinations at our institution between November, 1993 and February, 2004 were identified, including 24 non-operated patients (four type A, 20 type B) and 28 operated patients (type A). CT examinations per patient ranged from two to 10, and follow-up ranged from 1-123 months (mean 49 months, median 38.5 months). On each CT image, the aortic short axis (SA), false lumen (FL), and true lumen (TL) diameters were measured at the longitudinal midpoint of the dissection and at the point of maximum aortic diameter. Complications were tabulated, including aortic rupture and aortic enlargement requiring surgery. Results: For non-operated patients, the midpoint and maximum point SA, TL, and FL diameters increased significantly over time. For operated patients, the midpoint and maximum point SA and FL diameters increased significantly over time. In both groups, aortic enlargement was predominantly due to FL expansion. Diameter increases in non-operated patients were significantly larger than those in operated patients. The rate of change in aortic diameter was constant, regardless of aortic size. Four non-operated and six operated patients developed aortic complications. Conclusions: In patients with a dissection involving the descending thoracic aorta, the FL increased in diameter over time, at a constant rate, and to a greater degree in non-operated patients (mostly type B) compared with operated patients (all type A)

  9. Adventitial vasa vasorum arteriosclerosis in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Hiroki Tanaka

    Full Text Available Abdominal aortic aneurysm (AAA is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac; further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease.

  10. The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm

    OpenAIRE

    Jiaze Li; Smriti Murali Krishna; Jonathan Golledge

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of funct...

  11. Effects of Dian Kuang Meng Xing Tang on the proliferation of vascular smooth muscle cells in atherosclerosis rabbits%动脉粥样硬化模型兔血管平滑肌细胞增殖与癫狂梦醒汤的干预

    Institute of Scientific and Technical Information of China (English)

    韩凤丽; 于铭权

    2012-01-01

    背景:现代临床研究表明癫狂梦醒汤能够治疗神经官能症、更年期综合征、癔病、老年痴呆等精神系统疾病.目的:观察癫狂梦醒汤对动脉粥样硬化模型兔血管平滑肌细胞增殖的影响.方法:将32只日本大耳白兔随机分成空白对照组、模型组、癫狂梦醒汤组、辛伐他汀组,分别给予普通饲料、高脂饲料、高脂饲料+癫狂梦醒汤、高脂饲料+辛伐他汀进行干预,喂养至第12周末.结果与结论:喂养高脂饲料成功建立动脉粥样硬化模型,模型组有严重的动脉粥样硬化病理改变,增殖细胞核抗原、血小板源生长因子B蛋白表达明显升高,平滑肌细胞呈合成型改变;癫狂梦醒汤组及辛伐他汀组动脉粥样硬化病变明显减轻,增殖细胞核抗原、血小板源生长因子B蛋白表达明显下降(P < 0.01),平滑肌细胞接近"收缩型"改变.结果可见癫狂梦醒汤可抑制血管平滑肌细胞增殖,延缓动脉粥样硬化发生发展,这一作用可能是通过抑制增殖细胞核抗原、血小板源生长因子B蛋白表达来实现的.%BACKGROUND: Modern clinical studies have shown that Dian Kuang Meng Xing Tang (awaken from the dream of madness decoction) has remedial effects on neurosis, menopausal syndrome, hysteria, dementia and other mental disorders.OBJECTIVE: To investigate the effects of Dian Kuang Meng Xing Tang on the proliferation of vascular smooth muscle cells in atherosclerosis rabbits.METHODS: A total of 32 Japan big-ear white rabbits were randomly divided into normal control group, model group, Dian Kuang Meng Xing Tang group and Simvastatin group; the corresponding rabbits in each group were fed with normal diet, high fat diet, high fat diet+ Dian Kuang Meng Xing Tang and high fat diet+Simvastatin for 12 weeks, respectively.RESULTS AND CONCLUSION: The atherosclerosis model was successfully established with high fat diet. There was a severe pathological lesion of atherosclerosis in the

  12. Mast Cells in Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Shi, Guo-Ping; Lindholt, Jes Sanddal

    2013-01-01

    Mast cells (MCs) are proinflammatory cells that play important roles in allergic responses, tumor growth, obesity, diabetes, atherosclerosis, and abdominal aortic aneurysm (AAA). Although the presence and function of MCs in atherosclerotic lesions have been thoroughly studied in human specimens...... neighboring cells, degrade extracellular matrix proteins, process latent bioactive molecules, promote angiogenesis, recruit additional inflammatory cells, and stimulate vascular cell apoptosis. These activities associate closely with medial elastica breakdown, medial smooth-muscle cell loss and thinning...

  13. Rabbit hematology.

    Science.gov (United States)

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  14. 氧化低密度脂蛋白诱导主动脉平滑肌细胞胆固醇酯聚集和凋%Oxidized-LDL Leads to Cholesteryl Ester Accumulation and A poptosis in Porcine Aortic Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    袁中华; 杨永宗; 杨小毅

    2002-01-01

    Both cellular cholesterol metabolism imbalance and apoptosis are related to th e development of atherosclerosis. To investigate the relationship between the ce llular cholesterol metabolism and apoptosis, the porcine aortic smooth muscle ce lls were cultured with medium 199 containing 15 mg/L oxidized low density lipo protein (Ox-LDL) for 72 h, the ratio of cellular cholesteryl ester to total cholesterol increased from 26.2% to 64.1%, and Ox-LDL induced accumulation o f cellular ch olesteryl ester in a concentration dependent manner in the cells. It indicated t hat the vascular smooth muscle cells had transformed to foam cells. In addition, cells incubated with oxidized low density lipoprotein had characteristic of apo ptosis, as determined by fluorescence microscope, laser scanning confocal micros cope and flow cytometry. From this findings, it was speculated that the inducti on of apoptosis may be related to the raise of the ratio of cellular cholesteryl este r to total cholesterol besides oxidation of low density lipoprotein in vascular smooth muscle cells.%细胞内胆固醇代谢的失衡和细胞凋亡都与动脉粥样硬化的发生有关.为了研究两者之间的关系,我们把猪的主动脉平滑肌细胞与15 mg/L氧化低密度脂蛋白共同孵育 72 h,发现细胞内胆固醇酯与总胆固醇的比值由26.2%增加到64.1%,并且细胞内胆固醇酯的积聚有剂量依赖关系,表明细胞已经转化为平滑肌源性的泡沫细胞.另外,使用荧光显微镜、激光共聚焦显微镜和流式细胞仪分别发现,与氧化低密度脂蛋白共孵育的细胞有典型的凋亡形态改变.从实验可以推测,由氧化低密度脂蛋白诱导的平滑肌细胞凋亡,除了低密度脂蛋白氧化的因素外,也可能与细胞内胆固醇酯与总胆固醇的比值升高有关.

  15. Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-α and IGF-II.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Escribano, Óscar; Perdomo, Liliana; Otero, Yolanda F; García-Gómez, Gema; Fernández, Silvia; Beneit, Nuria; Benito, Manuel

    2013-07-01

    To assess the role of insulin receptor (IR) isoforms (IRA and IRB) in the proliferation of vascular smooth muscle cells (VSMCs) involved in the atherosclerotic process, we generated new VSMC lines bearing IR (wild-type VSMCs; IRLoxP(+/+) VSMCs), lacking IR (IR(-/-) VSMCs) or expressing IRA (IRA VSMCs) or IRB (IRB VSMCs). Insulin and different proatherogenic stimuli induced a significant increase of IRA expression in IRLoxP(+/+) VSMCs. Moreover, insulin, through ERK signaling, and the proatherogenic stimuli, through ERK and p38 signaling, induced a higher proliferation in IRA than IRB VSMCs. The latter effect might be due to IRA cells showing a higher expression of angiotensin II, endothelin 1, and thromboxane 2 receptors and basal association between IRA and these receptors. Furthermore, TNF-α induced in a ligand-dependent manner a higher association between IRA and TNF-α receptor 1 (TNF-R1). On the other hand, IRA overexpression might favor the atherogenic actions of IGF-II. Thereby, IGF-II or TNF-α induced IRA and IGF-I receptor (IGF-IR) overexpression as well as an increase of IRA/IGF-IR hybrid receptors in VSMCs. More importantly, we observed a significant increase of IRA, TNF-R1, and IGF-IR expression as well as higher association of IRA with TNF-R1 or IGF-IR in the aorta from ApoE(-/-) and BATIRKO mice, 2 models showing vascular damage. In addition, anti-TNF-α treatment prevented those effects in BATIRKO mice. Finally, our data suggest that the IRA isoform and its association with TNF-R1 or IGF-IR confers proliferative advantage to VSMCs, mainly in response to TNF-α or IGF-II, which might be of significance in the early atherosclerotic process.

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

    Science.gov (United States)

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

    2013-01-01

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

  17. 虎杖提取物对小鼠肠运动功能和家兔离体肠平滑肌的影响%The Effects of Polygonum Cuspidatum Extract on Intestinal Motor Function in Mice and Rabbits Intestinal Smooth Muscle in Vitro

    Institute of Scientific and Technical Information of China (English)

    门瑛璇; 王薇

    2009-01-01

    Objective: Observation of Polygonum cuspidatum extract on normal mice and mice constipation, intestinal motor function, explore its removal;Observation of Polygonum cnspidatum extract rabbit intestinal smooth muscle in vitro, and to investigate the effect of its removal mechanism. Methods : In vivo method of large, medium and small three doses of Polygonum cuspidatum solution of normal mice and mice constipation, intestinal motor function; In vitro methods used to observe large,3 small dose of Polygonum cuspidatum solution of rabbit intestinal smooth muscle in vitro effects. Results: large,3 small dose of Polygonum cuspidatum solution could improve constipation normal mice and mice intestine ink pro-mote percentage constipation can be shortened first mouse droppings containing ink latency,increase within six hours to collect stool samples containing ink particles total;Polygonum euspidatum extract on the rabbit intestinal smooth muscle in vitro and the role of Polygonum cuspidatum extract concentration and dose-related, dose Huzhang solution (0. 2mL) can significantly promote rabbits in vitro intestinal smooth muscle contraction, and confrontation by atropine, Epinephrine-in-duced intestinal muscle relaxation to acetylcholine and histamine, barium chloride, phentolamine caused by intestinal mus-cle contraction performance facilitating role. Conclusion: Large, medium and small three doses of Polygonum cuspidatum solution of normal mice and mice constipation, peristalsis of the small intestine were promoted; Polygonum cuspidatum ex-tract promotes peristalsis,may be Polygonum cuspidatum extract direct access this role role in intestinal smooth muscle cells caused.%目的;观察虎杖提取物对正常小鼠和便秘小鼠大、小肠运动功能及对家兔离体肠平滑肌的影响,并探讨其作用杌理.方法:采用在体方法观察大、中、小3个剂量的虎杖提取物对正常小鼠和便秘小鼠大、小肠运动功能的影响;采用离

  18. Relative Smooth Topological Spaces

    Directory of Open Access Journals (Sweden)

    B. Ghazanfari

    2009-01-01

    Full Text Available In 1992, Ramadan introduced the concept of a smooth topological space and relativeness between smooth topological space and fuzzy topological space in Chang's (1968 view points. In this paper we give a new definition of smooth topological space. This definition can be considered as a generalization of the smooth topological space which was given by Ramadan. Some general properties such as relative smooth continuity and relative smooth compactness are studied.

  19. Effects of oral administration of tripeptides derived from type I collagen (collagen tripeptide) on atherosclerosis development in hypercholesterolemic rabbits.

    Science.gov (United States)

    Tang, Lihua; Sakai, Yasuo; Ueda, Yoshimichi; Katsuda, Shogo

    2015-05-01

    Digestion of type I collagen with a collagenase-type protease yields a collagen tripeptide (Ctp) fraction comprising Gly-X-Y sequences that exhibit diverse biological activities. We previously demonstrated that Ctp inhibits the proliferation and migration of cultured aortic smooth muscle cells (SMCs) in vitro. These cells contribute to the pathogenesis of atherosclerosis and other cardiovascular diseases. In order to evaluate the effects of Ctp on atherosclerosis development in vivo, here we used the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit model of familial hypercholesterolemia to determine the effects of oral administration of Ctp for three months. Ctp induced a significant decrease in the area occupied by atherosclerotic plaques in the aorta and in the level of total serum cholesterol. The components of atherosclerotic plaques underwent distinct changes, including reduction in the populations of macrophages and SMCs and a significant decrease in the proportion of macrophages to SMCs. Ctp administration decreased the number of cells in plaques that expressed proliferating cell nuclear antigen and the number of cells with oxidative damage to DNA as indicated by 8-hydroxy-2'-deoxyguanine detection. These findings are the first to define the mechanism underlying the inhibitory effects of Ctp on atherosclerosis development in hypercholesterolemic rabbits, and suggest that Ctp provides an effective therapy for treating atherosclerosis.

  20. Transforming growth factor-β and abdominal aortic aneurysms.

    Science.gov (United States)

    Wang, Yutang; Krishna, Smriti; Walker, Philip J; Norman, Paul; Golledge, Jonathan

    2013-01-01

    Abdominal aortic aneurysms (AAAs) are common problems in aged people which can be associated with severe complications including aortic rupture and death. Transforming growth factor-β (TGFβ) has been implicated as causative in the development of thoracic aortic aneurysms (TAAs). In contrast, current evidence suggests TGFβ inhibits AAA development. Polymorphisms in the TGFβ signaling components are associated with AAA in some human population studies. In experimental animals TGFβ protects against AAA formation, progression and rupture. In animal models of AAA TGFβ decreases aortic inflammatory cell infiltration, extracellular matrix degradation, and vascular smooth muscle cell apoptosis, all factors implicated in AAA pathogenesis. The TGFβ signaling pathway may provide a therapeutic target for AAA although better clarity is needed regarding the distinct roles of TGFβ in TAA and AAA.

  1. Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables

    DEFF Research Database (Denmark)

    Hansen, B F; Mortensen, A; Hansen, J F

    1994-01-01

    estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19......-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity...... was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable....

  2. Tobacco constituents are mitogenic for arterial smooth-muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, C.G.; Hajjar, D.P.; Hefton, J.M.

    1985-07-01

    Tobacco glycoprotein (TGP) purified from flue-cured tobacco leaves, tar-derived material (TAR), the water soluble, nondialyzable, delipidized extract of cigarette smoke condensate, rutin-bovine serum albumin conjugates, quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells, but not adventitial fibroblasts. The mitogenicity appears to depend on polyphenol epitopes on carrier molecules. Ellagic acid, another plant polyphenol, inhibited arterial smooth-muscle proliferation. These results suggest that a number of ubiquitous, plant-derived substances may influence smooth-muscle cell proliferation in the arterial wall.

  3. Conservative management of chronic aortic dissection with underlying aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Mohammad Yusuf Beebeejaun

    2013-01-01

    Full Text Available 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, infiltrates or pleural effusions. Other tion. 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.

  4. Rhythmic Aortic Contractions Induced by Electrical Stimulation In Vivo in the Rat.

    Directory of Open Access Journals (Sweden)

    Niaz Sahibzada

    Full Text Available For over a century, the behavior of the aorta and other large arteries has been described as passive elastic tubes in which no active contraction occurs in the smooth muscle wall. In response to pulsatile pressure changes, the vessels undergo a 'passive' elastic dilatation-contraction cycle, described as a "Windkessel" effect. However, Mangel and colleagues have presented evidence that is contrary to this view. They reported that in the rabbit, the aorta undergoes rhythmic 'active' (contraction during the cardiac cycle; but these findings have been largely ignored. In the present study, we observed spontaneous contractions in synchrony with the heartbeat in another species (rat. In addition we demonstrate that aorta contractions are of neurogenic origin. Electrical stimulation of the aorta evoked contractions that occur at a rate that is in the range of the animal's heartbeat and are suppressed by tetrodotoxin and the alpha-adrenergic receptor blocker, phentolamine. Altogether, these findings indicate that aortic contractions are under neural control from the heart.

  5. Poly-ε-caprolactone mesh as a scaffold for in vivo tissue engineering in rabbit esophagus

    DEFF Research Database (Denmark)

    Diemer, Pernille; Markoew, S.; Le, Dang Quang Svend

    2015-01-01

    Repair of long-gap esophageal atresia is associated with a high degree of complications. Tissue engineering on a scaffold of a bioresorbable material could be a solution. The aim of the present study was to investigate the in vivo tissue engineering of smooth muscle cells and epithelium on a poly......-ε-caprolactone mesh in rabbit esophagus. Twenty female rabbits had a window of 0.6 × 1 cm cut in the abdominal part of the esophagus. The defect was covered with a poly-ε-caprolactone mesh. The rabbits were killed on postoperative day 28–30, and mesh with surrounding esophagus was removed for histological examination....... Fifteen rabbits survived the trial period. Six had no complications and had the mesh in situ. They all had ingrowth of epithelial and smooth muscle cells and an almost completely degraded mesh. Nine rabbits developed pseudo-diverticula. It proved possible to engineer both epithelial and smooth muscle...

  6. Viral infections of rabbits.

    Science.gov (United States)

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Preliminary research on myosin light chain kinase in rabbit liver

    Institute of Scientific and Technical Information of China (English)

    Bin Ren; Hua-Qing Zhu; Zhao-Feng Luo; Qing Zhou; Yuan Wang; Yu-Zhen Wang

    2001-01-01

    AIM: To study preliminarily the properties of myosin light chain kinase (MLCK) in rabbit liver. METHODS: The expression of MLCK was detected by reverse transcription-polymerase chain reaction (RT-PCR);the MLCK was obtained from rabbit liver, and its activity was analyzed by γ-32P incorporation technique to detect the phosphorylation of myosin light chain. RESULTS: MLCK was expressed in rabbit liver, and the activity of the enzyme was similar to rabbit smooth muscle MLCK, and calmodulin-dependent. When the concentration was 0.65 mg-L-1, the activity was at the highest level. CONCLUSION: MLCK expressed in rabbit liver may catalyze the phosphorylation of myosin light chain, which may play important roles in the regulation of hepatic cell functions.

  8. 硫化氢对正常及自发性高血压大鼠主动脉平滑肌细胞PCNA和p-ERK蛋白表达的影响%Effect of hydrogen sulfide on the expression of PCNA and p-ERK in the aortic smooth muscle cells of normal rats and spontaneous hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    金红芳; 田悦; 闫辉; 唐朝枢; 杜军保

    2008-01-01

    目的 研究硫化氢(hydrogen sulfide,H2S)对正常大鼠及自发性高血压大鼠(spontaneous hypertensive rat,SHR)主动脉平滑肌细胞(aortic smooth muscle cell,ASMC)增殖的影响.方法 分别将正常大鼠及SHR主动脉平滑肌细胞分为实验组和对照组,实验组中分别加入浓度为(10-5~10-3) mol·L-1 H2S供体的硫氢化钠(sodium hydrosulfide, NaHS)或浓度为(2~10)mmol·L-1胱硫醚-γ-裂解酶抑制剂的炔丙基甘氨酸(DL-propargylglycine,PPG),对照组加入等体积的生理盐水,分别以蛋白质印迹法观察6、12、18和24 h时间点的平滑肌细胞中细胞增殖核抗原(PCNA)和磷酸化的细胞外信号调节激酶(p-ERK)蛋白表达情况.结果 NaHS对正常大鼠ASMC增殖及p-ERK蛋白表达无影响.PPG显著促进正常大鼠ASMC增殖及p-ERK蛋白表达.NaHS显著抑制SHR的ASMC增殖及p-ERK蛋白表达.PPG显著促进SHR的ASMC增殖及p-ERK蛋白表达.结论 内源性H2S下调可促进正常大鼠及SHR的ASMC增殖,而外源性补充H2S可抑制SHR的ASMC异常增殖,ERK信号途径可能介导H2S抑制ASMC增殖的分子机制.

  9. Effects of Porphyromonas gingivalis on expression of IL-6 and IL-1 β in rabbit vascular smooth muscle cells%牙龈卟啉单胞菌对兔血管平滑肌细胞分泌IL-1β、IL-6的影响

    Institute of Scientific and Technical Information of China (English)

    赵瑜敏; 张明珠; 税艳青; 陈立忠; 崔平平; 雷雅燕

    2012-01-01

    目的:观察牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)上清液对体外培养的兔血管平滑肌细胞分泌IL-1β、IL-6的影响.方法:组织块法培养兔腹主动脉血管平滑肌细胞,并对其细胞来源进行鉴定.用4.3×106 CFU/mL的Pg上清液刺激细胞12、24、48h后,通过ELISA检测IL-1β、IL -6的水平;同时用RT-PCR检测其mRNA表达的情况.结果:Pg上清液刺激24h和48 h时能促进血管平滑肌细胞分泌IL-6,分别与同一时间点的对照组相比差异均有统计学意义(P<0.05),而且24 h时,IL-6表达最强,而IL-1β的表达最低,明显低于相同时间的对照组和其他时间点的实验组(P<0.05).RT-PCR检测显示,4.3×106 CFU/mL的Pg 上清刺激血管平滑细胞12、24、48 h后细胞内均有IL - 1β、IL-6的基因表达,在24 h时,血管平滑肌细胞的IL-Iβ基因表达减少,而IL-6基因表达增加.结论:Pg上清液可促进细胞合成和分泌IL-6,在动脉粥样硬化的发生发展过程中可能发挥一定作用.%AIM; To investigate the effects of Porphyromonas gingivalis on the expression of IL-6 and IL-1β in rabbit vascular smooth muscle cells (CSMCs). METHODS; Rabbit VSMCs were derived from primary cluture of rabbit abdominal aorta. VSMCs were stimulated with P. gingivalis supernatant. At 12 h, 24 h and 48 h of stimulation, VSMCs cell culture medium was subjected to ELISA for IL-6 and IL-1β protein measurement. RNA was extracted from the cells and RT-PCR was conducted to determine IL-6 and IL-1 β gene expression. RESULTS; Exposure to P. gingivalis supernatant significantly increased gene expression and protein secretion of IL-6 in VSMCs ( P < 0. 05 ) . However, IL-1β expression was significantly decreased at 24 h of P. gingivalis exprosure ( P < 0. 05 ) , although a slight increase was observed at 48 h. CONCLUSION; P. gingivalis supernatant shows different effects on IL-6 and IL-1β expression in VSMCs. P. gingivalis may play an important role in the development of

  10. Relaxant Effect of Daurinoline on Vascular Smooth Muscle of Isolated Rabbit Basilar Artery%蝙蝠葛诺林碱对家兔体外基底动脉血管平滑肌舒张作用的研究

    Institute of Scientific and Technical Information of China (English)

    陈密; 崔海东; 郝素芳; 卢云; 郭莲军

    2014-01-01

    Objective To investigate the effect of daurinoline on basilar artery vascular smooth muscle. Methods The tension of isolated basilar artery ring of rabbit was measured. The effects of daurinoline on the basilar artery contracted by methoxamine,5-hydroxytryptamine(5-HT),KCl and Histamine( His)were also examined. Dose-response curves of 5-HT and KCl were observed as well. Results Daurinoline exerted obvious relaxation effect on the basilar artery vascular ring contracted by methoxamine,5-HT,KCl and His in a concentration-dependent manner. IC50 of daurinoline in methoxamine,5-HT,KCl and His-treated rabbits was 8.67×10-5,1.78×10-6,6.79×10-7 and 4.98×10-4 mol·L-1,respectively. The change of concentration-response curves of methoxamine,5-HT,KCl and His showed that daurinoline was a non-competitive antagonist. Conclusion Daurinoline exerts marked relaxation effect on basilar artery of rabbits through non-competitive antagonism. The mechanism of relaxation action may be related to blockage of voltage-dependent or receptor-dependent calcium channels.%目的:探讨蝙蝠葛诺林碱对家兔基底动脉血管平滑肌的舒张作用。方法制备家兔基底动脉血管环,采用半对数摩尔浓度累积给药方法,观察给予蝙蝠葛诺林碱对家兔基底动脉血管平滑肌的舒张作用。结果蝙蝠葛诺林碱对甲氧胺、5-羟色胺、氯化钾和组胺所致的家兔基底动脉收缩均有明显的扩张作用,最大舒张50%( IC50)浓度分别为8.67×10-5,1.78×10-6,6.79×10-7,4.98×10-4 mol·L-1。同时对甲氧胺、5-羟色胺、氯化钾和组胺所致量效曲线的影响,均显示为非竞争性拮抗作用。结论蝙蝠葛诺林碱通过非竞争性拮抗作用,能有效舒张家兔基底动脉血管平滑肌,改善脑循环。

  11. The Rabbit Stream Cipher

    DEFF Research Database (Denmark)

    Boesgaard, Martin; Vesterager, Mette; Zenner, Erik

    2008-01-01

    The stream cipher Rabbit was first presented at FSE 2003, and no attacks against it have been published until now. With a measured encryption/decryption speed of 3.7 clock cycles per byte on a Pentium III processor, Rabbit does also provide very high performance. This paper gives a concise...... description of the Rabbit design and some of the cryptanalytic results available....

  12. Aortic Valve Stenosis

    Science.gov (United States)

    ... evaluation of aortic stenosis in adults. http://www.uptodate.com/home. Accessed April 29, 2014. Mohty D, ... Valvular heart disease in elderly adults. http://www.uptodate.com/home. Accessed May 2, 2014. Bonow RO, ...

  13. Bicuspid aortic valve

    Science.gov (United States)

    ... aortic disease. In: Otto CM, Bonow RO, eds. Valvular Heart Disease: A Companion to Braunwald's Heart Disease . 4th ed. ... PA: Elsevier Saunders; 2014:chap 13. Carabello BA. Valvular heart disease. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  14. Aortic Valve Regurgitation

    Science.gov (United States)

    ... inside your heart that involves heart valves. Rheumatic fever. Rheumatic fever — a complication of strep throat and once a ... the United States — can damage the aortic valve. Rheumatic fever is still prevalent in developing countries but rare ...

  15. The construction of recombinant β-galactosidase adenovirus and its expression in transduced rat aortic smooth muscle cells%重组β-半乳糖苷酶腺病毒载体的构建及其在血管平滑肌细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    王家宁; 黄永章; 王俊峰; 王卫民; 李瑞明; 葛永贵; 张群林

    2000-01-01

    Objective To construct a replication-defective recombinant adenovirus expressing β-galactosidase for providing a control vector in future study of gene therapy for restenosis, and of safety, feasibility, and efficiency of gene transfer mediated by adenovirus. Methods The shuttle vector pAd-β-gal was constructed by recombinant DNA technology and characterized by endonuclease digestion and agarose gel electrophoresis. Ad-β- gal was generated by homologous recombination and characterized by staining the transfected 293 cells with X-gal. The virus titer was determined by measuring the absorbance at 260 nm. Rat aortic vascular smooth muscle cells (VSMCs) were cultured by explant methods and characterized by specific smooth muscle α- actin immunohistochemical staining. VSMCs were transfected with Ad- β- gal at 100 moi and stained with X-gal to observe the expression of β-galactosidase. Results (1)pAd-β-gal shuttle vector and Ad -β-gal were constructed successfully; (2)The transfected 293 cells and VSMCs were stained blue with X - gal; (3)The virus titer is 9×1011 pfu/ml;(4)The efficiency of gene transfer in VSMCs at 100 moi was nearly 100%. Conclusions ( 1)The recombinant adenovirus expressing β-galactosidase, Ad -β-gal, was constructed, successfully; (2) This investigation provides an excellent control vector for future study of gene therapy in restenosis;(3)Ad-β-gal is a useful tool in the research of safety, feasibility and the efficiency of gene transfer mediated by adenovirus.%目的:构建表达β-半乳糖苷酶(β-gal)的重组腺病毒,以期为再狭窄的基因治疗研究提供一个对照载 体和为腺病毒介导的基因转移的安全性、可行性、转染效率的研究提供一有用的工具。方法:采用基因重组方法构 建穿梭质粒pAd-β-gal,通过同源重组法制备出重组腺病毒Ad-β-gal,转染的293细胞用X-gal染色鉴定Ad-β -gal的正确与否。通过测定260 nm的紫外光吸收值估计病毒高度

  16. [Inflammatory abdominal aortic aneurysm].

    Science.gov (United States)

    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.

  17. Smooth Neutrosophic Topological Spaces

    Directory of Open Access Journals (Sweden)

    M. K. EL Gayyar

    2016-08-01

    Full Text Available As a new branch of philosophy, the neutrosophy was presented by Smarandache in 1980. It was presented as the study of origin, nature, and scope of neutralities; as well as their interactions with different ideational spectra. The aim in this paper is to introduce the concepts of smooth neutrosophic topological space, smooth neutrosophic cotopological space, smooth neutrosophic closure, and smooth neutrosophic interior. Furthermore, some properties of these concepts will be investigated.

  18. Smooth Neutrosophic Topological Spaces

    OpenAIRE

    M. K. EL GAYYAR

    2016-01-01

    As a new branch of philosophy, the neutrosophy was presented by Smarandache in 1980. It was presented as the study of origin, nature, and scope of neutralities; as well as their interactions with different ideational spectra. The aim in this paper is to introduce the concepts of smooth neutrosophic topological space, smooth neutrosophic cotopological space, smooth neutrosophic closure, and smooth neutrosophic interior. Furthermore, some properties of these concepts will be investigated.

  19. 右美托咪定对家兔结肠平滑肌自发收缩功能的影响:离体实验%Effect of dexmedetomidine on spontaneous contraction of colon smooth muscles of rabbits in vitro

    Institute of Scientific and Technical Information of China (English)

    申军梅; 苗穗兵; 李旭懿; 崔芳华; 李煜; 李楠; 刘宸光; 靳睿哲; 关玥

    2016-01-01

    能,机制可能与激活一氧化氮途径、抑制外钙内流和内钙释放有关.%Objective To investigate the effect of dexmedetomidine on the spontaneous contraction of colon smooth muscles of rabbits.Methods Healthy rabbits of both sexes,aged 2-3 months,weighing 1.8-2.3 kg,were sacrificed to prepare colon smooth muscle specimens which were incubated with the K-H solution.Treatment with drugs was performed after incubation was stable (baseline).Experiment Ⅰ Six colon segments were selected,and dexmedetomidine was accumulatively added to the K-H solution with the final conccntrations of 1,10,20,40,60 80 and 100 nmol/L in sequence.Experiment Ⅱ Six colon segments were selected,dexmedetomidine was added to the K-H solution (final concentration 60 nmol/L),and the colon segments were incubated for 3 min followed by washout,NG-nitro-L-arginine methyl ester (final concentration 100 mmol/L) was then added to the K-H solution,the colon segments were then incubated for 10 min,and then dexmedetomidine (final concentration 60 nmol/L) was added again.Experiment Ⅲ Twelve colon segments were randomly divided into 2 groups (n =6 each) using a random number table:CaCl2 group and dexmedetomidine+ CaCl2 group.The culture medium was replaced with calciumfree K-H solution,and 5 min later CaCl2 (final concentration 1.8 mol/L) was added in CaCl2 group.The culture medium was replaced with calcium-free K-H solution,the colon segments were incubated for 5 min,dexmedetomidine (final concentration 60 nmol/L) was added,the colon segments were then incubated for 10 min,and then CaCl2 (final concentration 1.8 mol/L) was added in dexmedetomidine+ CaCl2 group.Experiment Ⅳ Twelve colon segments were randomly divided into 2 groups (n=6 each) using a random number table:ryanodine group and dexmedetomidine+ryanodine group.The culture medium was replaced with calcium-free K-H solution,the colon segments were incubated for 5 min,and then ryanodine (final concentration 0.2 mmol/L) was added

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

    Science.gov (United States)

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

    2013-08-08

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

  1. Variant rabbit hemorrhagic disease virus in young rabbits, Spain.

    Science.gov (United States)

    Dalton, Kevin P; Nicieza, Inés; Balseiro, Ana; Muguerza, María A; Rosell, Joan M; Casais, Rosa; Álvarez, Ángel L; Parra, Francisco

    2012-12-01

    Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.

  2. Smooth K-Theory

    CERN Document Server

    Bunke, Ulrich

    2007-01-01

    We construct an analytic multiplicative model of smooth K-theory. We further introduce the notion of a smooth K-orientation of a proper submersion and define the associated push-forward which satisfies functoriality, compatibility with pull-back diagrams, and projection and bordism formulas. We construct a multiplicative lift of the Chern character from smooth K-theory to smooth rational cohomology and verify that the cohomological version of the Atiyah-Singer index theorem for families lifts to smooth cohomology.

  3. Effects of Four Interior-warming Drugs on the Tension of Ileum Smooth Muscle and Ca2+-ATPase in Rabbits%4种温里药对兔回肠平滑肌张力及Ca2+-ATP 酶的影响

    Institute of Scientific and Technical Information of China (English)

    黄庆芳; 陈艳芬; 杨全; 杨超燕; 唐春萍; 明露; 黎洁玲; 陶曙红

    2016-01-01

    Objective To investigate the effects of four interior-warming drugs( galangal,cinnamon,evodia rutaecarpa,and dried ginger)on the tension of ileum smooth muscle and Ca2+-ATPase on the cell membrane in rabbits. Methods The effects of galangal,cinnamon,evodia rutaecarpa,and dried ginger were examined on normal ileum smooth muscle,in vitro intestinal muscle contraction caused by acetylcholine(ACh),barium chloride(BaCl2 )and histamine(His), and ACh-induced calcium release by using BL-420E+ biological signal collection and processing system.The average tension was measured within 1 min before delivery and within 3 minutes after the treatment,and the inhibition rate was calculated according to the average tension value.The effects of sera containing galangal,cinnamon,evodia rutaecarpa,and dried ginger on Ca2+-ATPase activity on the cell membrane of the intestinal smooth muscle were examined by phosphorus method. Results Galangal,cinnamon,evodia rutaecarpa,and dried ginger at high concentrations could restrain in vitro intestinal contraction in normal circumstances(P<0.05 or P<0.01).Significant inhibitory effects on intestinal contraction caused by ACh,His and BaCl2 were found in low,medium and high concentration groups(P<0.01).There was a dose-effectiveness relationship between the inhibition rate and final drug concentrations.The ACh-induced intracellular and extracellular calcium dependent contraction were significantly inhibited by the four interior-warming drugs( P < 0. 05 or P < 0. 01). The Ca2+-ATPase activities were( 0. 384 ± 0.070),(0.302±0.016),(0.307±0.016),(0.296±0.016),(0.313±0.003)U·mg-1 ,respectively,in intestinal smooth muscle in normal control group and high concentration groups of galangal,cinnamon,evodia rutaecarpa,and dried ginger(P<0.01). Conclusion Interior-warming drugs may relax intestinal smooth muscle by reducing the intracellular calcium release and the extracellular calcium inflow via receptor-controlled calcium channels,and inhibiting the

  4. Screening for Abdominal Aortic Aneurysm

    Science.gov (United States)

    Understanding Task Force Recommendations Screening for Abdominal Aortic Aneurysm The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Abdominal Aortic Aneurysm. This final ...

  5. Abdominal aortic aneurysm repair - open

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007392.htm Abdominal aortic aneurysm repair - open To use the sharing features on this page, please enable JavaScript. Open abdominal aortic aneurysm repair is surgery to fix a widened part ...

  6. [Congenital aortic stenosis].

    Science.gov (United States)

    Yamaguchi, M

    2001-08-01

    Recent advances in and controversies concerning the management of children with congenital valvular aortic stenosis are discussed. In neonates with critical aortic stenosis, improved survival has recently been reported after surgical open valvotomy and balloon valvuloplasty, although it is difficult at this point to compare the results of the two procedures and determine their differential indications. Good results have also been achieved after extended aortic valvuloplasty for recurrent aortic stenosis and/or insufficiency, but the length of follow-up in these patients is still short. The technique first reported in 1991 for bilateral enlargement fo a small annulus permits the insertion of an aortic valve 3-4 sizes larger than the native annulus. It entails no risk of distorting the mitral valve, damaging the conduction system or important branches of the coronary arteries, or resulting in left ventricular dysfunction. The Ross procedure is now widely applied in the West, with reports of early mortality rates of less than 5% and event-free survival rates of 80-90% during follow-up of 4-8 years. Longer follow-up and continued careful evaluation are required to resolve the issue of possible dilatation and subsequent neoaortic valve dysfunction and pulmonary stenosis due to allograft degeneration after pulmonary autograft root replacement in children.

  7. Toxicology and pharmacology of some euthenium compounds: vascular smooth muscle relaxation by nitrosyl derivatives of ruthenium and iridium

    Energy Technology Data Exchange (ETDEWEB)

    Kruszyna, H.; Kruszyna, R.; Hurst, J.; Smith, R.P.

    1980-07-01

    A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55; dichlorobis(2,2'-dipyridyl)ruthenium(II) 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occuring in 4 to 7 d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be due to the metal and not to its associated ligands. Only complexes having a nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic argonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominum when these isolated muscles had been contracted by acetylcholine. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimllylethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.

  8. [Effect of adrenaline on the proliferation of the tunica media smooth muscle cells of rat aorta in culture].

    Science.gov (United States)

    Blaes, N; Bourdillon, M C; Crouzet, B; Suplisson, A; Boissel, J P

    1980-03-24

    The proliferation of Rat medial aortic smooth muscle cells in secondary cultures is increased with adrenalin. The maximal effect is obtained after 3 days and the increase is dose-dependent. Thus adrenalin might be one of the factors responsible for the proliferation of smooth muscle cells that could play a key role in the formation of the atherosclerotic plaque in vivo.

  9. Insights into acute aortic dissection

    NARCIS (Netherlands)

    Trimarchi, S.

    2012-01-01

    Aortic dissection represents one of the most catastrophic and complex cardiovascular diseases. Its origin is related to an intimal tear with course of blood flow into the aortic wall and division of the aortic lumen into two different lumens, defined as the true and false lumen, separated by a

  10. Allergic Lung Inflammation Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice

    DEFF Research Database (Denmark)

    Liu, Cong-Lin; Wang, Yi; Liao, Mengyang

    2016-01-01

    OBJECTIVE: Asthma and abdominal aortic aneurysms (AAA) both involve inflammation. Patients with asthma have an increased risk of developing AAA or experiencing aortic rupture. This study tests the development of one disease on the progression of the other. APPROACH AND RESULTS: Ovalbumin...... sensitization and challenge in mice led to the development of allergic lung inflammation (ALI). Subcutaneous infusion of angiotensin II into mice produced AAA. Simultaneous production of ALI in AAA mice doubled abdominal aortic diameter and increased macrophage and mast cell content, arterial media smooth...

  11. 旋覆代赭汤对反流性食管炎家兔食管下括约肌L型钙通道的作用研究%Regulation of L-type Calcium Channels by Xuanfu Daizhe Soup in the Lower Esophageal Sphincter Smooth Muscle of Rabbit Reflux Esophagitis Model

    Institute of Scientific and Technical Information of China (English)

    张俊杰; 吴茂申

    2014-01-01

    Objective]To research the regulation of L-type calcium channels by Xuanfu Daizhe soup in the lower esophageal sphincter(LES) smooth muscle of rabbit reflux esophagitis model induced by mixed perfusion of hydrochloric acid and bile. [Methods]Established the rabbit model of mixed reflux esophagitis, nifedipine was used to block L-type calcium channel.The muscle tension of L-type calcium channel were compared among groups in the experiments. [Results]The calcium releasing and flowing phase of LES in the model group was higher than that in the normal group, the whole recipe group, sweet-scending group, the getting rid of bitter-reducing group and the getting rid of lifting and declining group( P0.05). There was no significant difference between the normal group and the whole recipe group in calcium releasing and flowing phase of LES( P>0.05). [Conclusion]The decreasing of reflux esophagitis model LES tension was relevant with the L-type calcium channel dysfunction;Xuanfu Daizhe soup could improve the LES tension by regulating L-type calcium channels. The sweet-ascending group had a remarkable effect among those dismantle prescription groups.%[目的]研究旋覆代赭汤对酸和胆汁混合致反流性食管炎家兔食管下括约肌(LES)L型钙通道的调控机制。[方法]制备家兔反流性食管炎模型,用硝苯地平(nifedipine)阻断L型钙通道,比较各组LES环行肌L型钙通道阻断前后张力幅度的差异。[结果]L型钙通道阻断前后各组LES环行肌张力比较:正常组、全方组、甘升组、去苦降组、去升降相因组LES环行肌钙释放相、内流相张力均高于模型组(P<0.01),而苦降组、升降相因组、去甘升组LES环行肌钙释放相与模型组相比无显著性差异(P>0.05),正常组与全方组LES环行肌钙释放相、内流相张力相比无显著性差异(P>0.05)。[结论]酸和胆汁混合致反流性食管炎模型家兔LES环行肌张力下降,与L型钙通道功能障碍

  12. Robotic aortic surgery.

    Science.gov (United States)

    Duran, Cassidy; Kashef, Elika; El-Sayed, Hosam F; Bismuth, Jean

    2011-01-01

    Surgical robotics was first utilized to facilitate neurosurgical biopsies in 1985, and it has since found application in orthopedics, urology, gynecology, and cardiothoracic, general, and vascular surgery. Surgical assistance systems provide intelligent, versatile tools that augment the physician's ability to treat patients by eliminating hand tremor and enabling dexterous operation inside the patient's body. Surgical robotics systems have enabled surgeons to treat otherwise untreatable conditions while also reducing morbidity and error rates, shortening operative times, reducing radiation exposure, and improving overall workflow. These capabilities have begun to be realized in two important realms of aortic vascular surgery, namely, flexible robotics for exclusion of complex aortic aneurysms using branched endografts, and robot-assisted laparoscopic aortic surgery for occlusive and aneurysmal disease.

  13. 油菜籽粕生物碱对家兔离体肠平滑肌收缩功能的影响及机制%Effect of rapeseed meal al kaloid on the contractility of isolated ileum smooth muscle of rabbits

    Institute of Scientific and Technical Information of China (English)

    刘世超; 秦海宏; 卢轩; 冯宝民; 郑学仿; 王惠国

    2014-01-01

    Abtsract:Objective To observe the effect of rapeseed meal alkaloid on the contractility of isolated ileum smooth muscle of rabbits .Methods Fifteen fasted twenty four hours rabits executed by knock on the head , slited abdomen quickly and separated isolated ileum smooth muscle , the top of isolated ileum smooth muscle connected with tonotransducer and the bottom fasten on the metal hook , adjust the load at2.0 g, steady peristalsis in 30 min.To filtrate thirteen steady frequency and tension ileum in thirteen bath , add rapeseed meal alkaloid 0、0.5、1、2、4、6、8、10、20、40、60、80、100μg/μL with them separately ,each dose volume is 5μL, 0μg/μL rapeseed meal alkaloid as the blank control , recorded and analyzed peristal-tic waves with Medlab -U/4C501H biological function experimental system , measured after treated frequency by cycle measurement and after treated tension by interval measurement .The muscle strips were incubated with M receptor blocker (atropine)to observe the effects of rapeseed meal alkaloid contractile activity in the presence of atropine .Results 0、0.5、1、2、4、6、8、10、20、40、60、80、100 μg/μL rapeseed meal alkaloid had no obvious effect on the contraction frequency of isola -ted ileum smooth muscle strips .The 6-60μg/μL of rapeseed meal alkaloid compared with the blank control can obviously increase the tension of muscle strips(P<0.05), the contractile activity increased with the dose (from 0.5 μg/μL to 40μg/μL).M receptor blocker(atropine) can inhibit the contraction effect caused by rapeseed meal alkaloid but the effect is incomplete .Conclusions Rapeseed meal alkaloi has excitatory effect on the contraction effect of isolated ileum smooth mus -cle and the effect was related with the M receptor excitement .%目的:观察油菜籽粕生物碱对家兔离体肠平滑肌收缩功能的影响。方法取禁食24 h家兔15只,槌击后枕部致死,迅速剖开腹腔,制备离体肠管,肠管上

  14. Aortic valve replacement

    DEFF Research Database (Denmark)

    Kapetanakis, Emmanouil I; Athanasiou, Thanos; Mestres, Carlos A

    2008-01-01

    BACKGROUND AND AIMS OF THE STUDY: Prompted by anecdotal evidence and observations by surgeons, an investigation was undertaken into the potential differences in implanted aortic valve prosthesis sizes, during aortic valve replacement (AVR) procedures, between northern and southern European...... countries. METHODS: A multi-institutional, non-randomized, retrospective analysis was conducted among 2,932 patients who underwent AVR surgery at seven tertiary cardiac surgery centers throughout Europe. Demographic and perioperative variables including valve size and type, body surface area (BSA) and early...

  15. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged...... with dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...... and at termination, also in lipoproteins. Aortic atherosclerosis was evaluated as cholesterol content and area covered by plaque. Plasma cholesterol was not significantly different between the groups at termination (35.7 mmol/L vs. 35.5 mmol/L). A significant increase in LDL was seen (13.1 mmol/L vs. 16.5 mmol...

  16. THE EFFECT OF CORTISONE ON THE SERUM LIPIDS AND ON THE DEVELOPMENT OF EXPERIMENTAL CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT

    Science.gov (United States)

    Gordon, Dina; Kobernick, Sidney D.; McMillan, Gardner C.; Duff, G. Lyman

    1954-01-01

    An experiment was performed to determine the effect of cortisone on the serum lipids and on the development of experimental cholesterol atherosclerosis in the rabbit. Litter mate rabbits of the same sex were employed; both sexes were represented in the experiment. The report is based upon four experimental groups comprising (1) 12 rabbits fed cholesterol and treated with cortisone vehicle; (2) 12 rabbits fed cholesterol and treated daily with cortisone; (3) 11 rabbits treated with cortisone; and (4) 7 rabbits that received cortisone vehicle. It was observed that: (1) There was less aortic atherosclerosis in the cholesterol-fed cortisone-treated rabbits as judged by both morphological and chemical means than in the rabbits fed cholesterol without cortisone treatment. (2) Cortisone depressed appreciably the hypercholesterolemia resulting from the feeding of cholesterol to rabbits. (3) Cortisone treatment caused a moderate hypercholesterolemia in normal rabbits. (4) Cortisone caused a moderate increase in serum lipid phosphorus equal to that produced by cholesterol feeding alone. (5) The combination of cholesterol feeding and cortisone did not result in a higher phospholipidemia than either one of these agents alone. (6) Cortisone caused a great increase in serum-neutral fat; it was not apparent whether cholesterol feeding affected the neutral fat lipemia due to cortisone treatment alone. (7) The total cholesterol to lipid phosphorus ratio was about normal in the rabbits that received cortisone only. It was doubled in the animals receiving both cholesterol and cortisone, and it was increased about four times in those that received only cholesterol. The significance of the alterations in the serum lipids induced by cortisone is discussed in relation to the inhibition of the development of aortic atherosclerosis that occurred in the cholesterol-fed rabbits treated with cortisone. PMID:13152282

  17. Unoperated aortic aneurysm

    DEFF Research Database (Denmark)

    Perko, M J; Nørgaard, M; Herzog, T M;

    1995-01-01

    From 1984 to 1993, 1,053 patients were admitted with aortic aneurysm (AA) and 170 (15%) were not operated on. The most frequent reason for nonoperative management was presumed technical inoperability. Survivals for patients with thoracic, thoracoabdominal, and abdominal AA were comparable...... hypertension were predictive of mortality, whereas...

  18. 有氧运动对大鼠心血管和胸主动脉平滑肌的功能重塑作用%Functional Remodeling of the Aerobic Exercise on the Cardiovascular System and Thoracic Aortic Smooth Muscle of Rats

    Institute of Scientific and Technical Information of China (English)

    石丽君; 李珊珊; 熊开宇; 龚丽景

    2011-01-01

    Objective: To investigate the aerobic exercise-induced functional remodeling of the rat cardiovascular systmem and thoracic aortic smooth muscle,and to explore the possible potassium channel mechanisms underlying these effects.Methods: 20 male Wistar rats(2M) were randomly divided into sedentary group and exercise group.Training protocol: 8 week treadmill.After 8 weeks,some animals(n=5 in each group) underwent femoral arterial and venous cannulation.Catheters were tunneled subcutaneously,exteriorized at the nape of the neck.Following one day recovery,the basal blood pressure,heart rate and the cardiovascular responses to intravenous(i.v.) injection of Ang II and non-specific K+ channel blocker TEA were monitored in vivo.In the other 10 animals,the thoracic aorta was carefully exposed after thoracotomy and dissected free.Segments were cut into rings and the endothelial cell lining was removed.The vessel contractility was examined in vitro.Results:1) After the aerobic exercises,the heart rate at rest reduced significantly.The mean arterial pressure of rats had a tendency to decrease but there was no significant difference between the sedentary and the exercise groups at rest.2)The pressor responses induced by i.v.injection of Ang II were attenuated in the exercise group compared with that in the sedentary group;3) The pressor responses induced by i.v.injection of TEA,was significantly enhanced after exercise training;4)Ang II(10-9~10-4M) caused a significantly increase of vascular tone in a concentration-dependent manner in both groups,while the increase amplitude was less in exercise group than in the sedentary group;5) TEA(5×10-3 M) could induce an increase of vessel contractility in two groups,while the amplitude of increase was significantly enhanced after exercise training.Conclusion: Aerobic exercise training can induce functional remodeling of the rat cardiovascular system and thoracic aorta smooth muscle,in which

  19. 模拟失重大鼠胸主动脉平滑肌细胞凋亡的变化及间断性人工重力对抗的影响%Effects of 3-week simulated microgravity and intermittent artificial gravity on apoptosis of thoracic aortic smooth muscle cells in rats

    Institute of Scientific and Technical Information of China (English)

    蔡越; 於进文; 白云刚; 刘焕; 王忠超; 暴军香; 马进

    2012-01-01

    [目的]:观察模拟失重大鼠胸主动脉平滑肌细胞凋亡的变化及间断性人工重力对其影响.[方法]:将27只SD大鼠随机分为3组(每组9只),即对照组(CON)、模拟失重组(SUS)及站立对抗组(STD).以尾部悬吊大鼠模拟失重3周,同期每天悬吊23h、站立1h模拟间断性人工重力对抗的效果.用TUNEL染色法检测SUS组、同步对照(CON)组及STD组大鼠胸主动脉平滑肌细胞的凋亡情况;用Western blot法检测各组大鼠胸主动脉组织中Bad、FasL及Caspase-3蛋白表达的变化.[结果]:与CON组比较,SUS组大鼠胸主动脉平滑肌细胞TUNEL染色阳性的细胞明显减少(P<0.01);STD组TUNEL染色阳性的细胞较CON组及SUS组显著增加(P<0.01).SUS组Bad的表达较CON组和STD组显著减少(P<0.05),STD组Bad的表达较CON组有增加的趋势,但无统计学差异.SUS组FasL及Caspase-3的表达较CON组显著降低(P<0.05);STD组FasL及Caspase-3的表达较CON组及SUS组显著增高(P<0.01).[结论]:模拟失重可减少大鼠胸主动脉平滑肌细胞凋亡,每日1h的-Gx对抗可使胸主动脉平滑肌细胞的凋亡增加,提示血管组织平滑肌细胞的凋亡在失重引起的动脉血管适应性重构中可能发挥重要作用.%AIM: To investigate the effects of 3-week simulated microgravity and intermittent artificial gravity on apoptosis of thoracic aortic smooth muscle cells (TASMCs) in rats. METHODS: Twenty seven Sprague Dawley rats were randomly divided into three groups with nine rats in each group: control group (CON) , tail-suspended group (SUS) and standing group (STD). SUS rats were used to simulate the effects of microgravity and homochronous countermeasure (STD, daily 1 h of -Gx gravitation) was used to simulate the effects of intermittent artificial gravity (IAG). Apoptosis of TASMCs was assessed by TUNEL staining, and protein expressions of Bad, FasL and Caspase-3 in thoracic aorta tissues were observed by Western blot. RESULTS

  20. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

    Science.gov (United States)

    Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

    2015-02-01

    Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.

  1. Autoantibody Production in Rabbits

    Science.gov (United States)

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  2. Post-stenotic aortic dilatation

    Directory of Open Access Journals (Sweden)

    Jahangiri Marjan

    2006-03-01

    Full Text Available Abstract Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation.

  3. Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

    Institute of Scientific and Technical Information of China (English)

    ZHAO Quan-ming; FENG Ting-ting; ZHAO Xin; XU Zhan-min; LIU Yu; LI De-peng; LI Li-qin; SU Gong; ZHANG Xiao-xia

    2011-01-01

    Background Atherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture (vulnerable plaque) could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit model.Methods Ten male New Zealand White rabbits were divided into three groups as follows: (1) normal control group (n=2,C group): the animals were fed a standard diet at 120 g/d and were given water ad labium; (2) atherosclerosis group (n=4,As group): animals were fed with high fat diet for 5 months after aortic endothelia damage; (3) treatment group (atherosclerosis + atorvastatin, n=4, Statin group): animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin (2.5 mg·d-1·kg-1) treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodexyglucose positron emission tomography/computed tomography (PET/CT) and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio (TBR). Maximal standardized uptake value (SUV) was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell (SMC) number, CD-14 antibody positive cell (macrophage) number and the ratio of the thickness of fibrous cap to the thickness of lipid core (cap-to-core ratio) in atherosclerotic plaques were analyzed.Results As group showed significantly higher uptake of FDG than C group (SUVs: 0.746±0.172 vs. 0.286±0.073, P <0.001). After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly (Statin group:0.550±0.134, compared to As group

  4. Tobacco smoking and aortic aneurysm

    DEFF Research Database (Denmark)

    Sode, Birgitte F; Nordestgaard, Børge G; Grønbæk, Morten

    2012-01-01

    BACKGROUND: We determined the predictive power of tobacco smoking on aortic aneurysm as opposed to other risk factors in the general population. METHODS: We recorded tobacco smoking and other risk factors at baseline, and assessed hospitalization and death from aortic aneurysm in 15,072 individuals...... General Population Study, respectively. According to the magnitude of the hazard ratios, tobacco consumption was the most important risk factor for hospitalization and death from aortic aneurysm, followed by male sex and hypertension in both cohorts. The population attributable risk of aortic aneurysm...... outcomes due to tobacco consumption was 64% and 47% in the Copenhagen City Heart Study and Copenhagen General Population Study, respectively, and ranked highest among population attributable risks of aortic aneurysm in both cohorts. The absolute 10-year risk for hospitalization or death from aortic...

  5. Characterization of human aortic elastase found in patients with abdominal aortic aneurysms.

    Science.gov (United States)

    Cohen, J R; Mandell, C; Wise, L

    1987-10-01

    Recent evidence indicates that the homeostatic balance between elastase and antiprotease activity is altered in the infrarenal aorta of those patients with different types of aortic pathologic findings. The specific properties of elastase found in the aorta of patients with abdominal aortic aneurysms (AAA) are discussed herein. Activity of elastase extracted from ten pooled AAA specimens was observed when incubated with several inhibitors: 13.2 per cent for phenyl-suphonyl flouride (PSF); 43.3 per cent for ethylenediaminetetraacetic acid (EDTA); 77.7 per cent for pepstatin; 137.0 per cent for leupeptin, and 24.0 per cent for alpha-1-antitrypsin. Irreversible inhibition by PSF indicates that the elastase is a serine protease. The elastase is most likely not a metallo enzyme, since it had no absolute requirement for divalent cations as indicated by only partial inhibition by EDTA. Elastase activity is most likely not due to cathepsins B or D, since cathepsins are active in an acid pH and selectively inhibited by leupeptin and pepstatin. The pH curve revealed a maximum activity at pH 8.2 and elastase activity was significantly inhibited by alpha-1-antitrypsin in a dose response manner determining functional elastase activity. These data indicate that the elastase in the aorta of patients with an AAA has the exact properties of the serine elastase found in the smooth muscle cells of the aorta in rats. These results also confirm the critical role of alpha-1-antitrypsin in determining functional elastase activity. Smooth muscle cell regulation of elastin metabolism may be important in determining why some patients have AAA and others have occlusive aortic disease develop.

  6. Smooth sandwich gravitational waves

    CERN Document Server

    Podolsky, J

    1999-01-01

    Gravitational waves which are smooth and contain two asymptotically flat regions are constructed from the homogeneous pp-waves vacuum solution. Motion of free test particles is calculated explicitly and the limit to an impulsive wave is also considered.

  7. smooth-muscle activity

    African Journals Online (AJOL)

    with atropine could not abolish the effect of the venom on smooth muscle. ... cholenergic factor with acetylcholine was confirmed using radioimmunoassay of ... peripheral nervous antagonists on the venom action are still uncertain. The present.

  8. Zoonoses of rabbits and rodents.

    Science.gov (United States)

    Hill, William Allen; Brown, Julie Paige

    2011-09-01

    Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

  9. Ruptured abdominal aortic aneurysm.

    Science.gov (United States)

    Sachs, T; Schermerhorn, M

    2010-06-01

    Ruptured abdominal aortic aneurysm (AAA) continues to be one of the most lethal vascular pathologies we encounter. Its management demands prompt and efficient evaluation and repair. Open repair has traditionally been the mainstay of treatment. However, the introduction of endovascular techniques has altered the treatment algorithm for ruptured AAA in most major medical centers. We present recent literature and techniques for ruptured AAA and its surgical management.

  10. Infrarenal Aortic Occlusion

    Science.gov (United States)

    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. Rabbit orthopedic surgery.

    Science.gov (United States)

    Rich, Gregory A

    2002-01-01

    Orthopedic surgery in rabbits poses several unique parameters for the veterinary surgeon. It is imperative for the veterinarian to be knowledgeable about the anatomic features of the surgical repair site and to become familiar with a rabbit's pain and discomfort often associated with orthopedic injuries. Handling the perioperative and postoperative pain and potential GI disturbances are crucial for a successful outcome of the surgical case. This article is designed to help the veterinary surgeon prepare for the orthopedic surgical procedure and the peripheral physiologic needs of the rabbit from presentation through recovery.

  12. RabbitMQ essentials

    CERN Document Server

    Dossot, David

    2014-01-01

    This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

  13. CT of thoracic aortic aneurysms.

    Science.gov (United States)

    Posniak, H V; Olson, M C; Demos, T C; Benjoya, R A; Marsan, R E

    1990-09-01

    Aneurysms of the thoracic aorta are most often the result of arteriosclerotic disease. Other causes include degeneration of the medial layer of the aortic wall, either idiopathically or due to genetic disorders such as Marfan syndrome; aortic dissection; trauma; syphilis and other bacterial infection; noninfective aortitis; and congenital anomaly. We review normal anatomy of the aorta and discuss our technique and interpretation of computed tomography (CT) in the evaluation of the thoracic aorta. We illustrate the CT appearance of different types of aortic aneurysms as well as discuss the use of CT for assessing complications of aneurysms, for postoperative follow-up, and in the differentiation of aortic aneurysm from a paraaortic mass.

  14. Micromanaging Abdominal Aortic Aneurysms

    Directory of Open Access Journals (Sweden)

    Lars Maegdefessel

    2013-07-01

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

  15. siRNA-mediated knockdown of endogenously expressed bestrophin in smooth muscles

    DEFF Research Database (Denmark)

    Larsen, Per; Matchkov, Vladimir; Nilsson, Holger

    was used. Cultured aortic smooth muscle cells (A7r5) were transfected with siRNA directed against bestrophin-4 and cultured for 3 days. The efficiency of transfection was demonstrated by specific perinuclear fluorescence of Cy3-labelled siRNA. The downregulation of targeted protein expression...

  16. Smoothing error pitfalls

    Science.gov (United States)

    von Clarmann, T.

    2014-09-01

    The difference due to the content of a priori information between a constrained retrieval and the true atmospheric state is usually represented by a diagnostic quantity called smoothing error. In this paper it is shown that, regardless of the usefulness of the smoothing error as a diagnostic tool in its own right, the concept of the smoothing error as a component of the retrieval error budget is questionable because it is not compliant with Gaussian error propagation. The reason for this is that the smoothing error does not represent the expected deviation of the retrieval from the true state but the expected deviation of the retrieval from the atmospheric state sampled on an arbitrary grid, which is itself a smoothed representation of the true state; in other words, to characterize the full loss of information with respect to the true atmosphere, the effect of the representation of the atmospheric state on a finite grid also needs to be considered. The idea of a sufficiently fine sampling of this reference atmospheric state is problematic because atmospheric variability occurs on all scales, implying that there is no limit beyond which the sampling is fine enough. Even the idealization of infinitesimally fine sampling of the reference state does not help, because the smoothing error is applied to quantities which are only defined in a statistical sense, which implies that a finite volume of sufficient spatial extent is needed to meaningfully discuss temperature or concentration. Smoothing differences, however, which play a role when measurements are compared, are still a useful quantity if the covariance matrix involved has been evaluated on the comparison grid rather than resulting from interpolation and if the averaging kernel matrices have been evaluated on a grid fine enough to capture all atmospheric variations that the instruments are sensitive to. This is, under the assumptions stated, because the undefined component of the smoothing error, which is the

  17. Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Disease

    DEFF Research Database (Denmark)

    Mylotte, Darren; Lefevre, Thierry; Søndergaard, Lars

    2014-01-01

    BACKGROUND: Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). OBJECTIVES: This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. METHODS...

  18. Giant Aortic Pseudoaneurysm with Stanford Type A Aortic Dissection after Aortic Valve Replacement

    Directory of Open Access Journals (Sweden)

    Mertay Boran

    2012-01-01

    Full Text Available Giant pseudoaneurysm of the ascending aorta is a rare but dreadful complication occurring several months or years after aortic surgery. Thoracic aortic aneurysms tend to be asymptomatic and were previously often diagnosed only after a complication such as dissection or rupture. We present a rare case of giant ascending aneurysm with Stanford type A aortic dissection occurring 6 years after aortic valve replacement and also illustrate the potential dimensions the ascending aorta may reach by a pseudoaneurysm and dissection after AVR.

  19. Aortic root geometry in aortic stenosis patients (a SEAS substudy)

    DEFF Research Database (Denmark)

    Bahlmann, Edda; Nienaber, Christoph A; Cramariuc, Dana

    2011-01-01

    AIMS: To report aortic root geometry by echocardiography in a large population of healthy, asymptomatic aortic stenosis (AS) patients in relation to current vendor-specified requirements for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Baseline data in 1481 patients...... with asymptomatic AS (mean age 67 years, 39% women) in the Simvastatin Ezetimibe in AS study were used. The inner aortic diameter was measured at four levels: annulus, sinus of Valsalva, sinotubular junction and supracoronary, and sinus height as the annulo-junctional distance. Analyses were based on vendor......-specified requirements for the aortic root geometry for current available prostheses, CoreValve and Edwards-Sapien. The ratio of sinus of Valsalva height to sinus width was 1:2. In multivariate linear regression analysis, larger sinus of Valsalva height was associated with older age, larger sinus of Valsalva diameter...

  20. Attenuation of oxidative stress, inflammation, and endothelial dysfunction in hypercholesterolemic rabbits by allicin.

    Science.gov (United States)

    El-Sheakh, Ahmed R; Ghoneim, Hamdy A; Suddek, Ghada M; Ammar, El Sayed M

    2015-08-14

    Allicin, the active substance of garlic, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The present study was designed to investigate the possible beneficial effects of allicin against oxidative stress, inflammation, and endothelial dysfunction in hypercholesterolemic rabbits. Male New Zealand white rabbits were used in this study. Rabbits randomly received 1 of the following treatments: normal chow diet for 4 weeks, 1% high cholesterol diet (HCD), HCD plus allicin (10 mg/kg/day), or HCD plus atorvastatin (10 mg/kg/day). Blood samples were collected at the end of experimental diets for measurement of serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of vascular reactivity, histopathological changes, intima/media (I/M) ratio, and immunohistochemical staining of both tumor necrosis-alpha (TNF-α) and nuclear factor (NF)-κB. HCD induced significant increases in serum TC, TGs, low-density lipoprotein cholesterol (LDL-C), CRP, and MDA. Moreover, HCD caused significant decrease in serum GSH and SOD. In addition, aortic relaxation response to acetylcholine (ACh) was impaired. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both TNF-α and the oxidant-induced transcription factor, NF-κB. Allicin supplementation significantly decreased serum MDA and CRP, increased serum HDL-C, GSH, and SOD levels while nonsignificantly affecting HCD-induced elevations in serum TC and LDL-C. Additionally, allicin significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to ACh and elevation in I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, allicin has substantially

  1. FUNCTIONAL AORTIC STIFFNESS:ROLE OF CD4+ T LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    Beenish A. Majeed

    2015-08-01

    Full Text Available The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1-/- mice and additionally characterized the component of vascular stiffness due to vasoconstriction versus vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young’s modulus in C57BL/6J mice by 3-fold but caused no change in the RAG 1-/- mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1-/- mice. In order to account for the hydraulic versus material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity decreased from 3- to 2-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  2. Mitochondrial-dependent apoptosis in experimental rodent abdominal aortic aneurysms.

    Science.gov (United States)

    Sinha, Indranil; Sinha-Hikim, Amiya P; Hannawa, Kevin K; Henke, Peter K; Eagleton, Matthew J; Stanley, James C; Upchurch, Gilbert R

    2005-10-01

    While extrinsic mechanisms of apoptosis in abdominal aortic aneurysms (AAAs) are recognized, this project hypothesizes that an intrinsic, mitochondrial-dependent, mechanism of apoptosis also contributes to experimental AAA formation. Rat aortas were perfused with either saline or elastase (N = 5 per group) and harvested 7 days postperfusion. The aortas were placed in gluteraldehyde for subsequent transmission electron microscopy, Bouin's solution for TUNEL, or paraformaldehyde for immunohistochemical staining for caspase-9, caspase-3, and Bid. Abdominal aortic diameters increased 168 +/- 25% (mean +/- SEM) after elastase perfusion. compared with 30 +/- 5% after saline perfusion (P < .001). Apoptosis of aortic smooth muscle cells, macrophages, and neutrophils was evidenced by transmission electron microscopy and TUNEL in the elastase-perfused aneurysmal aortas. Quantitative analysis of the apoptotic cells revealed a significant (P < .01) increase in the number of total apoptotic cells in the elastase-perfused aortas (12 +/- 3 cells per high-power field), compared with that of saline-infused controls (1.3 +/- 0.2). Caspase-9, the key initiator in the mitochondrial-dependent apoptotic pathway, stained positively in only elastase-perfused aortas. Bid staining was not detected in either the elastase-perfused aortas or the saline controls. Apoptosis is evident in multiple cell lines in elastase-perfused aneurysmal aortas, but rarely observed in control aortas. Caspase-9, the key initiator of intrinsic apoptosis, was documented only in elastase-perfused aortas. These results suggest that mitochondrial-dependent apoptosis is associated with abdominal aortic aneurysm formation.

  3. Viral diseases of the rabbit.

    Science.gov (United States)

    Krogstad, Aric P; Simpson, Janet E; Korte, Scott W

    2005-01-01

    Viral disease in the rabbit is encountered infrequently by the clinical practitioner; however, several viral diseases were reported to occur in this species. Viral diseases that are described in the rabbit primarily may affect the integument, gastrointestinal tract or, central nervous system or maybe multi-systemic in nature. Rabbit viral diseases range from oral papillomatosis, with benign clinical signs, to rabbit hemorrhagic disease and myxomatosis, which may result in significant clinical disease and mortality. The wild rabbit may serve as a reservoir for disease transmission for many of these viral agents. In general, treatment of viral disease in the rabbit is supportive in nature.

  4. Abdominal aortic aneurysm surgery

    DEFF Research Database (Denmark)

    Gefke, K; Schroeder, T V; Thisted, B

    1994-01-01

    The goal of this study was to identify patients who need longer care in the ICU (more than 48 hours) following abdominal aortic aneurysm (AAA) surgery and to evaluate the influence of perioperative complications on short- and long-term survival and quality of life. AAA surgery was performed in 553......, 78% stated that their quality of life had improved or was unchanged after surgery and had resumed working. These data justify a therapeutically aggressive approach, including ICU therapy following AAA surgery, despite failure of one or more organ systems....

  5. Acquired smooth muscle hamartoma

    Directory of Open Access Journals (Sweden)

    Bari Arfan ul

    2006-01-01

    Full Text Available Smooth muscle hamartoma is an uncommon, usually congenital, cutaneous hyperplasia of the arrectores pilorum muscles. When it is acquired, it may be confused with Becker′s nevus. We report a case of this rare tumor in a 19-year-old man. The disease started several years ago as multiple small skin-colored papules that subsequently coalesced to form a large soft plaque on the back of the left shoulder. The diagnosis of acquired smooth muscle hamartoma was confirmed on histopathology. The patient was reassured about the benign nature of the lesion and was not advised any treatment.

  6. Revealed smooth nontransitive preferences

    DEFF Research Database (Denmark)

    Keiding, Hans; Tvede, Mich

    2013-01-01

    consumption bundle, all strictly preferred bundles are more expensive than the observed bundle. Our main result is that data sets can be rationalized by a smooth nontransitive preference relation if and only if prices can normalized such that the law of demand is satisfied. Market data sets consist of finitely...... many observations of price vectors, lists of individual incomes and aggregate demands. We apply our main result to characterize market data sets consistent with equilibrium behaviour of pure-exchange economies with smooth nontransitive consumers....

  7. Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanism.

    Science.gov (United States)

    Vemulapalli, S; Kurowski, S

    2001-02-01

    The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of the rabbit corpus cavernosum elicited frequency-related relaxation that was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of rabbit corpus cavernosum, suggesting that neuronal release of NO mediates relaxation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxation of the rabbit corpus cavernosum. Prazosin (30 microM) and yohimbine (30 microM) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit corpus cavernosum independent of alpha-adrenergic receptor blockade. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated electrical field stimulation produced relaxations to phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by activating NO synthase. The data suggest that phentolamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of alpha-adrenergic receptor blockade.

  8. Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis

    DEFF Research Database (Denmark)

    Siontis, George C M; Praz, Fabien; Pilgrim, Thomas

    2016-01-01

    AIMS: In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS...

  9. [Aortic valve replacement for the small aortic annulus].

    Science.gov (United States)

    Oshima, H; Usui, A; Akita, T; Ueda, Y

    2006-04-01

    Aortic valve surgery for the small aortic annulus is still challenging for surgeons. Recently, the new types of high performance prosthesis have been developed and the chance of an aortic root enlargement (ARE) is decreasing. In this study, we propose the ideal strategy of the aortic surgery for the small aortic annulus. We analyzed the clinical records of 158 patients who underwent aortic valve replacement from August 1999 to October 2005 in our institution. The small aortic annulus was observed in 38 patients (24%). Fourteen patients of this group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently observed in patients with ARE compared to those without ARE. The additional time required for ARE was not considerable, and neither ischemic time nor cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise we should choose an option of ARE. For this consideration, we definitely need the chart that demonstrates the relationship between the nominal size of various types of prostheses and the size of a patient's annulus that those prostheses actually fit.

  10. Balloon aortic valvuloplasty as a bridge to aortic valve replacement in a patient with severe calcific aortic stenosis.

    Science.gov (United States)

    Swinkels, B M; Jaarsma, W; Wely, L Relik-van; van Swieten, H A; Ernst, J M P G; Plokker, H W M

    2003-03-01

    This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high.

  11. Valve-sparing aortic root replacement and aortic valve repair in a patient with acromegaly and aortic root dilatation

    Directory of Open Access Journals (Sweden)

    Karel Van Praet

    2015-07-01

    Full Text Available Aortic regurgitation and dilatation of the aortic root and ascending aorta are severe complications of acromegaly. The current trend for management of an aortic root aneurysm is valve-sparing root replacement as well as restoring the diameter of the aortic sinotubular junction (STJ and annulus. Our case report supports the recommendation that in patients with acromegaly, severe aortic root involvement may indicate the need for surgery.

  12. Atherosclerosis induced by diabetogenic diet in New Zealand white rabbits

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To observe the effects of diabetogenic (high fat high sucrose, lacking choleserol) diet on atherogenesis in New Zealand white rabbits. Two groups of New Zealand white rabbits received regular rabbit chow (the normal control), or high fat high sucrose diet for 4 months. The levels of plasma total cholesterol, HDL cholesterol, triglycerides, insulin, and glucose were investigated, the areas of fatty streak of the aortae were measured after staining with Sodan IV, and the aortic, coronary specimens were observed with light and electron microscopies. The plasma glucose, triglycerides, and total cholesterol were increased significantly by high fat high sucrose feeding. At the end of 4 months, the early charateristics of atherosclerosis were present in the animals' vascular specimens. Our findings suggest that high fat high sucrose feeding can induce hyperglycemia, hypertriglyceridemia and atherosclerosis in New Zealand white rabbits, and this could be a potential animal model for studying the mechanisms of diabetes-accelerated atherosclerosis. This study raised a question: What is the mechanism by which high fat high sucrose feeding induces atherosclerosis?. The related hypothesis was given in this article.

  13. Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD)

    National Research Council Canada - National Science Library

    Pape, Linda A; Tsai, Thomas T; Isselbacher, Eric M; Oh, Jae K; O'gara, Patrick T; Evangelista, Arturo; Fattori, Rossella; Meinhardt, Gabriel; Trimarchi, Santi; Bossone, Eduardo; Suzuki, Toru; Cooper, Jeanna V; Froehlich, James B; Nienaber, Christoph A; Eagle, Kim A

    2007-01-01

    .... However, few studies of acute aortic dissection patients and aortic size exist. We used data from our registry of acute aortic dissection patients to better understand the relationship between aortic diameter and type A dissection...

  14. Aortic biomechanics in hypertrophic cardiomyopathy

    Science.gov (United States)

    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

  15. Intervention of Tongxinluo Capsule (通心络胶囊) against Vascular Lesion of Atherosclerosis and Its Effect on Lectin-like Oxidized Low Density Lipoprotein Receptor-1 Expression in Rabbits

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To investigate the prevention by Tongxinluo capsule ( 通心络胶囊, TXL) of vascular lesions and its effect on the levels of protein and gene expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in rabbits with atherosclerosis (AS), and to explore its possible mechanism against AS. Methods: AS models were established by feeding New Zealand white rabbits with high-cholesterol diet, and 24 immature rabbits were randomly divided into the control group, model group and treated group (treated with TXL capsule). The indexes of total cholesterol (TC) and low density lipoprotein (LDL) levels were measured at the 16th week. The intima thickness and the plaque area of abdominal aorta were quantitatively analyzed by pathological morphological analysis, the expression of macrophage and smooth muscle cell (SMC) in intima were detected by immunohistochemical method and histologic segments were stained by Hematoxilin-Eosin (HE) to identify the degree of atherosclerotic lesion in the model group and the prevention by TXL. The LOX-1 gene and protein expression in abdominal aorta was detected by semi-quantitative RT-PCR and immunohistochemistry, respectively. Results: In the model group, the levels of TC and LDL were significantly elevated, aortic intima thickened extensively, the intima area enhanced,and macrophages expression increased; the levels of LOX-1 gene and protein expression was up-regulated in endothelium and neo-intima of the abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial intimal proliferation, markedly inhibited the expression of macrophage and excessively expressed the level of LOX-1. Conclusion:TXL has an inhibitory effect on blood lipids, and it can prevent the occurrence of vascular lesion and cure its development , and its protection against AS was possibly associated with a crucial endothelial protective action through lowering the expression of LOX-1 in vascular walls.

  16. Increased expression of phosphorylated forms of heat-shock protein-27 and p38MAPK in macrophage-rich regions of fibro-fatty atherosclerotic lesions in the rabbit.

    Science.gov (United States)

    Shafi, Shahida; Codrington, Rosalind; Gidden, Lewis Michael; Ferns, Gordon Ashley Anthony

    2016-02-01

    We aimed to assess the expression and distribution of Hsp27, pHsp27 (Ser82), p38MAPK and p-p38MAPK in fibro-fatty atherosclerotic lesions and the myocardium of hypercholesterolaemic rabbits. Male New Zealand white rabbits were fed a high-cholesterol diet for 18 weeks, maintaining serum cholesterol at approximately 20 mmol/l over this period. Aortic arch and myocardial tissues were analysed by Western blot, immunohistochemistry and double immunofluorescence. Plasma Hsp27 levels were measured by ELISA. There was a significant increase in the expression of monomeric and dimeric forms of Hsp27, together with pHsp27 (Ser82), p38MAPK and p-p38MAPK in the fibro-fatty atherosclerotic lesions (P < 0.01; P < 0.05; P < 0.001; and P < 0.001, respectively) and the myocardial tissues (P < 0.001) from the cholesterol-fed rabbits compared with equivalent tissues from controls when the plasma concentration was low. Immunohistochemical analysis of the fibro-fatty lesions showed marked increases in Hsp27 and pHsp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pHsp27 and p-p38MAPK in regions that were rich in macrophages, suggesting a close association with these inflammatory cells, whereas, in regions rich in smooth muscle cells, only p-p38MAPK was found to be strongly expressed. An increased expression of pHsp27 (Ser82) was spatially associated with increased p-p38MAPK within fibro-fatty atherosclerotic lesions and was colocalized to regions rich in macrophages. The initial increase in plasma Hsp27 levels may reflect the increase in systemic inflammation and oxidative stress in the early phases of disease. The falling concentrations subsequently may be coincident with the development of the advanced atherosclerotic lesions.

  17. Smoothed Particle Hydrodynamic Simulator

    Energy Technology Data Exchange (ETDEWEB)

    2016-10-05

    This code is a highly modular framework for developing smoothed particle hydrodynamic (SPH) simulations running on parallel platforms. The compartmentalization of the code allows for rapid development of new SPH applications and modifications of existing algorithms. The compartmentalization also allows changes in one part of the code used by many applications to instantly be made available to all applications.

  18. Reinforced aortic root reconstruction for acute type A aortic dissection involving the aortic root

    Directory of Open Access Journals (Sweden)

    Han Qing-qi

    2013-06-01

    Full Text Available OBJECTIVE: There are debates regarding the optimal approach for AAAD involving the aortic root. We described a modified reinforced aortic root reconstruction approach for treating AAAD involving the aortic root. METHODS: A total of 161 patients with AAAD involving the aortic root were treated by our modified reinforced aortic root reconstruction approach from January 1998 to December 2008. Key features of our modified approach were placement of an autologous pericardial patch in the false lumen, lining of the sinotubular junction lumen with a polyester vascular ring, and wrapping of the vessel with Teflon strips. Outcome measures included post-operative mortality, survival, complications, and level of aortic regurgitation. RESULTS: A total of 161 patients were included in the study (mean age: 43.3 1 15.5 years. The mean duration of follow-up was 5.1 1 2.96 years (2-12 years. A total of 10 (6.2% and 11 (6.8% patients died during hospitalization and during follow-up, respectively. Thirty-one (19.3% patients experienced postoperative complications. The 1-, 3-, 5-, and 10-year survival rates were 99.3%, 98%, 93.8%, and 75.5%, respectively. There were no instances of recurrent aortic dissection, aortic aneurysm, or pseudoaneurysm during the entire study period. The severity of aortic regurgitation dramatically decreased immediately after surgery (from 28.6% to 0% grade 3-4 and thereafter slightly increased (from 0% to 7.2% at 5 years and 9.1% at 10 years. CONCLUSION: This modified reinforced aortic root reconstruction was feasible, safe and durable/effective, as indicated by its low mortality, low postoperative complications and high survival rate.

  19. An Important but Forgotten Technique: Aortic Fenestration.

    Science.gov (United States)

    Yalcin, Mihriban; Tayfur, Kaptan Derya; Urkmez, Melih

    2016-10-01

    Aortic fenestration is a technique that treats organ ischemia in descending aortic dissection. Open surgical aortic fenestration is an effective yet uncommonly used and widely forgotten procedure. Here, we describe 2 patients suffering from chronic thoracoabdominal aortic dissection, and we aimed to identify under what circumstances surgical aortic fenestration should be applied, to assess its safety and efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels.

    Science.gov (United States)

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

    2013-05-01

    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, while VIC expressed elevated vimentin. These results demonstrate that anatomically complex, heterogeneously encapsulated aortic valve hydrogel conduits can be fabricated with 3D bioprinting.

  1. Twins with progressive thoracic aortic aneurysm, recurrent dissection and ACTA2 mutation.

    Science.gov (United States)

    Ware, Stephanie M; Shikany, Amy; Landis, Benjamin J; James, Jeanne F; Hinton, Robert B

    2014-10-01

    Thoracic aortic aneurysm (TAA) is a genetically mediated disease with variable age of onset. In the pediatric age range, nonsyndromic TAA frequently has a milder course than syndromic forms of TAA, such as Marfan syndrome or Loeys-Dietz syndrome. Herein, we describe 17-year-old identical twin brothers with severe progressive TAA due to a novel de novo ACTA2 mutation. Interestingly, both boys were diagnosed at age 11 with congenital mydriasis, a recently recognized manifestation of some ACTA2 mutations due to smooth muscle dysfunction. One of the brothers presented with acute-onset lower back pain that was identified as dissection of an abdominal aortic aneurysm. Imaging of the chest at this time showed severe fusiform TAA. Cardiac imaging in his twin showed similar TAA, but no abdominal aortic aneurysm. Both brothers underwent valve-sparing aortic root replacement, but have had progressive aortic disease with recurrent dissection requiring multiple surgeries. This case emphasizes the importance of identifying physical stigmata of smooth muscle dysfunction, such as mydriasis, as potential markers for associated aortopathy and vascular diseases. Copyright © 2014 by the American Academy of Pediatrics.

  2. Contractile effect of tachykinins on rabbit small intestine

    Institute of Scientific and Technical Information of China (English)

    Marta Sofía VALERO; Diego Santos FAGUNDES; Laura GRASA; María Pilar ARRUEBO; Miguel (A)ngel PLAZA; María Divina MURILLO

    2011-01-01

    Aim:To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P(SP).Methods:Rabbit duodenum,jejunum and ileum segments were prepared.The spontaneous contractions of longitudinal and circular smooth muscle were recorded using a computer via an isometric force transducer.The specific agonists and antagonists of tachykinin receptors were added into the organ bath.Results:The agonists of tachykinin NKl receptor(SP and[Sar9]SP).NK2 receptor(NKA and(β-Ala8)-NKA),and NK3 receptor(NKBand Senktide)all induced contractions in the small intestine.The contractions were diminished bv NKl receptor antagonist L-733.060,NK2 receptor antagonist GR-94800, and NK3 receptor antagonist SB 218795.Contractions caused by SP were also reduced by atropine, verapamil, PKC inhibitor staurosporine, and PLC Inhibitor U73122.Conclusion:Ttachykinin NKl,NK2, and NK3 receptors mediate the contractions of the smooh muscle in rabbit intestine.Furthermore,SP acts directly on smooth muscle cells through the tachykinin NK1 receptor.

  3. Role of Microvascular Tone and Extracellular Matrix Contraction in the Regulation of Interstitial Fluid: Implications for Aortic Dissection.

    Science.gov (United States)

    Mallat, Ziad; Tedgui, Alain; Henrion, Daniel

    2016-09-01

    The pathophysiology of aortic dissection is poorly understood, and its risk is resistant to medical treatment. Most studies have focused on a proposed pathogenic role of transforming growth factor-β in Marfan disease and related thoracic aortic aneurysms and aortic dissections. However, clinical testing of this concept using angiotensin II type 1 receptor antagonists to block transforming growth factor-β signaling fell short of promise. Genetic mutations that predispose to thoracic aortic aneurysms and aortic dissections affect components of the extracellular matrix and proteins involved in cellular force generation. Thus, a role for dysfunctional mechanosensing in abnormal aortic wall remodeling is emerging. However, how abnormal mechanosensing leads to aortic dissection remains a mystery. Here, we review current knowledge about the regulation of interstitial fluid dynamics and myogenic tone and propose that alteration in contractile force reduces vascular tone in the microcirculation (here, aortic vasa vasorum) and leads to elevations of blood flow, transmural pressure, and fluid flux into the surrounding aortic media. Furthermore, reduced contractile force in medial smooth muscle cells coupled with alteration of structural components of the extracellular matrix limits extracellular matrix contraction, further promoting the formation of intramural edema, a critical step in the initiation of aortic dissection. The concept is supported by several pathophysiological and clinical observations. A direct implication of this concept is that drugs that lower blood pressure and limit interstitial fluid accumulation while preserving or increasing microvascular tone would limit the risk of dissection. In contrast, drugs that substantially lower microvascular tone would be ineffective or may accelerate the disease and precipitate aortic dissection.

  4. Expression of Slit3/Robo signal pathway in mouse aortic smooth muscle cell and its impact on proliferation and migration%Slit3/Robo信号通路在小鼠主动脉平滑肌细胞的表达及其对细胞增殖和迁移的作用

    Institute of Scientific and Technical Information of China (English)

    倪伟; 刘涛; 王浩宇; 刘丽华; 陈桂秀

    2016-01-01

    Objective To observe the expression of neural axon guidance molecules Slit3 and Robo receptors in mouse aortic smooth muscle cell(MASMC) and investigate the effect of exogenous Slit3 protein on migration and proliferation of MASMC.Methods The primary cultured MASMC were identified by immunofluorescent assay.The expression of Slit3/Robo signal pathway was detected by RT-PCR and immunocytochemical staining.MASMC were divided into 6 groups:the negative control group (DMEM medium containing bovine serum albumin 86 μg/L),Slit3 0μg/L group (DMEM medium without Slit3),Slit3 24 μg/L group (DMEM medium containing Slit3 24 μg/L),Slit3 40 μg/L group (DMEM medium containing Slit3 40 μg/L),Slit3 80 μg/L group (DMEM medium containing Slit3 80 μg/L) and the positive control group (DMEM medium containing platelet derived growth factor 10 μg/L).The effects of exogenous Slit3 on MASMC proliferation and migration were detected by CCK-8 and scratched cells and transwell chambers respectively.Results (1) The mRNA and protein expressions of Slit2,Slit3,Robo1 and Robo4 were detected in MASMC.mRNA level of Slit2 was lower than Slit3 (P < 0.05) and there were no significant difference between mRNA level of Robo1 and Robo4.(2) The mitogenic responses of MASMC were significantly enhanced in Slit3 24 μg/L group,Slit3 40 μg/L group and Slit3 80 μg/L group compared with negative control group (1.13 ± 0.04,1.19 ± 0.02,1.18 ± 0.08 and 0.64 ± 0.10 respectively,all P <0.05).The mitogenic activity of MASMC was the strongest in Slit3 40 μg/L group (compared with positive control group 1.27 ± 0.05,P > 0.05).(3) The autonomous migration activity of MASMC were significantly increased in Slit3 24 μg/L group,Slit3 40 μg/L group,Slit3 80 μg/L group compared with negative control group (cell scratch width were (0.40 ± 0.03) cm,(0.32 ± 0.03) cm,(0.30 ± 0.02) cm and (0.49 ±0.01) cm respectively,all P < 0.05).The autonomous migration activity of MASMC was the strongest in Slit3

  5. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, S.A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates. Dut

  6. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

  7. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

  8. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

    NARCIS (Netherlands)

    Burt, S.A.|info:eu-repo/dai/nl/140114432; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H.M.

    2016-01-01

    Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

  9. Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

    Science.gov (United States)

    Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

    2015-02-25

    Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. Abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal

    2010-01-01

    Although the number of elective operations for abdominal aortic aneurysms (AAA) is increasing, the sex- and age-standardised mortality rate of AAAs continues to rise, especially among men aged 65 years or more. The lethality of ruptured AAA continues to be 80-95%, compared with 5-7% by elective...... inhibit further AAA progression. All 4 existing RCTs point in the same direction, viz. in favour of screening of men aged 65 and above. We found that screening significantly reduced AAA-related mortality by 67% within the first five years (NNT = 352). Restriction of screening to men with previous...... year gained was 157 euro [1,170 DKK] and the cost per QALY at 178 euro [1,326 DKK]. In all, the ethical dilemma of the prophylactic operation, and the limited psychological side effects seem not to outweigh the benefits of screening. Conclusively, we found that offering men aged 65-73 years screening...

  11. Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9.

    Science.gov (United States)

    Lupia, Enrico; Zheng, Feng; Grosjean, Fabrizio; Tack, Ivan; Doublier, Sophie; Elliot, Sharon J; Vlassara, Helen; Striker, Gary E

    2012-02-01

    Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.

  12. Smooth Neighborhood Structures in a Smooth Topological Spaces

    Directory of Open Access Journals (Sweden)

    A. A. Ramadan

    2010-01-01

    Full Text Available Various concepts related to a smooth topological spaces have been introduced and relations among them studied by several authors (Chattopadhyay, Ramadan, etc. In this study, we presented the notions of three sorts of neighborhood structures of a smooth topological spaces and give some of their properties which are results by Ying extended to smooth topological spaces.

  13. Aortic and Pulmonary Root Aneurysms in a Child With Loeys-Dietz Syndrome.

    Science.gov (United States)

    Rizzo, Stefania; Stellin, Giovanni; Milanesi, Ornella; Padalino, Massimo; Vricella, Luca A; Thiene, Gaetano; Cameron, Duke E; Basso, Cristina; Vida, Vladimiro L

    2016-03-01

    We report the case of an 11-year-old boy with Loeys-Dietz syndrome, with both aortic and pulmonary aneurysms requiring cardiac operation because of progressive valve incompetence resulting from loss of coaptation of the cusps. Arterial medial changes, consisting of disarray of elastic fibers and increased collagen deposition, were observed in surgical specimens from both the aorta and the pulmonary artery of our patient, and the strong pSmad2 nuclear staining of smooth muscle cells of both aortic and pulmonary tunica media are the best evidence of transforming growth factor-β pathway activation in Loeys-Dietz syndrome.

  14. Transcatheter Aortic Heart Valve Thrombosis

    DEFF Research Database (Denmark)

    Hansson, Nicolaj C; Grove, Erik L; Andersen, Henning R;

    2016-01-01

    BACKGROUND: There is increasing focus on transcatheter heart valve (THV) thrombosis. However, there are limited data on incidence, clinical implications and predisposing factors of THV thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: We assessed the incidence...

  15. Adult thoracic and abdominal aortic

    Directory of Open Access Journals (Sweden)

    Randa O. Kaddah

    2016-06-01

    Conclusion: Aortic COA could be found in any segment of the aorta. Proper identification of the anatomical details and pressure gradient studies are important factors affecting the plan of management.

  16. CONGENITAL QUADRICUSPID AORTIC-VALVE

    NARCIS (Netherlands)

    BROUWER, MHJ; DEGRAAF, JJ; EBELS, T

    1993-01-01

    Two patients with a quadricuspid aortic valve are described, one of them with concomitant juxtaposed coronary orifices facing the right hand facing sinus. The etiology and incidence of this congenital anomaly will be discussed.

  17. Minimally invasive aortic valve replacement

    DEFF Research Database (Denmark)

    Foghsgaard, Signe; Schmidt, Thomas Andersen; Kjaergard, Henrik K

    2009-01-01

    In this descriptive prospective study, we evaluate the outcomes of surgery in 98 patients who were scheduled to undergo minimally invasive aortic valve replacement. These patients were compared with a group of 50 patients who underwent scheduled aortic valve replacement through a full sternotomy....... The 30-day mortality rate for the 98 patients was zero, although 14 of the 98 mini-sternotomies had to be converted to complete sternotomies intraoperatively due to technical problems. Such conversion doubled the operative time over that of the planned full sternotomies. In the group of patients whose...... is an excellent operation in selected patients, but its true advantages over conventional aortic valve replacement (other than a smaller scar) await evaluation by means of randomized clinical trial. The "extended mini-aortic valve replacement" operation, on the other hand, is a risky procedure that should...

  18. Smoothness of limit functors

    Indian Academy of Sciences (India)

    Benedictus Margaux

    2015-05-01

    Let be a scheme. Assume that we are given an action of the one dimensional split torus $\\mathbb{G}_{m,S}$ on a smooth affine -scheme $\\mathfrak{X}$. We consider the limit (also called attractor) subfunctor $\\mathfrak{X}_{}$ consisting of points whose orbit under the given action `admits a limit at 0’. We show that $\\mathfrak{X}_{}$ is representable by a smooth closed subscheme of $\\mathfrak{X}$. This result generalizes a theorem of Conrad et al. (Pseudo-reductive groups (2010) Cambridge Univ. Press) where the case when $\\mathfrak{X}$ is an affine smooth group and $\\mathbb{G}_{m,S}$ acts as a group automorphisms of $\\mathfrak{X}$ is considered. It also occurs as a special case of a recent result by Drinfeld on the action of $\\mathbb{G}_{m,S}$ on algebraic spaces (Proposition 1.4.20 of Drinfeld V, On algebraic spaces with an action of $\\mathfrak{G}_{m}$, preprint 2013) in case is of finite type over a field.

  19. Anti-smooth muscle antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the ...

  20. WEIGHTS or RABBITS

    African Journals Online (AJOL)

    heart and spleen from_male and femalerabbits were made, in rabbits fed graded levels (0, 4, 8, 12%) of oil palm indiets. ..... aeetyl CoA derived mainly from carbohydrate wasdepressed ... an integral part in the synthesis and metabolism of.

  1. A Clever Rabbit

    Institute of Scientific and Technical Information of China (English)

    呼振璞; 付晓明

    2002-01-01

    1. Once there lived an elephant and a lion in the mountains, who both wanted to be the king of the beasts. One day the lion caught a rabbit. Before he ate it, he said, “Do you know I am the king here? ”

  2. Rabbit Repellent Paint

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Five gallons of rabbit repellent paint were sent to George Wilson to be applied on the trees of the Tewaukon tree plot. Mr. Wilson requires a 3 or 4 in. brush for...

  3. The Cutaneous Rabbit Revisited

    Science.gov (United States)

    Flach, Rudiger; Haggard, Patrick

    2006-01-01

    In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE…

  4. Smooth muscle cell phenotype modulation and contraction on native and cross-linked polyelectrolyte multilayers.

    Science.gov (United States)

    Moussallem, Maroun D; Olenych, Scott G; Scott, Shannon L; Keller, Thomas C S; Schlenoff, Joseph B

    2009-11-09

    Smooth muscle cells convert between a motile, proliferative "synthetic" phenotype and a sessile, "contractile" phenotype. The ability to manipulate the phenotype of aortic smooth muscle cells with thin biocompatible polyelectrolyte multilayers (PEMUs) with common surface chemical characteristics but varying stiffness was investigated. The stiffness of (PAH/PAA) PEMUs was varied by heating to form covalent amide bond cross-links between the layers. Atomic force microscopy (AFM) showed that cross-linked PEMUs were thinner than those that were not cross-linked. AFM nanoindentation demonstrated that the Young's modulus ranged from 6 MPa for hydrated native PEMUs to more than 8 GPa for maximally cross-linked PEMUs. Rat aortic A7r5 smooth muscle cells cultured on native PEMUs exhibited morphology and motility of synthetic cells and expression of the synthetic phenotype markers vimentin, tropomyosin 4, and nonmuscle myosin heavy chain IIB (nmMHCIIB). In comparison, cells cultured on maximally cross-linked PEMUs exhibited the phenotype markers calponin, smooth muscle myosin heavy chain (smMHC), myocardin, transgelin, and smooth muscle alpha-actin (smActin) that are characteristic of the smooth muscle "contractile" phenotype. Consistent with those cells being "contractile", A7r5 cells grown on cross-linked PEMUs produced contractile force when stimulated with a Ca(2+) ionophore.

  5. EMBEDDING FLOWS AND SMOOTH CONJUGACY

    Institute of Scientific and Technical Information of China (English)

    ZHANGMEIRONG; LIWEIGU

    1997-01-01

    The authors use the functional equation for embedding vector fields to study smooth embedding flows of one-dimensional diffeomorphisms. The existence and uniqueness for smooth embedding flows and vector fields are proved. As an application of embedding flows, some classification results about local and giobal diffeomorphisms under smooth conjugacy are given.

  6. [New aspects in aortic valve disease].

    Science.gov (United States)

    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.

  7. In vivo non-invasive serial monitoring of FDG-PET progression and regression in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Worthley, Stephen G; Zhang, Zhuang Y; Machac, Josef; Helft, Gérard; Tang, Cheuk; Liew, Gary Y H; Zaman, Azfar G; Worthley, Matthew I; Fayad, Zahi A; Buchsbaum, Monte S; Fuster, Valentin; Badimon, Juan J

    2009-03-01

    We investigated the ability of fluorodeoxyglucose positron emission tomography (FDG PET) imaging to serially monitor macrophage content in a rabbit model of atherosclerosis. Atherosclerosis was induced in rabbits (n = 8) by a combination of atherogenic diet and balloon denudation of the aorta. At the end of nine months, the rabbits were randomized to a further six months of the same atherogenic diet (progression group) or normal diet (regression group). In vivo uptake of FDG by the thoracic aorta was measured using aortic uptake-to-blood radioactivity ratios at the start and end of the randomized period. A significant increase in FDG uptake of the progression group after continued cholesterol feeding (aortic uptake-to-blood radioactivity: 0.57 +/- 0.02 to 0.68 +/- 0.02, P = 0.001), and a corresponding fall in FDG uptake of the regression group after returning to a normal chow diet (aortic uptake-to-blood radioactivity ratios: 0.67 +/- 0.02 to 0.53 +/- 0.02, P < 0.0001). FDG PET can quantify in vivo macrophage content and serially monitor changes in FDG activity in this rabbit model.

  8. Influence of baroreflex on volume elasticity of heart and aorta in the rabbit.

    Science.gov (United States)

    Wronski, T; Seeliger, E; Persson, P B; Harnath, A; Flemming, B

    2002-03-01

    Optimal ventriculoaortic coupling includes tuning of elastic properties. The ratio of effective arterial elastance and left ventricular endsystolic elastance is often taken as a measure for mechanical and energetical efficiency. The present study determined the time course of ventricular and aortic volume elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by using changes of eigenfrequency of two catheter-transducer systems under closed chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex response, as induced by pressure changes applied to the carotid sinus. Long-term changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol feeding). The time course and mean values of ventricular and aortic VE were changed by the baroreflex stimulus. Cholesterol feeding diminished the response. The degree of ventriculoaortic coupling, as quantified by VE(Aorta)/VE(Ventricle) ratio, varied during a single ejection period. The large span allows either maximal energetical efficiency or maximal stroke work. Although normal rabbits adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol-fed rabbits failed to do so.

  9. Vasorelaxation Effect of Estrone Derivate EA204 in Rabbit Aorta

    Directory of Open Access Journals (Sweden)

    Juan Li

    2016-01-01

    Full Text Available Estrogen and its derivatives exert vascular protective effects, but the underlying mechanisms remain to be studied fully. Objective. To investigate the vasorelaxation effect and related mechanisms of an estrone derivate EA204[3-(2-piperidin-1-yl-ethoxy-estra-1, 3, 5 (10-trien-17-one] on isolated arterial preparation from rabbit thoracic aorta. Methods. Aortic rings from rabbit thoracic aorta were prepared and held in small organ bath filled with Krebs solution; tension change was recorded by a multichannel physiological signal collection and handling system. Results. EA204 (10−5 to 10−3 M induced a concentration-dependent relaxation of aortic rings with endothelium and without endothelium. In denuded arterial preparations, EA204 had a potent relaxing effect on isolated arterial preparations contracted with phenylephrine, norepinephrine, and high-K+ solution or BaCl2. Mechanism study indicates that EA204 relaxes aortic rings by inhibiting Ca2+ channels (both receptor-operating Ca2+ channels and the voltage-dependent Ca2+ channels were involved to decrease extracellular Ca2+ influx and intracellular Ca2+ release. EA204 is different from verapamil, which is a noncompetitive inhibitor of Ca2+ channels. In addition, K+ channels opening may contribute to this vasorelaxation effect. Conclusion. EA204 had a potent endothelium-independent relaxing effect on isolated arterial preparation by inhibiting Ca2+ channels and opening K+ channels. The results suggest that EA204 is a potential compound for treatment of cardiovascular diseases in postmenopausal women.

  10. Palmitate induces monocyte chemoattractant protein-1 expression in human aortic vascular smooth muscle cells via toll like receptor 4 signaling pathway%果蝇样受体4介导游离脂肪酸调节人血管平滑肌细胞单核细胞趋化蛋白-1的表达

    Institute of Scientific and Technical Information of China (English)

    高啸波; 权金星; 杨海静; 陈卫; 李伟华; 李永红; 刘静

    2013-01-01

    +parthenolide组、软脂酸+白屈菜红碱组、软脂酸+ wortmannin组和软脂酸+myriocin组MCP-1 mRNA表达分别为1.00±0.02、10.80±1.23、3.49±0.28、10.84±0.24、11.24±0.27和10.62±0.36(F=1313.07,P<0.05);MCP-1蛋白表达分别为(132±8)、(218±12)、(152±4)、(213±12)、(225±7)和(226±9)ng/L(F=106.83,P<0.05).成功地构建并获得TLR4 shRNA腺病毒pGSadeno-TLR4,采用pGSadeno-TLR4感染HA-VSMC阻断TLR.信号后,软脂酸+pGSadeno-TLR4组的NF-κBp65结合活性、MCP-1 mRNA和蛋白表达均显著低于软脂酸组[分别为0.48±0.12比1.24±0.16、1.88±0.33比10.80±1.23、(154±10)比(218±12)ng/L;F =591.86、659.16、118.37,均P<0.01].而对照病毒pGSadeno-GFP对软脂酸诱导的NF-κB p65结合活性和MCP-1表达均无明显影响.结论 TLR4/NF-κB信号通路介导了软脂酸诱导的人主动脉血管平滑肌细胞MCP-1基因表达.%Objective To investigate the role of toll like receptor 4(TLR4)pathway in regulation of monocyte chemoattractant protein-1(MCP-1)by palmitate in human aortic vascular smooth muscle cells (HA-VSMC).Methods To study the time course and dose dependent effects of palmitate on MCP-1 gene expression,HA-VSMC were cultured and treated with 100,200 or 400 μ mol/L of palmitate for 6,12 or 24 h,cells were then harvested at indicated time points,MCP-1 mRNA expression was analyzed with realtime polymerase chain reaction(RT-PCR)and the production of MCP-1 protein in cultural supernatant were tested using enzyme-linked immunosorbent assay(ELISA).To determine the involvement of signaling pathways in regulation of MCP-1 by palmitate,specific inhibitors that block protein kinase C(PKC),phosphotylinosital 3 kinase(PI3K),ceramide or nuclear factor(NF)-κB signaling were added to the serumfree media for 30 min followed by treatment with or without 400 μ mol/L of palmitate for additional 6 h,thereafter,the mRNA and protein expression of MCP-1 were studied.To further clarify the role of TLR4 pathway in induction of MCP-1

  11. Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

    Science.gov (United States)

    Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

    2015-09-01

    The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans.

  12. Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.

    Directory of Open Access Journals (Sweden)

    Yafeng Li

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

  13. Effect of tadalafil in chronic renal failure rabbits: relevance to erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Meng-yuan ZHANG; Qiang FU; Wei BIAN

    2011-01-01

    It is of great importance to investigate an effective and reliable medication against chronic renal failure (CRF)-related erectile dysfunction (ED), which aims to improve patients' life qualities. The concentrations of cyclic guanosine monophosphate (cGMP) in the corpus cavernosal smooth muscle of both CRF and control rabbits were measured. The effects of various concentrations of tadalafil, papaverine, and sodium nitroprusside on the relaxation responses of corpus cavernosal smooth muscle pre-contracted with phenylephrine in CRF rabbits were observed. There was significant difference in the concentration of cGMP between CRF and control rabbits (P<0.01). Tadalafil had the greatest impacts on CRF rabbits when given the same concentration of papaverine or sodium nitroprusside and particularly significant differences were identified under the concentration levels of 10-5 and 10-4 mol/L (P<0.01). The results suggest that the cGMP concentrations of the corpus cavernosum had been greatly reduced in CRF rabbits compared with control rabbits and that tadalafil may be an ideal medication for use in the treatment of CRF-related ED.

  14. Spontaneous aortic dissection within an infrarenal AAA.

    Science.gov (United States)

    Griffin, Kathryn J; Bailey, Marc A; McAree, Barry; Mekako, Anthony; Berridge, David C; Nicholson, Tony; Scott, D Julian A

    2012-12-01

    Aortic dissection occurring in the infrarenal abdominal aorta is uncommon. We present the case of a patient presenting with an enlarging abdominal aortic aneurysm and concurrent dissection (with associated radiological imaging) and briefly discuss the literature relating to this phenomenon.

  15. Abdominal aortic aneurysm repair - open - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000240.htm Abdominal aortic aneurysm repair - open - discharge To use the sharing features ... References Orandi BJ, Black JH. Open repair of abdominal aortic aneurysms. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  16. Abdominal aortic feminism.

    Science.gov (United States)

    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. 2014 BMJ Publishing Group Ltd.

  17. IP3 receptors regulate vascular smooth muscle contractility and hypertension

    Science.gov (United States)

    Lin, Qingsong; Zhao, Guiling; Fang, Xi; Peng, Xiaohong; Tang, Huayuan; Wang, Hong; Jing, Ran; Liu, Jie; Ouyang, Kunfu

    2016-01-01

    Inositol 1, 4, 5-trisphosphate receptor–mediated (IP3R-mediated) calcium (Ca2+) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle–specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca2+ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP3Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP3Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP3R-mediated Ca2+ release in VSMCs in regulating vascular contractility and hypertension.

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

    Science.gov (United States)

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

    2016-05-01

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

  19. Management of bicuspid aortic valve with or without involvement of ascending aorta and aortic root.

    Science.gov (United States)

    Neragi-Miandoab, S

    2014-06-01

    Patients with a bicuspid aortic valve (BAV) constitute a heterogeneous population with variable clinical presentation and complications. More than 50% of the patients who require aortic valve replacement have a BAV, a condition that may be associated with dilation of ascending aorta and aortic insufficiency caused by cusp disease or aortic root pathology. Of the potential BAV-related complications, dilation of the aortic root and ascending aorta are among the most serious. The dilation of ascending aorta and aortic root have been the subject of controversy. Whereas some surgeons believe that the dilation of the aorta is caused by the hemodynamic properties of the BAV, others believe that the dilation of the aortic root is secondary to genetic defects associated with the BAV. Management of a BAV should be tailored to each patient's clinical condition. The surgical approach varies from aortic valve replacement to combined aortic valve and root replacement to aortic-valve-sparing root replacement.

  20. The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm.

    Science.gov (United States)

    Li, Jiaze; Krishna, Smriti Murali; Golledge, Jonathan

    2016-08-11

    Abdominal aortic aneurysm (AAA) is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α) signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF) and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.

  1. The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Jiaze Li

    2016-08-01

    Full Text Available Abdominal aortic aneurysm (AAA is a vascular condition that causes permanent dilation of the abdominal aorta, which can lead to death due to aortic rupture. The only treatment for AAA is surgical repair, and there is no current drug treatment for AAA. Aortic inflammation, vascular smooth muscle cell apoptosis, angiogenesis, oxidative stress and vascular remodeling are implicated in AAA pathogenesis. Kallistatin is a serine proteinase inhibitor, which has been shown to have a variety of functions, potentially relevant in AAA pathogenesis. Kallistatin has been reported to have inhibitory effects on tumor necrosis factor alpha (TNF-α signaling induced oxidative stress and apoptosis. Kallistatin also inhibits vascular endothelial growth factor (VEGF and Wnt canonical signaling, which promote inflammation, angiogenesis, and vascular remodeling in various pre-clinical experimental models. This review explores the potential protective role of kallistatin in AAA pathogenesis.

  2. Laparoscopic ovariectomy in rabbits

    Directory of Open Access Journals (Sweden)

    M. S. Al-Badrany

    2009-01-01

    Full Text Available A comparative evaluation of three different techniques of laparoscopic ovariectomy was carried out in 33 healthy female in rabbits, which included resection and removal of ovary after clip application, electrocautery of the ovary, then resection, and pulling ovary outside abdomen, ligation by silk, then ovary was removed. The ovaries and associated structures were better visualized by laparoscopy and all three techniques were carried out perfectly. All rabbits after operation were healthy and they were monitored for one month after operation. However, 3 of them died after operation, two of them died due to bleeding and the other of them died due to unknown causes. General anesthesia by using ketamine-xylazine i.m., was suitable for this technique, and the anesthesia provided good analgesia and good muscle relaxation. CO2 was used to establish pneumoperitoneum. In conclusion, resection and removal of the ovaries after clip application technique was found superior to the other two techniques.

  3. Thoracic aortic aneurysm: A rare cause of elevated hemidiaphragm

    Directory of Open Access Journals (Sweden)

    Md Arshad Ejazi

    2016-01-01

    Full Text Available Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of thoracic aortic aneurysm. In one case, a 30 year male complained of chronic dull aching chest pain, and hoarseness of voice; posteroanterior view chest radiograph revealed large spherical radiopacity on the left upper lung zone with smooth lobulated margin with elevated left hemidiaphragm. On Colour Doppler sonography, lesion was anechoic on gray scale sonography but on Doppler analysis revealed intense internal vascularity within it with characteristic "Ying Yang" sign. The finding favor the vascular origin of the lesion and a diagnosis of an arterial aneurysm was made Contrast-enhanced computed tomography (CT of the thorax revealed a large well defined spherical lesion of 8 × 10 cm size with smooth well defined margin arising from the aortic arch and attenuation of impending rupture or dissection were lesion on immediate post contrast and delayed scan was similar to that of aorta. Left hemidiaphragm elevation was explained by the gross mass effect of the aneurysm causing right phrenic nerve palsy.

  4. Open aortic surgery after thoracic endovascular aortic repair.

    Science.gov (United States)

    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.

  5. Correlation of histological findings with gadolinium enhanced MRI scans during healing of a PHEMA orbital implant in rabbits

    OpenAIRE

    Hicks, C.; Morris, I.; Vijayasekaran, S; Fallon, M.; McAllister, J.; Clayton, A.; Chirila, T.; Crawford, G; Constable, I

    1999-01-01

    BACKGROUND/AIMS—To investigate a poly(2-hydroxyethyl methacrylate) (PHEMA) orbital implant with a spongy anterior hemisphere and a smooth gel posterior hemisphere, by histology correlated with magnetic resonance images.
METHODS—Following enucleation, eight rabbits received PHEMA implants to which the muscles were directly sutured, and underwent gadolinium enhanced magnetic resonance imaging (MRI) from 3 to 52 weeks. After the rabbits were killed, the implants were removed, cut in a plane corr...

  6. The researchers developed luminous rabbit

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>Their efforts produced two rabbits out of a litter of eight that went from being a normal, fluffy(蓬松的) white to glowing green in the dark. The rabbits were born at the University of Istanbul as part of a collaboration between scientists from universities in Turkey and Hawaii. The rabbits glow to show that a genetic manipulation technique can work efficiently,

  7. Contractile proteins of endothelial cells, platelets and smooth muscle.

    Science.gov (United States)

    Becker, C G; Nachman, R L

    1973-04-01

    In experiments described herein it was observed, by direct and indirect immunofluorescence technics, that rabbit antisera to human platelet actomyosin (thrombosthenin) stained mature megakaryocytes, blood platelets, endothelial cells and smooth muscle cells of arteries and veins, endothelial cells of liver sinusoids and certain capillaries, uterine smooth muscle cells, myoepithelial cells, perineurial cells of peripheral nerves and "fibroblastic" cells of granulation tissue. The specificity of immunohistologic staining was confirmed by appropriate absorption and blocking studies and immunodiffusional analysis in agarose gel. It was also observed by immunodiffusional analysis in agarose gel, electrophoresis of actomyosin fragments in polyacrylamide gels, immune inhibition of actomyosin ATPase activity and immune aggregation of platelets that uterine and platelet actomyosin are partially, but not completely, identical.

  8. Icariin on relaxation effect of corpus cavernosum smooth muscle

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    NO-cGMP pathway in penile corpus cavernosal smooth muscle plays an important role in penile erection. The level of cGMP is regulated by a balance between the rate of synthesis by guanylate cyclase and the rate of hydrolytic breakdown to guanosine 5′monophosphate (GMP) by phos- phodiesterase 5(PDE5). Icariin is isolated from natural drug Epimedii herba, it is shown to have the relaxation effect on corpus cavernosal smooth muscle of rabbit (IC50: 4×10-4 mol/L), and the mechanism of the relaxation effect of Icariin on corpus cavernosum believed to have the inhibiting effect on PDE5 and activation of NO-cGMP pathway to enhancing penile erection.

  9. Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Mariann Bombicz

    2016-08-01

    Full Text Available The present investigation evaluates the capacity of Allium ursinum (wild garlic leaf lyophilisate (WGLL; alliin content: 0.261% to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i cholesterol-free rabbit chow (control; (ii rabbit chow containing 2% cholesterol (hypercholesterolemic, HC; (iii rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT; for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders.

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

    Science.gov (United States)

    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

  11. Aortic root replacement with a pulmonary autograft

    NARCIS (Netherlands)

    R.B. Hokken (Raymond)

    1997-01-01

    textabstractAortic valve disease in the pediatric age group is usually a consequence of congenital aortic stenosis, which may be isolated or may be a part of an anomaly of the left ventricular outflow tract or the aortic root. Management of these patients is difficult. Neonates and infants with seve

  12. Reconstruction of rabbit urethra using urethral extracellular matrix

    Institute of Scientific and Technical Information of China (English)

    杨嗣星; 姚颐; 胡云飞; 宋超; 王玲珑; 金化民

    2004-01-01

    Background Urethral reconstruction for both congenital and acquired etiologies remains a challenge for most urologic surgeons. Tissue engineering has been proposed as a strategy for urethral reconstruction. The purpose of This study was to determine whether a naturally derived extracellular matrix substitute developed for urethral reconstruction would be suitable for urethral repair in an animal model.Methods A urethral segmental defect was created in 20 male rabbits. The urethral extracellular matrix, obtained and processed from rabbit urethral tissue, was trimmed and transplanted to repair the urethral defect. Then, the regenerated segment was studied histologically by haematoxylin-eosin staining and Van Gieson staining at 10 days, 3 weeks, 6 weeks, and 24 weeks postoperation. Retrograde urethrography was used to evaluate the function of the regenerated urethras of 4 rabbits 10 and 24 weeks after the operation. The urodynamics of 4 rabbits from the experimental group and control group Ⅰ were assessed and compared. In addition, 4 experimental group rabbits were examined by a urethroscope 24 weeks after the operation.Results At 10 days after operation, epithelial cells had migrated from each side, and small vessels were observed in the extracellular matrix. The matrix and adjacent areas of the host tissue were infiltrated with inflammatory cells. The epithelium covered the extracellular matrix fully at 3 weeks postoperation. Well-formed smooth-muscle cells were first confirmed after 6 weeks, at which point the inflammatory cells had disappeared. At 24 weeks postoperation, the regenerated tissue was equivalent to the normal urethra. Urethrography and urodynamic evaluations showed that there was no difference between normal tissue and regenerated tissue.Conclusions Urethral extracellular matrix appears to be a useful material for urethral repair in rabbits. The matrix can be processed easily and has good characteristics for tissue handling and urethral function.

  13. Nanostructure of Human Aortic Intima in Atherosclerosis (A Pilot Study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2016-01-01

    Full Text Available Objective: to analyze the nanostructure of human aortic intima in atherosclerosis and demonstrate the poten tial effect of Niodex on cholesterol plaques.Materials and methods. Samples of intima were taken from those parts of aorta, where different stages of atherosclerotic chages were obvious. Aortic samples were incubated in a solution containing cyclodextrins. A solution of NIODEX, a propylene glycol ester of betacyclodextrin, was used in the study. A layer of aortic intima was formed on the glass slide surface with polylysine. The samples were placed into the working area of an atomicforce microscope (Integra Prima, NTMDT, Russian Federation, and their surfaces were scanned. The number of imaging points was 512; and the imaging regions were as follows: 100100 μm, 20002000 nm.Results. Classification of nanosurface objects was performed and typical fragments (craters, ridges, and trabecular fibers were identified, and quantitative assessment of their sizes was carried out. 27 fragments were identified as growing cholesterol plaques. 16 of them measuring 900—1200 nm were identified near ridges, and 11 near craters (600—1050 nm. Niodex caused destruction of lipid spots and smoothing of the intima surface. More than a half of the 27 identified objects (15 demostrated a 30% and more decrease in size (median 340—400 nm. A 10—15% decrease was registered in 7 fragments; in the remaining 5 fragments, the decrease in the lesion size was less than 10%.Conclusion. Raw data permit to suppose that the effect of Niodex on the aortic intima results in decceleartion and decreased intensity of atherosclerotic plaque growth on the intima fragments.

  14. [MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT].

    Science.gov (United States)

    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.

  15. Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits.

    Science.gov (United States)

    Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ibrahim, Muhammad

    2017-06-01

    Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (Pjuice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Classification of smooth Fano polytopes

    DEFF Research Database (Denmark)

    Øbro, Mikkel

    Fano polytopes up to isomorphism. A smooth Fano -polytope can have at most vertices. In case of vertices an explicit classification is known. The thesis contains the classification in case of vertices. Classifications of smooth Fano -polytopes for fixed exist only for . In the thesis an algorithm...... for the classification of smooth Fano -polytopes for any given is presented. The algorithm has been implemented and used to obtain the complete classification for .......A simplicial lattice polytope containing the origin in the interior is called a smooth Fano polytope, if the vertices of every facet is a basis of the lattice. The study of smooth Fano polytopes is motivated by their connection to toric varieties. The thesis concerns the classification of smooth...

  17. Quantitative analysis of smooth muscle motion of aortic wall in different geometric configuration stage of left ventricle by tissue Doppler imaging in patients with essential hypertension%不同组织多普勒技术对高血压病左心室不同几何构型阶段主动脉壁平滑肌运动定量分析研究

    Institute of Scientific and Technical Information of China (English)

    高继康; 郑凤华; 袁华芳; 马芳花

    2013-01-01

    aortic wal motion in dif-ferent geometric configuration stage of left ventricle in patients with essential hypertension (EH). Methods The curves of tissue velocity imaging, tissue tracking imaging, strain imaging and strain rate imaging of aortic wal were obtained, and the peak sys-tolic velocity of aorta (AOPVs), peak systolic displacement of aorta (AOPDs), peak systolic strain of aorta (AOPSs), peak systolic strain rate of aorta (AOPSRs) , early diastolic velocity of aorta (AOVe), atrial systolic velocity of aorta (AOVa), early diastolic strain rate of aorta (AOEsr) and atrial systolic strain rate of aorta (AOAsr) were measured in each curves. The AOVe/AOVa and AOEsr/AOAsr were calculated. Results There were statistical differences in the mean AOPSs, AOVe, AOVa, AOEsr and AOEsr/Asr between control group (CG) and the left ventricular normal geometry group (LV-NGG), left ventricular concentric re-modeling group (LV-CRG), left ventricular concentric hypertrophy group (LV-CHG) , left ventricular eccentric hypertrophy group (LV-EHG); in the mean AOPDs between the CG and the LV-CRG, LV-CHG, LV-EHG; in the mean AOVe/Va between the CG and the LV-NGG , LV-CRG, LV-CHG f (P<0.05). There were statistical differences in the mean AOPVs and AOPDs between the LV-NGG and CG, LV-CRG, LV-CHG, LV-EHG (P<0.05). There were statistical differences in the mean AOPVs between the LV-CRG and CG, LV-CHG, LV-EHG;in the mean AOPSs between the LV-CRG and LV-NGG, LV-CHG, LV-EHG (P<0.05). There were statistical differences in the mean AOPVs between the LV-CRG and the CG, LV-CHG, LV-EHG(P<0.05). There were statistical differences in the mean AOAsr and AOVe/Va between the LV-EHG and the CG, LV-NGG, LV-CRG LV-CHG(P<0.05). There were statistical differences in the mean AOPSRs between the LV-NGG, LV-EHG and the CG, LV-CRG, LV-CHG;in the mean AOEsr/Asr between the LV-NGG, LV-CRG and the LV-EHG, LV-CHG (P<0.05). Conclusion The motions and the smooth muscle function of aortic wal s in different geometric

  18. Ultrastructure of Reissner's membrane in the rabbit

    DEFF Research Database (Denmark)

    Qvortrup, K.; Rostgaard, Jørgen; Bretlau, P.

    1994-01-01

    Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit......Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit...

  19. Diabetic conditions promote binding of monocytes to vascular smooth muscle cells and their subsequent differentiation

    OpenAIRE

    Meng, Li; Park, Jehyun; Cai, Qiangjun; Lanting, Linda; Reddy, Marpadga A; Natarajan, Rama

    2009-01-01

    Diabetes is associated with significantly accelerated rates of atherosclerosis, key features of which include the presence of excessive macrophage-derived foam cells in the subendothelial space. We examined the hypothesis that enhanced monocyte-vascular smooth muscle cell (VSMC) interactions leading to subendothelial monocyte retention and differentiation to macrophages under diabetic conditions may be underlying mechanisms. Human aortic VSMCs (HVSMCs) treated with diabetic stimuli high gluco...

  20. Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms.

    Directory of Open Access Journals (Sweden)

    Batmunkh Bumdelger

    Full Text Available 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.

  1. Study of Laser Scanning Confocal Microscope in Penis Corpus Cavernsum Smooth Muscle Cell in Rabbits%应用激光扫描共聚焦显微镜对家兔阴茎海绵体平滑肌细胞的研究

    Institute of Scientific and Technical Information of China (English)

    陈智; 刘继红

    2002-01-01

    Objective To study the changes in intracellular calcium concentration ( [ Ca2 + i] ) of penis corpus cavernsumsmooth muscle cell(PCSMC) in rabbits and to establish experimental model of detecting intracellular calcium. Methods Byusing laser scanning confocal microscope (LSCM), we investigated the [ Ca2 + i fluorescence signals change in cultured PCSMCin vitro. Results In this case, the loading effect is significant when PCSMCs are loaded with 5μmol/L Fluo- 3/AM(PH = 7.4) in 37℃. Cytoplasmic free calcium is well - distributed in integral cell. Base fluorescent intensity in different cytoplasm isdistinct. Conclusion To mark cytoplasmic free calcium needs suitable condition. Creation of the model offers good method tostudy the effect of different medicine in PCSMC.

  2. Double prosthetic aortic valve. Case report.

    Science.gov (United States)

    Liddicoat, J E; Bekassy, S M; De Bakey, M E

    1975-05-01

    A 55-year-old man underwent insection of a Hufnagel valve into his descending thoracic aorta for aortic valve insufficiency 18 years ago. He remained asymptomatic for 16 years. Because of progressive left ventricular failure his incompetent aortic valve was replaced with a De Bakey carbon ball aortic valve prosthesis 2 years later. Currently, 21 months after the operation, he is doing well with two aortic valves. Review of the literature suggests that he is the first patient reported with two aortic valves functioning concomitantly and one of the longest surviving patients with a Hufnagel valve.

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

    Science.gov (United States)

    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.

  4. Transfemoral transcatheter aortic valve implantation in a patient with a severe aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump support.

    Science.gov (United States)

    Chodór, Piotr; Wilczek, Krzysztof; Przybylski, Roman; Świątkowski, Andrzej; Głowacki, Jan; Kalarus, Zbigniew; Zembala, Marian

    2015-01-01

    The following paper presents a patient with severe aortic stenosis and severely reduced left ventricular ejection fraction with intra-aortic balloon pump counterpulsation support, who underwent transfemoral aortic valve implantation of a CoreValve prosthesis.

  5. Transfemoral transcatheter aortic valve implantation in a patient with a severe aortic stenosis and cardiogenic shock requiring intra-aortic balloon pump support

    OpenAIRE

    Chodór, Piotr; Wilczek, Krzysztof; Przybylski, Roman; Świątkowski, Andrzej; Głowacki, Jan; Kalarus, Zbigniew; Zembala, Marian

    2015-01-01

    The following paper presents a patient with severe aortic stenosis and severely reduced left ventricular ejection fraction with intra-aortic balloon pump counterpulsation support, who underwent transfemoral aortic valve implantation of a CoreValve prosthesis.

  6. Aortic Root Enlargement or Sutureless Valve Implantation?

    Directory of Open Access Journals (Sweden)

    Nikolaos G. Baikoussis

    2016-11-01

    Full Text Available Aortic valve replacement (AVR in patients with a small aortic annulus is a challenging issue. The importance of prosthesis–patient mismatch (PPM post aortic valve replacement (AVR is controversial but has to be avoided. Many studies support the fact that PPM has a negative impact on short and long term survival. In order to avoid PPM, aortic root enlargement may be performed. Alternatively and keeping in mind that often some comorbidities are present in old patients with small aortic root, the Perceval S suturelles valve implantation could be a perfect solution. The Perceval sutureless bioprosthesis provides reasonable hemodynamic performance avoiding the PPM and providing the maximum of aortic orifice area. We would like to see in the near future the role of the aortic root enlargement techniques in the era of surgical implantation of the sutureless valve (SAVR and the transcatheter valve implantation (TAVI.

  7. Genetic and Epigenetic Regulation of Aortic Aneurysms

    Science.gov (United States)

    Kim, Ha Won

    2017-01-01

    Aneurysms are characterized by structural deterioration of the vascular wall leading to progressive dilatation and, potentially, rupture of the aorta. While aortic aneurysms often remain clinically silent, the morbidity and mortality associated with aneurysm expansion and rupture are considerable. Over 13,000 deaths annually in the United States are attributable to aortic aneurysm rupture with less than 1 in 3 persons with aortic aneurysm rupture surviving to surgical intervention. Environmental and epidemiologic risk factors including smoking, male gender, hypertension, older age, dyslipidemia, atherosclerosis, and family history are highly associated with abdominal aortic aneurysms, while heritable genetic mutations are commonly associated with aneurysms of the thoracic aorta. Similar to other forms of cardiovascular disease, family history, genetic variation, and heritable mutations modify the risk of aortic aneurysm formation and provide mechanistic insight into the pathogenesis of human aortic aneurysms. This review will examine the relationship between heritable genetic and epigenetic influences on thoracic and abdominal aortic aneurysm formation and rupture. PMID:28116311

  8. Development of the human aortic arch system captured in an interactive three-dimensional reference model.

    Science.gov (United States)

    Rana, M Sameer; Sizarov, Aleksander; Christoffels, Vincent M; Moorman, Antoon F M

    2014-06-01

    Variations and mutations in the human genome, such as 22q11.2 microdeletion, can increase the risk for congenital defects, including aortic arch malformations. Animal models are increasingly expanding our molecular and genetic insights into aortic arch development. However, in order to justify animal-to-human extrapolations, a human morphological, and molecular reference model would be of great value, but is currently lacking. Here, we present interactive three-dimensional reconstructions of the developing human aortic arch system, supplemented with the protein distribution of developmental markers for patterning and growth, including T-box transcription factor TBX1, a major candidate for the phenotypes found in patients with the 22q11.2 microdeletion. These reconstructions and expression data facilitate unbiased interpretations, and reveal previously unappreciated aspects of human aortic arch development. Based on our reconstructions and on reported congenital anomalies of the pulmonary trunk and tributaries, we postulate that the pulmonary arteries originate from the aortic sac, rather than from the sixth pharyngeal arch arteries. Similar to mouse, TBX1 is expressed in pharyngeal mesenchyme and epithelia. The endothelium of the pharyngeal arch arteries is largely negative for TBX1 and family member TBX2 but expresses neural crest marker AP2α, which gradually decreases with ongoing development of vascular smooth muscle. At early stages, the pharyngeal arch arteries, aortic sac, and the dorsal aortae in particular were largely negative for proliferation marker Ki67, potentially an important parameter during aortic arch system remodeling. Together, our data support current animal-to-human extrapolations and future genetic and molecular analyses using animal models of congenital heart disease. © 2013 Wiley Periodicals, Inc.

  9. Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

    Science.gov (United States)

    Ma, Xiucui; Tittiger, Mindy; Knutsen, Russell H.; Kovacs, Attila; Schaller, Laura; Mecham, Robert P.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to α-l-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice. MPS I mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders. PMID:18479957

  10. Pasteur effect in vascular and intestinal smooth muscle.

    Science.gov (United States)

    Pettersson, G; Lundholm, L

    1985-01-01

    The increase in lactate production on changing from aerobic to anaerobic conditions, i.e. the Pasteur effect, has been reported to be small in vascular muscle and especially in aorta. It has been suggested that this may be an artefact caused by damage to the intimal endothelium. We have compared the Pasteur effect in different kinds of pig arteries, but also in rabbit colon. The aerobic lactate production in 60 min was 11-15 mumol/g in the aorta and the carotid artery, but 3 mumol/g in the mesenteric and renal arteries and 4 mumol/g in the rabbit colon. The increase in lactate production under anaerobic conditions was 12-20 mumol/g/60 min in the carotid artery, aorta and rabbit colon and 10 mumol/g/60 min in the mesenteric and renal arteries. When calculated in per cent, the Pasteur effect was greater in the mesenteric artery than in the aorta, but the actual rise in lactate production in mumol/g was higher in the aorta and carotid artery. The high aerobic lactate production of smooth muscle in vitro may be related to its low ability to oxidize glucose; some other substrates may be preferentially oxidized when present in vitro or in vivo.

  11. Remodelling of the aortic root in severe tricuspid aortic stenosis: implications for transcatheter aortic valve implantation

    Energy Technology Data Exchange (ETDEWEB)

    Stolzmann, Paul; Desbiolles, Lotus; Scheffel, Hans; Leschka, Sebastian; Marincek, Borut; Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic Radiology, Zurich (Switzerland); Knight, Joseph; Kurtcuoglu, Vartan; Poulikakos, Dimos [Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich (Switzerland); Maier, Willibald [University Hospital Zurich, Cardiovascular Center, Zurich (Switzerland); Plass, Andre [University Hospital Zurich, Clinic for Cardiovascular Surgery, Zurich (Switzerland)

    2009-06-15

    Detailed knowledge of aortic root geometry is a prerequisite to anticipate complications of transcatheter aortic valve (TAV) implantation. We determined coronary ostial locations and aortic root dimensions in patients with aortic stenosis (AS) and compared these values with normal subjects using computed tomography (CT). One hundred consecutive patients with severe tricuspid AS and 100 consecutive patients without valvular pathology (referred to as the controls) undergoing cardiac dual-source CT were included. Distances from the aortic annulus (AA) to the left coronary ostium (LCO), right coronary ostium (RCO), the height of the left coronary sinus (HLS), right coronary sinus (HRS), and aortic root dimensions [diameters of AA, sinus of Valsalva (SV), and sino-tubular junction(STJ)] were measured. LCO and RCO were 14.9 {+-} 3.2 mm (8.2-25.9) and 16.8 {+-} 3.6 mm (12.0-25.7) in the controls, 15.5 {+-} 2.9 mm (8.8-24.3) and 17.3 {+-} 3.6 mm (7.3-26.0) in patients with AS. Controls and patients with AS had similar values for LCO (P = 0.18), RCO (P = 0.33) and HLS (P = 0.88), whereas HRS (P < 0.05) was significantly larger in patients with AS. AA (r = 0.55,P < 0.001), SV (r = 0.54,P < 0.001), and STJ (r = 0.52,P < 0.001) significantly correlated with the body surface area in the controls; whereas no correlation was found in patients with AS. Patients with AS had significantly larger AA (P < 0.01) and STJ (P < 0.01) diameters when compared with the controls. In patients with severe tricuspid AS, coronary ostial locations were similar to the controls, but a transverse remodelling of the aortic root was recognized. Owing to the large distribution of ostial locations and the dilatation of the aortic root, CT is recommended before TAV implantation in each patient. (orig.)

  12. The Year of the Rabbit

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Every year of the Chinese lunar calendar corresponds with an animal. The rat,ox, tiger, rabbit, dragon, snake, horse,sheep, monkey, rooster, dog and pig make up the Chinese zodiac, which repeats in a12-year cycle. This year’s Chinese NewYear rings in the Year of the Rabbit.

  13. Welfare assessment in pet rabbits

    NARCIS (Netherlands)

    Schepers, F.; Koene, P.; Beerda, B.

    2009-01-01

    One million pet rabbits are kept in The Netherlands, but there are no data available on their behaviour and welfare. This study seeks to assess the welfare of pet rabbits in Dutch households and is a first step in the development of a welfare assessment system. In an internet survey, housing

  14. Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br; Ozaki, Michiko Regina [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2014-07-15

    Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16{sup th} day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

  15. Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Eros Antonio de Almeida

    2014-07-01

    Full Text Available Background: Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective: To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods: Thirty rabbits divided into six groups (n = 5: G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg; G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg; G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg; G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg. After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK, aspartate aminotransferase (AST, alanine aminotransferase (ALT were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results: Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion: Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

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

    Science.gov (United States)

    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

  17. INFECTIOUS MYXOMATOSIS OF RABBITS

    Science.gov (United States)

    Rivers, T. M.

    1930-01-01

    The virus of infectious myxomatosis of rabbits (Sanarelli) induces multiple lesions in the skin, lymph glands, tunica vaginalis,epididymis, testicle, spleen, and lungs. Growth and destruction of cells in the epidermis overlying the myxomatous masses leads to the formation of vesicles. Cytoplasmic inclusions are found in affected epidermal cells. Occasionally, similar inclusions are seen in other involved epithelial cells. The nature of the inclusions is an open question. In the myxomatous masses situated in the subcutaneous and other tissues, evidences of alteration and growth of certain cells are observed. PMID:19869741

  18. The White Rabbit project

    CERN Document Server

    Serrano, J; Gousiou, E; van der Bij, E; Wlostowski, T; Daniluk, G; Lipinski, M

    2013-01-01

    White Rabbit (WR) is a multi-laboratory, multi- company collaboration for the development of a new Ethernet-based technology which ensures sub-nanosecond synchronisation and deterministic data transfer. The project uses an open source paradigm for the development of its hardware, gateware and software components. This article provides an introduction to the technical choices and an explanation of the basic principles underlying WR. It then describes some possible applications and the current status of the project. Finally, it provides insight on current developments and future plans.

  19. Statins for aortic valve stenosis

    Directory of Open Access Journals (Sweden)

    Luciana Thiago

    Full Text Available ABSTRACT BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. Selection criteria: Randomized controlled clinical trials (RCTs comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity, freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants with placebo (1175 participants. We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD -0.54, 95% confidence interval (CI -1.88 to 0.80; participants = 1935; studies = 2, valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2

  20. Transcatheter valve-in-valve implantation due to severe aortic regurgitation in a degenerated aortic homograft

    DEFF Research Database (Denmark)

    Olsen, Lene Kjaer; Engstrøm, Thomas; Søndergaard, Lars

    2009-01-01

    Transcatheter aortic valve implantation (TAVI) in severe aortic stenosis has proven to be a feasible and effective treatment modality for inoperable patients. Until now, neither aortic regurgitation nor degenerated bioprostheses has been an indication for TAVI. However, this article reports...... a successful valve-in-valve implantation of a CoreValve aortic valve prosthesis through the right subclavian artery in a case of severe aortic regurgitation within a degenerated aortic homograft. The case exemplifies the possibilities of expanding the indications for TAVI, as well as other vascular access...

  1. Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits

    Directory of Open Access Journals (Sweden)

    Raj Santhana

    2010-04-01

    Full Text Available Abstract Background Piper sarmentosum (P.s has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically. Aim The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits. Methods Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol, W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg, W2 - 1% cholesterol with water extract of P.s (125 mg/kg, W3 - 1% cholesterol with water extract of P.s (250 mg/kg, W4 - 1% cholesterol with water extract of P.s (500 mg/kg and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg. All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study. Results Rabbits fed only with high cholesterol diet 1% cholesterol (CH showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg i.e. W4 group showed significant reduction (30 ± 6.0%, p Conclusion Administration of P.s extract has protective effect against atheroscleros

  2. Cilostazol inhibits accumulation of triglyceride in aorta and platelet aggregation in cholesterol-fed rabbits.

    Directory of Open Access Journals (Sweden)

    Hideki Ito

    Full Text Available Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities.

  3. Download this PDF file

    African Journals Online (AJOL)

    Dr Olaleye

    in [Mg2+]0 on vascular smooth muscles of rabbit aortic, carotid and femoral arteries. Methods: Contractile .... smooth muscle contraction by mobilizing intracellular calcium pools as well as .... transport of Mg2+ . Am. J Physiol Heart Cir Physiol.

  4. The Topological Effects of Smoothing.

    Science.gov (United States)

    Shafii, S; Dillard, S E; Hlawitschka, M; Hamann, B

    2012-01-01

    Scientific data sets generated by numerical simulations or experimental measurements often contain a substantial amount of noise. Smoothing the data removes noise but can have potentially drastic effects on the qualitative nature of the data, thereby influencing its characterization and visualization via topological analysis, for example. We propose a method to track topological changes throughout the smoothing process. As a preprocessing step, we oversmooth the data and collect a list of topological events, specifically the creation and destruction of extremal points. During rendering, it is possible to select the number of topological events by interactively manipulating a merging parameter. The result that a specific amount of smoothing has on the topology of the data is illustrated using a topology-derived transfer function that relates region connectivity of the smoothed data to the original regions of the unsmoothed data. This approach enables visual as well as quantitative analysis of the topological effects of smoothing.

  5. Conservative smoothing versus artificial viscosity

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, C.; Hicks, D.L. [Michigan Technological Univ., Houghton, MI (United States); Swegle, J.W. [Sandia National Labs., Albuquerque, NM (United States). Solid and Structural Mechanics Dept.

    1994-08-01

    This report was stimulated by some recent investigations of S.P.H. (Smoothed Particle Hydrodynamics method). Solid dynamics computations with S.P.H. show symptoms of instabilities which are not eliminated by artificial viscosities. Both analysis and experiment indicate that conservative smoothing eliminates the instabilities in S.P.H. computations which artificial viscosities cannot. Questions were raised as to whether conservative smoothing might smear solutions more than artificial viscosity. Conservative smoothing, properly used, can produce more accurate solutions than the von Neumann-Richtmyer-Landshoff artificial viscosity which has been the standard for many years. The authors illustrate this using the vNR scheme on a test problem with known exact solution involving a shock collision in an ideal gas. They show that the norms of the errors with conservative smoothing are significantly smaller than the norms of the errors with artificial viscosity.

  6. Smoothness in Binomial Edge Ideals

    Directory of Open Access Journals (Sweden)

    Hamid Damadi

    2016-06-01

    Full Text Available In this paper we study some geometric properties of the algebraic set associated to the binomial edge ideal of a graph. We study the singularity and smoothness of the algebraic set associated to the binomial edge ideal of a graph. Some of these algebraic sets are irreducible and some of them are reducible. If every irreducible component of the algebraic set is smooth we call the graph an edge smooth graph, otherwise it is called an edge singular graph. We show that complete graphs are edge smooth and introduce two conditions such that the graph G is edge singular if and only if it satisfies these conditions. Then, it is shown that cycles and most of trees are edge singular. In addition, it is proved that complete bipartite graphs are edge smooth.

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

    Science.gov (United States)

    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. Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity.

    Science.gov (United States)

    Atkins, Kevin B; Seki, Yoshinori; Saha, Jharna; Eichinger, Felix; Charron, Maureen J; Brosius, Frank C

    2015-02-01

    Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth-muscle-specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild-type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F2α was significantly increased in endothelium-intact aortic rings from hypertensive wild-type mice but not in aortae of SMG4 mice. Inhibition of Rho-kinase equally reduced serotonin-stimulated contractility in aortae of hypertensive wild-type and SMG4-mice. In addition, acetylcholine-stimulated relaxation was significantly decreased in aortic rings of hypertensive wild-type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase-2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase-2 had no effect on relaxation in rings of hypertensive wild-type mice. Cyclooxygenase-2 protein expression was decreased in hypertensive wild-type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium-dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses.

  9. Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits.

    Science.gov (United States)

    Bremer, Yvonne A; Salloum, Fadi; Ockaili, Ramzi; Chou, Eric; Moskowitz, William B; Kukreja, Rakesh C

    2005-01-01

    Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p sildenafil group compared with controls (n = 6/group, p sildenafil-treated group had significant reduction in infarct size (15.5 +/- 1.2 versus 33 +/- 2.3 in the saline group, % risk area, mean +/- SEM, n = 10-15/group, p sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size.

  10. Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: a meta analysis

    Institute of Scientific and Technical Information of China (English)

    WU Yi-cheng; ZHANG Jian-feng; SHEN Wei-feng; ZHAO Qiang

    2013-01-01

    Background Transcatheter aortic valve implantation (TAVI) has emerged as the treatment choice for non-operable patients with severe symptomatic aortic stenosis (AS) and may be a good alternative to surgery for those at very high or prohibitive surgical risk.We performed a meta-analysis to evaluate the comparative benefits of TAVI versus surgical aortic valve replacement (SAVR) in patients with severe AS.Methods A comprehensive literature search of PubMed,Embase,ScienceDirect and Cochrane Central Register of Controlled trials was performed,and randomized trials as well as cohort studies with propensity score analysis were included.Results One randomized trial (n=699) and six retrospective cohort studies (n=781) were selected for meta-analysis.Mortality at 30-day and 1-year follow-up was comparable between TAVI and SAVR.Despite similar incidences of stroke,myocardial infarction,re-operation for bleeding,and renal failure requiring dialysis,TAVI was associated with a lower occurrence rate of new-onset atrial fibrillation (OR 0.51,95% CI 0.33-0.78) and shorter procedural time (mean difference -67.50 minutes,95% CI-87.20 to-47.81 minutes).Post-operative aortic regurgitation and permanent pacemaker implantation were more common in patients after TAVI than in those with SAVR (OR 5.53,95% CI 3.41-8.97; OR 1.71,95% Cl 1.02-2.84,respectively).Conclusion In patients with severe symptomatic AS,TAVI and SAVR did not differ with respect to short-and mid-term survival,but the incidence of permanent pacemaker implantation and post-procedural aortic regurgitation remain relatively high after TAVI.

  11. A three-dimensional theoretical model of the relationship between cavernosal expandability and percent cavernosal smooth muscle.

    Science.gov (United States)

    Luo, Haibiao; Goldstein, Irwin; Udelson, Daniel

    2007-05-01

    Percent corporal smooth muscle content, a traditional predictor of corporal veno-occlusive function, is invasive and clinically assessed by histomorphometric analyses of erectile tissue biopsies. Cavernosal "expandability" which may be a more physiologically relevant parameter is a measure of work performed to achieve penile erection, and as a consequence, an indicator of the ability to approach maximum penile volume at low intracavernosal pressure. To demonstrate that cavernosal "expandability" determined by noninvasive methodology can replace the determination of percent smooth muscle. To predict Young's modulus for the corpora cavernosa in rabbits and, this by inference, in humans; the latter facilitates the comparison of resistance to penile expansion presented by the tunica vs. cavernosal tissue. A refined three-dimensional formula for cavernosal expandability, defined as the negative reciprocal of the cavernosal bulk modulus in the semierect state, was derived as a function of percent corporal smooth muscle content, using principles of engineering mechanics of materials. The model included Young's modulus, E, for the corpora cavernosa as an unknown parameter. Volume-pressure data obtained from three groups of New Zealand white rabbits: (i) control group (N = 7); (ii) hypercholesterolemic group (N = 5) on 0.5%; (iii) atherosclerotic group (N = 8), was plotted, and compared with the model. Data points of mean cavernosal expandability (0.012-0.017 (mm Hg)(-1)) vs. percent trabecular smooth muscle content (33.9-45.4%) for the three groups of rabbits were analyzed. The revised model formula was fitted to the existing rabbit experimental data points producing a value of Young's modulus equal to 0.01 (MPa). Rabbit cavernosal expandability can predict percent smooth muscle content. Cavernosal Young's modulus can be predicted. Further clinical research efforts to provide human data are needed.

  12. [Surgical technique of aortic valve replacement for small aortic annulus in elderly patients].

    Science.gov (United States)

    Hata, T; Fujiwara, K; Furukawa, H; Tsushima, Y; Yoshitaka, H; Kuinose, M; Minami, H; Ishida, A; Tamura, K; Totsugawa, T; Kanemitsu, H; Ozawa, M

    2006-04-01

    Recent reports have shown that aortic valve replacement in elderly patients over 65 years with atherosclerotic aortic stenosis and a small aortic annulus is possible by using a small sized bioprosthesis (Carpentier-Edwards pericardial valve). Here we present out surgical technique. Firstly, the native calcified aortic valve was removed completely to gain total exposure of the surrounding aortic root and sinus of Valsalva like Bentall procedure. Secondly, a small sized bioprosthesis was implanted with intermittent noneverting mattress 2-0 sutures with spaghetti and small polytetrafluoroethylene (PTFE) felt. Aortic annulus is the dilated by inserting Hegar dilator sizing from 25 to 27 mm. Therefore, aortic valve replacement for small aortic annulus in intra- or supra-annular position should be easily accomplished. Good surgical results and hemodynamic state were achieved in 25 consecutive cases using this technique.

  13. Smooth analysis in Banach spaces

    CERN Document Server

    Hájek, Petr

    2014-01-01

    This bookis aboutthe subject of higher smoothness in separable real Banach spaces.It brings together several angles of view on polynomials, both in finite and infinite setting.Also a rather thorough and systematic view of the more recent results, and the authors work is given. The book revolves around two main broad questions: What is the best smoothness of a given Banach space, and its structural consequences? How large is a supply of smooth functions in the sense of approximating continuous functions in the uniform topology, i.e. how does the Stone-Weierstrass theorem generalize into in

  14. Oculoscopy in Rabbits and Rodents.

    Science.gov (United States)

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  15. Evaluation of arterial impairment after experimental gelatin sponge embolization in a rabbit renal model

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jung Suk; Lee, Hae Gi; Chun, Ho Jong; Choi, Byung Gil; Choi, Yeong Jin [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-02-15

    Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle actin immunohistochemical stained sections. Gelatin sponge particles were mainly observed in the segmental and interlobar arteries. Transmural inflammation of the embolized arterial wall and mild thickening of the media were observed 1 week after embolization. Resorption of the gelatin sponge and organization of thrombus accompanied by foreign body reactions, were observed from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group showed vessel lumens filled mostly with organized thrombi, resulting in severe stenosis. Additionally, vessels showed a thickened intima that contained migrating smooth muscle cells and accompanying interruption of the internal elastic lamina. The migrating smooth muscle cells were distributed around the recanalized arterial lumen. Gelatin sponge embolization may induce arterial stenosis by causing organized thrombus and intimal hyperplasia, which consists of migrating smooth muscle cells and intimal collagen deposits.

  16. Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis

    DEFF Research Database (Denmark)

    Jander, Nikolaus; Gohlke-Bärwolf, Christa; Bahlmann, Edda

    2014-01-01

    To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are......To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are...

  17. Aortic endograft sizing in trauma patients with hemodynamic instability

    NARCIS (Netherlands)

    Jonker, Frederik H. W.; Verhagen, Hence J. M.; Mojibian, Hamid; Davis, Kimberly A.; Moll, Frans L.; Muhs, Bart E.

    2010-01-01

    Objectives: To investigate changes in aortic diameter in hemodynamically unstable trauma patients and the implications for sizing of thoracic endovascular aortic repair (TEVAR) in patients with traumatic thoracic aortic injury (TTAI). Methods: We retrospectively evaluated all trauma patients that we

  18. Preliminary Evidence for Aortopathy and an X-Linked Parent-of-Origin Effect on Aortic Valve Malformation in a Mouse Model of Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Robert B. Hinton

    2015-07-01

    Full Text Available Turner syndrome (TS, most frequently caused by X-monosomy (45,X, is characterized in part by cardiovascular abnormalities, including aortopathy and bicuspid aortic valve (BAV. There is a need for animal models that recapitulate the cardiovascular manifestations of TS. Extracellular matrix (ECM organization and morphometrics of the aortic valve and proximal aorta were examined in adult 39,XO mice (where the parental origin of the single X was paternal (39,XPO or maternal (39,XMO and 40,XX controls. Aortic valve morphology was normal (tricuspid in all of the 39,XPO and 40,XX mice studied, but abnormal (bicuspid or quadricuspid in 15% of 39,XMO mice. Smooth muscle cell orientation in the ascending aorta was abnormal in all 39,XPO and 39,XMO mice examined, but smooth muscle actin was decreased in 39,XMO mice only. Aortic dilation was present with reduced penetrance in 39,XO mice. The 39,XO mouse demonstrates aortopathy and an X-linked parent-of-origin effect on aortic valve malformation, and the candidate gene FAM9B is polymorphically expressed in control and diseased human aortic valves. The 39,XO mouse model may be valuable for examining the mechanisms underlying the cardiovascular findings in TS, and suggest there are important genetic modifiers on the X chromosome that modulate risk for nonsyndromic BAV and aortopathy.

  19. Aortic root vasculitis associated with Cogan's syndrome.

    Science.gov (United States)

    Gasparovic, Hrvoje; Djuric, Zeljko; Bosnic, Dubravka; Petricevic, Mate; Brida, Margita; Dotlic, Snjezana; Biocina, Bojan

    2011-07-01

    Cogan's syndrome is characterized by nonsyphilitic interstitial keratitis and an audiovestibular disorder resembling Meniere disease. We report a patient with progressive congestive heart failure due to massive aortic and mitral insufficiency coupled with aortitis leading to an ascending aortic aneurysm. The patient underwent successful aortic root replacement and mitral valve repair. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Aortic valvuloplasty of calcific aortic stenosis with monofoil and trefoil balloon catheters: practical considerations

    NARCIS (Netherlands)

    S. Plante (Sylvain); M.J.B.M. van den Brand (Marcel); L.C.P. van Veen; C. di Mario (Carlo); C.E. Essed; K.J. Beatt (Kevin); P.W.J.C. Serruys (Patrick)

    1990-01-01

    textabstractIn order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic stenosis of various morphology. The degree of obstruction of the aortic orifice was ass

  1. The Efficacy of Autologous Femoropopliteal Vein Reconstruction for Primary Aortic and Aortic Graft Infection

    NARCIS (Netherlands)

    Dirven, M.; Jagt, M.F.P. van der; Barendregt, W.B.; Vliet, D. van der

    2015-01-01

    BACKGROUND: The objective of our study was to analyze the efficacy of autologous superficial femoropopliteal vein reconstruction for primary aortic or aortic graft infection. METHODS: We performed a retrospective analysis of 14 patients treated for an infected aortic prosthesis or primary infected a

  2. Transcatheter aortic valve replacement for bicuspid aortic stenosis 13years post heart transplant.

    Science.gov (United States)

    Julien, Maureen B; Desai, Nimesh; Brozena, Susan; Herrmann, Howard C

    2016-12-16

    Despite the widespread use of transcatheter aortic valve replacement (TAVR) for moderate and high-risk patients with severe aortic stenosis, it is utilized less frequently in patients with bicuspid aortic valves (BAV). Orthotopic heart transplant (OHT) donors tend to be younger and may have undiagnosed BAV. We present a case of successful TAVR in a patient with BAV thirteen years after OHT.

  3. New-onset atrial fibrillation after surgical aortic valve replacement and transcatheter aortic valve implantation

    DEFF Research Database (Denmark)

    Jørgensen, Troels Højsgaard; Thygesen, Julie Bjerre; Thyregod, Hans Gustav;

    2015-01-01

    Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic valve implantation (TAVI) have been shown to be the only treatments that can improve the natural cause of severe aortic valve stenosis. However, after SAVR and TAVI, the incidence of new-onset atrial fibrillation...

  4. New-Onset Atrial Fibrillation After Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Implantation

    DEFF Research Database (Denmark)

    Jørgensen, Troels Højsgaard; Thygesen, Julie Bjerre; Thyregod, Hans Gustav;

    2015-01-01

    Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic valve implantation (TAVI) have been shown to be the only treatments that can improve the natural cause of severe aortic valve stenosis. However, after SAVR and TAVI, the incidence of new-onset atrial fibrillation...

  5. New-Onset Atrial Fibrillation After Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Implantation

    DEFF Research Database (Denmark)

    Jørgensen, Troels Højsgaard; Thygesen, Julie Bjerre; Thyregod, Hans Gustav

    2015-01-01

    Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic valve implantation (TAVI) have been shown to be the only treatments that can improve the natural cause of severe aortic valve stenosis. However, after SAVR and TAVI, the incidence of new-onset atrial fibrillation...

  6. SMOOTHING BY CONVEX QUADRATIC PROGRAMMING

    Institute of Scientific and Technical Information of China (English)

    Bing-sheng He; Yu-mei Wang

    2005-01-01

    In this paper, we study the relaxed smoothing problems with general closed convex constraints. It is pointed out that such problems can be converted to a convex quadratic minimization problem for which there are good programs in software libraries.

  7. Low-gradient aortic stenosis.

    Science.gov (United States)

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

    2016-09-07

    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.

  8. Dietary supplementation with an extract of lycopene-rich tomatoes does not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Frederiksen, H.; Rasmussen, S.E.; Schrøder, Malene;

    2007-01-01

    Tomatoes are rich in lycopene and other carotenoids which have shown beneficial effects on CVD in epidemiological and intervention studies. In the present study the effect of an extract of lycopene-rich tomatoes, Lyc-O-Mato (R) on atherosclerosis was studied in Watanabe Heritable Hyperlipidemic...... rabbits. The rabbits were fed a control diet, a control diet supplemented with the tomato extract or a control diet supplemented with a mixture of plant oils for 16 weeks. Lycopene was detected only in plasma of rabbits receiving tomato extract. The tomato extract had no effect on cholesterol...... and triacylglycerol levels measured in total plasma, lipoprotein fractions and on aortic atherosclerosis evaluated biochemically and by microscopy. Oxidation of lipids in unfractionated plasma also was unaffected by the intake of tomato extract. In conclusion, the tomato extract increased plasma levels of lycopene...

  9. Wetting on smooth micropatterned defects

    OpenAIRE

    Debuisson, Damien; Dufour, Renaud; Senez, Vincent; Arscott, Steve

    2011-01-01

    We develop a model which predicts the contact angle hysteresis introduced by smooth micropatterned defects. The defects are modeled by a smooth function and the contact angle hysteresis is explained using a tangent line solution. When the liquid micro-meniscus touches both sides of the defect simultaneously, depinning of the contact line occurs. The defects are fabricated using a photoresist and experimental results confirm the model. An important point is that the model is scale-independent,...

  10. Aortic dilatation in children with systemic hypertension.

    Science.gov (United States)

    Gupta-Malhotra, Monesha; Devereux, Richard B; Dave, Archana; Bell, Cynthia; Portman, Ronald; Milewicz, Diana

    2014-04-01

    The aim of the study was to determine the presence of aortic dilatation in hypertensive children, the prevalence of which is 4% to 10% in hypertensive adults. Prospectively enrolled multiethnic children, untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at three levels: the sinus of Valsalva, supra-tubular junction, and the ascending aorta. Aortic dilatation was determined by z-score >2 at any one of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Among 142 consecutive hypertensive children (median age, 14 years; 45% females) aortic dilatation was detected in 2.8% (95% confidence interval, 1%-7%; median age, 16 years; 100% females). Children with aortic dilatation, when compared with those without, had significantly more aortic valve insufficiency (P = .005) and left ventricular hypertrophy (P = .018). Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation.

  11. Hybrid treatment of penetrating aortic ulcer

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Juan Antonio Herrero; Martins-Romeo, Daniela de Araujo; Escudero, Carlos Caparros; Falcon, Maria del Carmen Prieto; Batista, Vinicius Bianchi, E-mail: jaherrero5@hotmail.com [Unidade de Gestao Clinica (UGC) de Diagnostico por Imagem - Hosppital Universitario Virgen Macarena, Sevilha (Spain); Vazquez, Rosa Maria Lepe [Unit of Radiodiagnosis - Hospital Nuestra Senora de la Merced, Osuna, Sevilha (Spain)

    2015-05-15

    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. (author)

  12. [Surgery of aortic dissection: for which patient?].

    Science.gov (United States)

    Verhoye, Jean-Philippe; Abouliatim, Issam; Larralde, Antoine; Beneux, Xavier; Heautot, Jean-François

    2011-01-01

    In the acute stage (less than two weeks), surgery is indicated for Stanford type A aortic dissections. With respect to the initial work-up, surgery consists in replacing the ascending aorta, sometimes the aortic arch (with supra aortic vessels reimplantation), and aortic valve replacement (valve replacement, Bentall valved tube or valve sparing Tyron David technique). Ischemic visceral complications must be searched for and treated by endovascular techniques or surgery. Aneurismal evolution of chronic dissections must be treated surgically. Replacement can encompass the entire aorta. Copyright © 2010. Published by Elsevier Masson SAS.

  13. Aortic dissection: magnetic resonance imaging.

    Science.gov (United States)

    Amparo, E G; Higgins, C B; Hricak, H; Sollitto, R

    1985-05-01

    Fifteen patients with suspected or known aortic dissection were imaged with magnetic resonance (MR). Thirteen of these patients were eventually shown to have dissection. In most instances the diagnosis was established by aortography and/or computed tomography (CT) prior to the MR study. Surgical proof (6/13) and/or aortographic proof (10/13) were available in 11/13 patients with aortic dissection. MR demonstrated the intimal flap and determined whether the dissection was type A or type B. In addition, MR: differentiated between the true and false lumens; determined the origins of the celiac, superior mesenteric, and renal arteries from the true or false lumen in the cases where the dissection extended into the abdominal aorta (8/12); allowed post-surgical surveillance of the dissection; and identified aortoannular ectasia in the three patients who had Marfan syndrome. In addition to the 13 cases with dissection, there were two cases in whom the diagnosis of dissection was excluded by MR. Our early experience suggests that MR can serve as the initial imaging test in clinically suspected cases of aortic dissection and that the information provided by MR is sufficient to manage many cases. Additionally, MR obviates the use of iodinated contrast media.

  14. Exotic smoothness and quantum gravity

    Energy Technology Data Exchange (ETDEWEB)

    Asselmeyer-Maluga, T, E-mail: torsten.asselmeyer-maluga@dlr.d [German Aerospace Center, Berlin, Germany and Loyola University, New Orleans, LA (United States)

    2010-08-21

    Since the first work on exotic smoothness in physics, it was folklore to assume a direct influence of exotic smoothness to quantum gravity. Thus, the negative result of Duston (2009 arXiv:0911.4068) was a surprise. A closer look into the semi-classical approach uncovered the implicit assumption of a close connection between geometry and smoothness structure. But both structures, geometry and smoothness, are independent of each other. In this paper we calculate the 'smoothness structure' part of the path integral in quantum gravity assuming that the 'sum over geometries' is already given. For that purpose we use the knot surgery of Fintushel and Stern applied to the class E(n) of elliptic surfaces. We mainly focus our attention to the K3 surfaces E(2). Then we assume that every exotic smoothness structure of the K3 surface can be generated by knot or link surgery in the manner of Fintushel and Stern. The results are applied to the calculation of expectation values. Here we discuss the two observables, volume and Wilson loop, for the construction of an exotic 4-manifold using the knot 5{sub 2} and the Whitehead link Wh. By using Mostow rigidity, we obtain a topological contribution to the expectation value of the volume. Furthermore, we obtain a justification of area quantization.

  15. Exotic Smoothness and Quantum Gravity

    CERN Document Server

    Asselmeyer-Maluga, Torsten

    2010-01-01

    Since the first work on exotic smoothness in physics, it was folklore to assume a direct influence of exotic smoothness to quantum gravity. Thus, the negative result of Duston (arXiv:0911.4068) was a surprise. A closer look into the semi-classical approach uncovered the implicit assumption of a close connection between geometry and smoothness structure. But both structures, geometry and smoothness, are independent of each other. In this paper we calculate the "smoothness structure" part of the path integral in quantum gravity assuming that the "sum over geometries" is already given. For that purpose we use the knot surgery of Fintushel and Stern applied to the class E(n) of elliptic surfaces. We mainly focus our attention to the K3 surfaces E(2). Then we assume that every exotic smoothness structure of the K3 surface can be generated by knot or link surgery a la Fintushel and Stern. The results are applied to the calculation of expectation values. Here we discuss the two observables, volume and Wilson loop, f...

  16. The cottontail rabbits of Virginia

    Science.gov (United States)

    Llewellyn, L.M.; Handley, C.O.

    1945-01-01

    Five races of cottontail rabbits belonging to three species occur in Virginia. One of them, the Mearns cottontail (Sylvilagus floridanus mearnsi), is reported here for the first time. It occurs in six southwestern counties of the state, while the eastern cottontail (S. f. mallurus) occurs in the remainder of the state with the exception of Smith and Fishermans islands off the eastern coast of Cape Charles, where it is replaced by Hitchens cottontail (S. f. hitchensi). The New England cottontail (S. transitionalis) is found on the higher mountain peaks, above 3000 feet, and the swamp rabbit (S. palustris) occurs in the Dismal Swamp region of southeastern Virginia.....The height of the breeding season for the eastern cottontail in Virginia is March and April, but breeding continues through the entire year except in December and January. The average litter size based on embryo counts was 4.7. The sex ratio of 234 specimens from all parts of the state, taken mostly in the December to February period, was 53 males to 47 females. That of a group of 145 rabbits live-trapped at Blacksburg during February and Marchwas 58 males to 42 females. The figures show that males are more active than females during the winter months, and therefore are more easily taken then....In transplanting cottontails from one section of the state to another, it is recommended that only cottontails of the same race as those originally present in the region being restocked be released there....Tularemia is not a common disease among rabbits in Virginia, but the rabbit ticks are often carriers of the disease and may transmit it to rabbits. Rabbit ticks are also found to be carriers of Rocky Mountain fever and American Q. fever. After the ticks drop off the rabbits to hibernate in the ground, which is likely to occur during mid-winter in Virginia, there is relatively little danger of humans contracting tularemia by contact with rabbits. Present laws in Virginia which prohibit rabbit hunting until the

  17. A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis

    DEFF Research Database (Denmark)

    Nielsen, Hans Henrik Møller; Klaaborg, Kaj E; Nissen, Henrik

    2012-01-01

    In a prospective randomised trial we aimed to compare transapical transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve replacement (SAVR) in operable elderly patients.......In a prospective randomised trial we aimed to compare transapical transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve replacement (SAVR) in operable elderly patients....

  18. Possible dual role of decorin in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Koshiro Ueda

    Full Text Available 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.

  19. Smooth quantum gravity: Exotic smoothness and Quantum gravity

    CERN Document Server

    Asselmeyer-Maluga, Torsten

    2016-01-01

    Over the last two decades, many unexpected relations between exotic smoothness, e.g. exotic $\\mathbb{R}^{4}$, and quantum field theory were found. Some of these relations are rooted in a relation to superstring theory and quantum gravity. Therefore one would expect that exotic smoothness is directly related to the quantization of general relativity. In this article we will support this conjecture and develop a new approach to quantum gravity called \\emph{smooth quantum gravity} by using smooth 4-manifolds with an exotic smoothness structure. In particular we discuss the appearance of a wildly embedded 3-manifold which we identify with a quantum state. Furthermore, we analyze this quantum state by using foliation theory and relate it to an element in an operator algebra. Then we describe a set of geometric, non-commutative operators, the skein algebra, which can be used to determine the geometry of a 3-manifold. This operator algebra can be understood as a deformation quantization of the classical Poisson alge...

  20. [Emergent transcatheter aortic valve implantation in a patient with bicuspid aortic valve stenosis in cardiogenic shock].

    Science.gov (United States)

    Pizzighini, S; Finet, G; Obadia, J-F; Revel, D; Bresson, D; Rioufol, G

    2015-02-01

    Transcatheter aortic valve implantation is a therapeutic option for high-risk patients with severe aortic valve stenosis and with cardiac symptoms. This procedure requires the preliminary evaluation by a "heart team" and presents some contraindications. We report the case of a 58-year-old man with severe bicuspid aortic valve stenosis and cardiogenic shock. In spite of contraindications and because of the failure of balloon aortic valvuloplasty, transcatheter aortic valve implantation was performed in emergency. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Aortic valve replacement with cryopreserved aortic allograft: ten-year experience.

    Science.gov (United States)

    Doty, J R; Salazar, J D; Liddicoat, J R; Flores, J H; Doty, D B

    1998-02-01

    Cryopreserved aortic allograft can be used for aortic valve replacement in congenital, rheumatic, degenerative, and infected native valve conditions, as well as failed prosthetic valves. This study was conducted to determine the long-term results of aortic valve replacement with cryopreserved aortic allografts. Aortic valve replacement with cryopreserved aortic allografts was performed in 117 patients from July 1985 until August 1996. All patients requiring aortic valve replacement regardless of valve disease were considered for allograft replacement; the valve was preferentially used in patients under age 55 years and in the setting of bacterial endocarditis. Four operative techniques involving cryopreserved aortic allografts were used: freehand aortic valve replacement with 120-degree rotation, freehand aortic valve replacement with intact noncoronary sinus, aortic root enlargement with intact noncoronary sinus, and total aortic root replacement. Valve function was assessed by echocardiography during the operation in 78 patients (66%) and after the operation in 77 patients (65%). One-hundred eighteen aortic valve replacements with cryopreserved aortic allografts were performed on 117 patients; mean age was 45.6 years (range 15 to 83 years) and mean follow-up was 4.6 years (range up to 11 years). Intraoperative echocardiography disclosed no significant aortic valve incompetence. There were four operative deaths (3%) and seven late deaths; freedom from valve-related mortality at 10 years was 9:3% +/- 4.55%. New York Heart Association functional status at latest follow-up was normal in 98 (94%) patients. On postoperative echocardiography, 90% had no or trivial aortic valve incompetence. Freedom from thromboembolism at 10 years was 100% and from endocarditis, 98% +/- 2.47%. Seven (6%) patients required valve explantation, four for structural deterioration. At 10 years, freedom from reoperation for allograft-related causes was 92% +/- 3.47%. Aortic valve replacement

  2. Modification of an endovascular stent graft for abdominal aortic aneurysm

    Science.gov (United States)

    Moloye, Olajompo Busola

    Endovascular surgery is currently used to treat abdominal aortic aneurysms (AAA). A stent graft is deployed to exclude blood flow from the aneurysm sac. It is an effective procedure used in preventing aneurysm rupture, with reduced patient morbidity and mortality compared to open surgical repair. Migration and leakage around the device ("endoleak") due to poor sealing of the stent graft to the aorta have raised concerns about the long-term durability of endovascular repair. A preliminary study of cell migration and proliferation is presented as a prelude to a more extensive in vivo testing. A method to enhance the biological seal between the stent graft and the aorta is proposed to eliminate this problem. This can be achieved by impregnating the stent graft with 50/50 poly (DL-lactide co glycolic acid) (PLGA) and growth factors such as basic fibroblast growth factor (bFGF) or connective tissue growth factor (CTGF), at the proximal and distal ends. It is hypothesized that as PLGA degrades it will release the growth factors that will promote proliferation and migration of aortic smooth muscle cells to the coated site, leading to a natural seal between the aorta and the stent graft. In addition, growth factor release should promote smooth muscle cell (SMC) contraction that will help keep the stent graft in place at the proximal and distal ends. It is shown that a statistically significant effect of increased cell proliferation and migration is observed for CTGF release. Less of an effect is noted for bFGF or just the PLGA. The effect is estimated to be large enough to be clinically significant in a future animal study. The long term goal of this study is to reduce migration encounter after graft deployment and to reduce secondary interventions of EVAR especially for older patients who are unfit for open surgical treatment.

  3. Aortic valve replacement for aortic stenosis with a small aortic annulus in a patient having Werner's syndrome and liver cirrhosis.

    Science.gov (United States)

    Sogawa, M; Kasuya, S; Yamamoto, K; Koshika, M; Oguma, F; Hayashi, J

    2001-12-01

    Werner's syndrome is a rare genetic disease characterized by premature aging and scleroderma-like involvement of the skin. We report a case of aortic valve replacement for severely calcified aortic valve stenosis with a small annulus in a patient suffering from Werner's syndrome and liver cirrhosis

  4. Biomechanics of sclera crosslinked using genipin in rabbit

    Directory of Open Access Journals (Sweden)

    Tai-Xiang Liu

    2017-03-01

    Full Text Available AIM: To strengthen the biomechanics of collagen by crosslinking rabbit scleral collagen with genipin to develop a new therapy for preventing myopic progression. METHODS: Ten New Zealand rabbits were treated with 0.5 mmol/L genipin injected into the sub-Tenon’s capsule in the right eyes. Untreated contralateral eyes served as the control. The treated area was cut into scleral strips measuring 4.0 mm×10.0 mm for stress-strain measurements (n=5. The remaining five treated eyes were prepared for histological examination. RESULTS: Compared to the untreated scleral strips, the genipin-crosslinked scleral strips showed that the ultimate stress and Young’s modulus at 10% strain were increased by the amplitude of 130% and 303% respectively, ultimate strain was decreased by 24%. There had no (-smooth muscle actin ((-SMA positive cells in control and treated sclera. Histologically, there was no sign of apoptosis in the sclera, choroid, and retina; and no side effects were found in the peripheral cornea and optic nerve adjacent to the treatment area. CONCLUSION: Genipin induced crosslinking of collagen can increase its biomechanical behavior by direct strengthening of the extracellular matrix in rabbit sclera, with no (-SMA expression seen in the myofibroblasts. As there is no evidence of cytotoxicity in the scleral, choroidal, and retinal cells, genipin is likely a promising agent to strengthen the weakened sclera to prevent myopic progression.

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

    Science.gov (United States)

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

    2016-06-01

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

  6. Aortic annuloplasty with aortic root reconstruction to prevent patient-prosthesis mismatch.

    Science.gov (United States)

    Hopkins, Richard A

    2006-07-01

    Part of the ongoing argument concerning patient-prosthesis mismatch (PPM) following aortic valve replacement (AVR) is due to the perception that aortic annulus enlargement procedures increase the risk and technical difficulty of aortic valve surgery. Here, an aortic root reconstruction that involves enlargement of the annulus and tailoring of the aortic root to accommodate larger stented prostheses is presented that has been personally performed in 196 patients with no technique-related surgical deaths or complications, and thus can be carried out without additional risk. This aortic root enlargement aortoplasty and annuloplasty method can be calibrated to all AVRs involving stented manufactured prostheses when these are deemed the prosthesis of choice for the patient with a relatively small annulus and/or aortic root, severe left ventricular hypertrophy, compromised LV function or a very active lifestyle, to achieve predicted EOA values > or = 1.00 cm2/m2.

  7. Sutureless Medtronic 3f Enable aortic valve replacement in a heavily calcified aortic root.

    Science.gov (United States)

    Vola, Marco; Fuzellier, Jean-Francois; Kasra, Azarnoush; Morel, Jérôme; Campisi, Salvatore; Ruggeri, Gianvito; Favre, Jean Pierre

    2013-05-01

    The case is reported of a surgical aortic valvular stenosis with a severely calcified ascending aortic root in a 76-year-old woman. The morphology and size of the aortic annulus were unsuitable for transcatheter aortic valve implantation (TAVI); thus, surgery was scheduled. Aortic calcifications allowed a transverse aortotomy 4 cm superior to the sinotubular junction, with a remote endoaortic view of the valve. A Medtronic 3f Enable sutureless bioprosthesis was then implanted after aortic annular decalcification. Sutureless bioprostheses are new tools that promise to reduce technical difficulties and cross-clamp times in minimally invasive aortic valve replacement surgery. In addition, sutureless techniques may have other possible advantages in special circumstances requiring full sternotomy access, such as in the present case.

  8. Evaluation of Biaxial Mechanical Properties of Aortic Media Based on the Lamellar Microstructure

    Directory of Open Access Journals (Sweden)

    Hadi Taghizadeh

    2015-01-01

    Full Text Available Evaluation of the mechanical properties of arterial wall components is necessary for establishing a precise mechanical model applicable in various physiological and pathological conditions, such as remodeling. In this contribution, a new approach for the evaluation of the mechanical properties of aortic media accounting for the lamellar structure is proposed. We assumed aortic media to be composed of two sets of concentric layers, namely sheets of elastin (Layer I and interstitial layers composed of mostly collagen bundles, fine elastic fibers and smooth muscle cells (Layer II. Biaxial mechanical tests were carried out on human thoracic aortic samples, and histological staining was performed to distinguish wall lamellae for determining the dimensions of the layers. A neo-Hookean strain energy function (SEF for Layer I and a four-parameter exponential SEF for Layer II were allocated. Nonlinear regression was used to find the material parameters of the proposed microstructural model based on experimental data. The non-linear behavior of media layers confirmed the higher contribution of elastic tissue in lower strains and the gradual engagement of collagen fibers. The resulting model determines the nonlinear anisotropic behavior of aortic media through the lamellar microstructure and can be assistive in the study of wall remodeling due to alterations in lamellar structure during pathological conditions and aging.

  9. Predictors of mortality after aortic valve replacement

    NARCIS (Netherlands)

    Tjang, Yanto Sandy; van Hees, Yvonne; Koerfer, Reiner; Grobbee, Diederick E.; van der Heijden, Geert J. M. G.

    Aortic valve replacement (AVR) is recommended as a standard surgical procedure for aortic valve disease. Still the evidence for commonly claimed predictors of post-AVR prognosis, in particular mortality, appears scant. This systematic review reports on the evidence for predictors of post-AVR

  10. Thoraco-abdominal aortic aneurysm branched repair

    NARCIS (Netherlands)

    Verhoeven, E. L. G.; Tielliu, I. F. J.; Ferreira, M.; Zipfel, B.; Adam, D. J.

    2010-01-01

    Open thoraco-abdominal aortic aneurysm repair is a demanding procedure with high impact on the patient and the operating team. Results from expert centres show mortality rates between 3-21%, with extensive morbidity including renal failure and paraplegia. Endovascular repair of abdominal aortic aneu

  11. Severe aortic stenosis: diagnosis, treatment and prognosis

    NARCIS (Netherlands)

    M.W.A. van Geldorp (Martijn)

    2013-01-01

    textabstractDegenerative aortic stenosis is the most common valvular heart disease in developed countries. The prevalence of severe aortic stenosis increases with age from 1% in people below 65 years of age to nearly 6% in people over the age of 85. Since the population life expectancy continues to

  12. Thoracic aortic catastrophes : towards the endovascular solution

    NARCIS (Netherlands)

    Jonker, F.H.W.

    2010-01-01

    Descending thoracic aortic catastrophes include a variety of acute pathologies of the descending thoracic aorta, which are all associated with high morbidity and mortality rates, requiring immediate intervention. For this thesis, we explored the management and outcomes of several thoracic aortic cat

  13. Transcatheter Aortic Valve Replacement in Europe

    DEFF Research Database (Denmark)

    Mylotte, Darren; Osnabrugge, Ruben L J; Windecker, Stephan;

    2013-01-01

    The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy.......The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy....

  14. Spontaneous resolution late after aortic dissection

    NARCIS (Netherlands)

    Zeebregts, CJAM; Schepens, MAAM; Vermeulen, FEE

    A 50-year-old man was operated on for acute type I (DeBakey classification) aortic dissection. The supracoronary ascending aorta was replaced with an interposition graft. Postoperative computed tomography and angiography clearly revealed a double-barrelled aortic arch, left common carotid artery and

  15. Different mechanisms of actions of genistein and quercetin on spontaneous contractions of rabbit duodenum

    Directory of Open Access Journals (Sweden)

    Diego Santos-Fagundes

    2015-07-01

    Full Text Available Flavonoids are known to relax precontracted intestinal smooth muscle and delay intestinal transit or intestinal peristalsis. The aim of this study was to determine the effects of genistein and quercetin on spontaneous contractions of rabbit duodenum in vitro in an organ bath. Genistein and quercetin (0.1-10 µM reduced the amplitude of spontaneous contractions in the longitudinal and circular smooth muscle of rabbit duodenum, but they did not modify the frequency. Bay K8644 (L-type Ca2+ channel activator, apamin, charybdotoxin, and tetraetylammonium (K+ channel blockers reverted the inhibition of amplitude of spontaneous contractions induced by genistein in longitudinal and circular smooth muscle. H-89 (protein kinase A inhibitor antagonized the reduction of the amplitude of spontaneous contractions induced by quercetin in longitudinal and circular smooth muscle of duodenum, while 2,5-dideoxiadenosine (adenylyl cyclase inhibitor reverted only the reduction of the amplitude in circular smooth muscle. In conclusion, genistein and quercetin reduce the spontaneous contractions in the duodenum by different mechanisms of actions. The effect of genistein would be mediated by Ca2+ and K+ channels, while the effect of quercetin would be mediated by cAMP and protein kinase A.

  16. The White Rabbit Project

    CERN Document Server

    Serrano, J; Cattin, M; Garcia Cota, E; Lewis, J; Moreira, P; Wlostowski, T; Gaderer, G; Loschmidt, P; Dedic, J; Bär, R; Fleck, T; Kreider, M; Prados, C; Rauch, S

    2009-01-01

    Reliable, fast and deterministic transmission of control information in a network is a need formany distributed systems. One example is timing systems, where a reference frequency is used to accurately schedule time-critical messages. TheWhite Rabbit (WR) project is a multi-laboratory and multi-company effort to bring together the best of the data transfer and timing worlds in a completely open design. It takes advantage of the latest developments for improving timing over Ethernet, such as IEEE 1588 (Precision Time Protocol) and Synchronous Ethernet. The presented approach aims for a general purpose, fieldbus-like transmission system, which provides deterministic data and timing (sub-ns accuracy and ps jitter) to around 1000 stations. It automatically compensates for fiber lengths in the order of 10 km. This paper describes the WR design goals and the specification used for the project. It goes on to describe the central component of the WR system structure - the WR switch - with theoretical considerations a...

  17. Effects of NCX 4050, a new NO donor, in rabbit and human corpus cavernosum.

    Science.gov (United States)

    Filippi, S; Crescioli, C; Vannelli, G B; Fazzini, A; Natali, A; Riffaud, J P; Maggi, M; Ledda, F

    2003-04-01

    The effects of NCX 4050, a drug belonging to a new class of NO donors, was investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and in human foetal corpora cavernosa (hfCC) smooth muscle cells. In strips of rabbit CC, NCX 4050 (0.001-100 microM) induced a concentration-dependent relaxation which was influenced neither by Nw-nitro-l-arginine-methyl-ester (l-NAME; 100 microm) nor by endothelium deprivation. The NCX 4050-induced relaxation was significantly reduced by the guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microm) and enhanced by a specific phosphodiesterase 5 inhibitor, sildenafil (300 nm). Moreover, NCX 4050 (0.01-1 microm), induced a concentration-dependent potentiation of the relaxant response induced by electrical field stimulation (EFS) in rabbit preparations pre-treated with guanethidine and indomethacin. The relaxant effect of NCX 4050 was similar to that obtained by increasing concentrations (0.001-100 microm) of sodium nitroprusside (SNP) in either rabbit or human preparations. To further investigate the activity of NCX 4050 on human corpora cavernosa, we exposed cultured hfCC smooth muscle cells to increasing concentrations of NCX 4050 and SNP. We found that both compounds dose-dependently reduced cell proliferation. The antiproliferative effect of all the concentration tested of NCX 4050 was completely blocked by ODQ (1 microm). These results suggest that in rabbit and human corpora cavernosa NCX 4050 acts by activating guanylate cyclase activity, induces smooth muscle relaxation and quiescence. Our results provide a rationale for a possible future use of NCX 4050 in the pharmacotherapy of erectile dysfunction linked to an impaired release of NO from the endothelium.

  18. Transcatheter aortic valve replacement in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Dimytri Siqueira; Alexandre Abizaid; Magaly Arrais J.; Eduardo Sousa

    2012-01-01

    Aortic stenosis is the most common native valve disease, affecting up to 5% of the elderly population. Surgical aortic valve replacement reduces symptoms and improves survival, and is the definitive therapy in patients with symptomatic severe aortic stenosis. However, despite the good results of classic surgery, risk is markedly increased in elderly patients with co-morbidities. Transcatheter aortic valve replacement (TAVR) allows implantation of a prosthetic heart valve within the diseased native aortic valve without the need for open heart surgery and cardiopulmonary bypass, offering a new therapeutic option to elderly patients considered at high surgical risk or with contraindications to surgery. To date, several multicenter registries and a randomized trial have confirmed the safety and efficacy of TAVR in those patients. In this chapter, we review the background and clinical applications of TAVR in elderly patients.

  19. Valvular and aortic diseases in osteogenesis imperfecta.

    Science.gov (United States)

    Lamanna, Arvin; Fayers, Trevor; Clarke, Sophie; Parsonage, William

    2013-10-01

    Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder caused by defective collagen synthesis with the principal manifestations of bone fragility. OI has been associated with left sided valvular regurgitation and aortic dilation. Valve and aortic surgery are technically feasible in patients with OI but are inherently high risk due to the underlying connective tissue defect. This report reviews the valvular and aortic pathology associated with OI and their management. We describe two cases of patients with OI who have significant aortic and mitral valve regurgitation, one of whom has been managed conservatively and the other who has undergone successful mitral valve repair and aortic valve replacement. The latter case represents the fifth case of mitral valve repair in a patient with OI reported in the medical literature.

  20. Selective Smoothed Finite Element Method

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The paper examines three selective schemes for the smoothed finite element method (SFEM) which was formulated by incorporating a cell-wise strain smoothing operation into the standard compatible finite element method (FEM). These selective SFEM schemes were formulated based on three selective integration FEM schemes with similar properties found between the number of smoothing cells in the SFEM and the number of Gaussian integration points in the FEM. Both scheme 1 and scheme 2 are free of nearly incompressible locking, but scheme 2 is more general and gives better results than scheme 1. In addition, scheme 2 can be applied to anisotropic and nonlinear situations, while scheme 1 can only be applied to isotropic and linear situations. Scheme 3 is free of shear locking. This scheme can be applied to plate and shell problems. Results of the numerical study show that the selective SFEM schemes give more accurate results than the FEM schemes.

  1. α-compactness in smooth topological spaces

    Directory of Open Access Journals (Sweden)

    Chun-Kee Park

    2003-01-01

    Full Text Available We introduce the concepts of smooth α-closure and smooth α-interior of a fuzzy set which are generalizations of smooth closure and smooth interior of a fuzzy set defined by Demirci (1997 and obtain some of their structural properties.

  2. Inhibition of rac1 reduces PDGF-induced reactive oxygen species and proliferation in vascular smooth muscle cells.

    OpenAIRE

    2001-01-01

    In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC)...

  3. Ouabain sensitive Na+/K+-pump regulates other membrane transporters in the microdomain of smooth muscle cells

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Nilsson, Holger; Aalkjær, Christian

    Ouabain, a specific inhibitor of the Na+/K+-pump, has previously been shown to interfere with intercellular communication. We have demonstrated a mechanism of this action of ouabain (1). We have showed that gap junctions between vascular smooth muscle cells (SMCs) are regulated through......+/K+-pump-containing microdomain is functionally linked to KATP channels via the local ion homeostasis and that this interaction can be bidirectional (1;2). [Ca2+]i in individual SMCs was imaged simultaneously with isometric force in rat mesenteric small arteries. Paired cultured rat aortic smooth muscle cells (A7r5) were used...

  4. [Modern aortic surgery in Marfan syndrome--2011].

    Science.gov (United States)

    Kallenbach, K; Schwill, S; Karck, M

    2011-09-01

    Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000 births, leading to a fibrillin connective tissue disorder with manifestations in the skeleton, eye, skin, dura mater and in particular the cardiovascular system. Since other syndromes demonstrate similar vascular manifestations, but therapy may differ significantly, diagnosis should be established using the revised Ghent nosology in combination with genotypic analysis in specialized Marfan centres. The formation of aortic root aneurysms with the subsequent risk of acute aortic dissection type A (AADA) or aortic rupture limits life expectancy in patients with Marfan syndrome. Therefore, prophylactic replacement of the aortic root needs to be performed before the catastrophic event of AADA can occur. The goal of surgery is the complete resection of pathological aortic tissue. This can be achieved with excellent results by using a (mechanically) valved conduit that replaces both the aortic valve and the aortic root (Bentall operation). However, the need for lifelong anticoagulation with Coumadin can be avoided using the aortic valve sparing reimplantation technique according to David. The long-term durability of the reconstructed valve is favourable, and further technical improvements may improve longevity. Although results of prospective randomised long-term studies comparing surgical techniques are lacking, the David operation has become the surgical method of choice for aortic root aneurysms, not only at the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch is performed under moderate hypothermic circulatory arrest combined with antegrade cerebral perfusion using a heart-lung machine, which we also use in thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a Marfan centre is pivotal for the early detection of pathological changes on the diseased aorta.

  5. Inhibition of EP4 signaling attenuates aortic aneurysm formation.

    Directory of Open Access Journals (Sweden)

    Utako Yokoyama

    Full Text Available BACKGROUND: Aortic aneurysm is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Activation of prostaglandin E(2 (PGE(2 is known to increase the expression of matrix metalloproteinase (MMP and the release of inflammatory cytokines, and may thus exacerbate abdominal aortic aneurysm (AAA formation. We hypothesized that selective blocking of PGE(2, in particular, EP4 prostanoid receptor signaling, would attenuate the development of AAA. METHODS AND FINDINGS: Immunohistochemical analysis of human AAA tissues demonstrated that EP4 expression was greater in AAA areas than that in non-diseased areas. Interestingly, EP4 expression was proportional to the degree of elastic fiber degradation. In cultured human aortic smooth muscle cells (ASMCs, PGE(2 stimulation increased EP4 protein expression (1.4 ± 0.08-fold, and EP4 stimulation with ONO-AE1-329 increased MMP-2 activity and interleukin-6 (IL-6 production (1.4 ± 0.03- and 1.7 ± 0.14-fold, respectively, P<0.05. Accordingly, we examined the effect of EP4 inhibition in an ApoE(-/- mouse model of AAA infused with angiotensin II. Oral administration of ONO-AE3-208 (0.01-0.5 mg/kg/day, an EP4 antagonist, for 4 weeks significantly decreased the formation of AAA (45-87% reduction, P<0.05. Similarly, EP4(+/-/ApoE(-/- mice exhibited significantly less AAA formation than EP4(+/+/ApoE(-/- mice (76% reduction, P<0.01. AAA formation induced by periaortic CaCl(2 application was also reduced in EP4(+/- mice compared with wild-type mice (73% reduction, P<0.001. Furthermore, in human AAA tissue organ cultures containing SMCs and macrophages, doses of the EP4 antagonist at 10-100 nM decreased MMP-2 activation and IL-6 production (0.6 ± 0.06- and 0.7 ± 0.06-fold, respectively, P<0.05 without increasing MMP-9 activity or MCP-1 secretion. Thus, either pharmacological or genetic EP4 inhibition attenuated AAA formation in multiple mouse and human models

  6. Wetting on smooth micropatterned defects

    CERN Document Server

    Debuisson, Damien; Senez, Vincent; Arscott, Steve

    2011-01-01

    We develop a model which predicts the contact angle hysteresis introduced by smooth micropatterned defects. The defects are modeled by a smooth function and the contact angle hysteresis is explained using a tangent line solution. When the liquid micro-meniscus touches both sides of the defect simultaneously, depinning of the contact line occurs. The defects are fabricated using a photoresist and experimental results confirm the model. An important point is that the model is scale-independent, i.e. the contact angle hysteresis is dependent on the aspect ratio of the function, not on its absolute size; this could have implications for natural surface defects.

  7. A new method to identify dynamic transduction properties of aortic baroreceptors.

    Science.gov (United States)

    Sugimachi, M; Imaizumi, T; Sunagawa, K; Hirooka, Y; Todaka, K; Takeshita, A; Nakamura, M

    1990-03-01

    We identified, in 17 alpha-chloralose-anesthetized rabbits, the dynamic transduction characteristics of the aortic arch baroreceptors using a "white-noise technique." We recorded aortic pressure and aortic depressor nerve activity while perturbing pressure by rapid, intermittent ventricular pacing (400 beats/min). Dividing the cross-power spectrum between nerve activity and pressure by the power spectrum of pressure yielded the transfer function. The gain of the transfer function increased threefold as the frequency increased from 0.005 to 5 Hz, suggesting that the baroreceptors responded primarily to dynamic rather than to static changes in pressure. To quantify the nonlinear properties of baroreceptor transduction, we compared measured instantaneous nerve activity with that linearly predicted. We demonstrated that the major nonlinearity was attributable to "threshold". The overall baroreceptor transduction properties could be represented by a cascade connection of a linear subsystem followed by a nonlinear subsystem with threshold. The white-noise technique made it possible to identify the unbiased linear properties in a nonlinear system, and thus was very useful in identifying complex biological systems.

  8. Reoperation on aortic disease in patients with previous aortic valve surgery

    Institute of Scientific and Technical Information of China (English)

    SUN Xiao-gang; ZHANG Liang; YU Cun-tao; QIAN Xiang-yang; CHANG Qian

    2013-01-01

    Background Aortic valve replacement (AVR) is a safe and effective method in the treatment of aortic valve diseases.This study aimed to increase the understanding on re-treatment of aortic diseases after aortic valve surgery through a retrospective analysis of 47 related cases.Methods Forty-seven patients (38 males and 9 females) with previous aortic valve surgery have received reoperation on aorta from January 2003 to June 2012,and the mean interval time of re-intervention to aortic disease was 6 years ((6.0± 3.8) years).The secondary aortic surgery included aortic root replacement (14 cases),ascending aorta replacement (10 cases),aortic root/ascending aorta plus total arch replacement with stented elephant trunk implantation (21 cases),and total thoracoabdominal aorta replacement (2 cases).All these patients have received outpatient re-exams or follow-up by phone calls.Results After the initial aortic valve replacement,patients suffered from aortic dissection (25 cases,53%),ascending aortic aneurysm (12 cases,26%) or aortic root aneurysm (10 cases,21%).Diameter in ascending aorta increased (5.2±7.1) mm per year and aortic sinus (3.3±3.1) mm per year.The annual growth value of diameter in ascending aorta was higher in patients with rheumatic heart disease than that in Marfan syndrome (P<0.05).All 47 patients have received reoperation on aorta.One patient died in operating room because aortic dissection seriously involved right coronary artery.Seven patients had renal insufficiency after operation; neurological complications occurred in 14 patients including 7 patients with stroke and the others with transient brain dysfunction.All patients were followed up,the mean survival time was (97.25±17.63) months,95% confidence interval was 55.24-73.33 months.Eight cases were died during follow-up and five-year survival rate was 83%.Conclusion To reduce the aortic adverse events after first aortic valve surgery,it is necessary to actively treat and strictly

  9. Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat.

    Science.gov (United States)

    Bunker, Aaron K; Arce-Esquivel, Arturo A; Rector, R Scott; Booth, Frank W; Ibdah, Jamal A; Laughlin, M Harold

    2010-06-01

    We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium-dependent relaxation from 13 to 20 wk of age (20-35%) and from 13 to 40 wk of age (35-50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with N(G)-nitro-l-arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium-dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS.

  10. Quantitative image analysis for planning of aortic valve replacement

    NARCIS (Netherlands)

    Elattar, M.A.I.M.

    2016-01-01

    Aortic stenosis is the most common and frequent cause of sudden death among all valvular heart diseases. Symptomatic aortic stenosis is considered to be a fatal disease if left untreated. Aortic valve replacement is the mainstay of treatment of symptomatic aortic stenosis. Traditional treatment of s

  11. Quantitative image analysis for planning of aortic valve replacement

    NARCIS (Netherlands)

    Elattar, M.A.I.M.

    2016-01-01

    Aortic stenosis is the most common and frequent cause of sudden death among all valvular heart diseases. Symptomatic aortic stenosis is considered to be a fatal disease if left untreated. Aortic valve replacement is the mainstay of treatment of symptomatic aortic stenosis. Traditional treatment of

  12. Rare, Non-Synonymous Variant in the Smooth Muscle-Specific Isoform of Myosin Heavy Chain, MYH11, R247C, Alters Force Generation in the Aorta and Phenotype of Smooth Muscle Cells

    Science.gov (United States)

    Kuang, Shao-Qing; Kwartler, Callie S.; Byanova, Katerina L.; Pham, John; Gong, Limin; Prakash, Siddharth K.; Huang, Jian; Kamm, Kristine E.; Stull, James T.; Sweeney, H. Lee; Milewicz, Dianna M.

    2013-01-01

    Rationale Mutations in MYH11 cause autosomal dominant inheritance of thoracic aortic aneurysms and dissections. At the same time, rare, non-synonymous variants in MYH11 that are predicted to disrupt protein function but do not cause inherited aortic disease are common in the general population and the vascular disease risk associated with these variants is unknown. Objective To determine the consequences of the recurrent MYH11 rare variant, R247C, through functional studies in vitro and analysis of a knock-in mouse model with this specific variant, including assessment of aortic contraction, response to vascular injury, and phenotype of primary aortic smooth muscle cells (SMCs). Methods and Results The steady state ATPase activity (actin-activated) and the rates of phosphate and ADP release were lower for the R247C mutant myosin than for the wild-type, as was the rate of actin filament sliding in an in vitro motility assay. Myh11R247C/R247C mice exhibited normal growth, reproduction, and aortic histology but decreased aortic contraction. In response to vascular injury, Myh11R247C/R247C mice showed significantly increased neointimal formation due to increased SMC proliferation when compared with the wild-type mice. Primary aortic SMCs explanted from the Myh11R247C/R247C mice were de-differentiated compared with wild-type SMCs based on increased proliferation and reduced expression of SMC contractile proteins. The mutant SMCs also displayed altered focal adhesions and decreased Rho activation, associated with decreased nuclear localization of myocardin-related transcription factor-A. Exposure of the Myh11R247C/R247C SMCs to a Rho activator rescued the de-differentiated phenotype of the SMCs. Conclusions These results indicate that a rare variant in MYH11, R247C, alters myosin contractile function and SMC phenotype, leading to increased proliferation in vitro and in response to vascular injury. PMID:22511748

  13. Bicuspid Aortic Valve Disease and Ascending Aortic Aneurysms: Gaps in Knowledge

    Directory of Open Access Journals (Sweden)

    Katie L. Losenno

    2012-01-01

    Full Text Available The bicuspid aortic valve is the most common congenital cardiac anomaly in developed nations. The abnormal bicuspid morphology of the aortic valve results in valvular dysfunction and subsequent hemodynamic derangements. However, the clinical presentation of bicuspid aortic valve disease remains quite heterogeneous with patients presenting from infancy to late adulthood with variable degrees of valvular stenosis and insufficiency and associated abnormalities including aortic coarctation, hypoplastic left heart structures, and ascending aortic dilatation. Emerging evidence suggests that the heterogeneous presentation of bicuspid aortic valve phenotypes may be a more complex matter related to congenital, genetic, and/or connective tissue abnormalities. Optimal management of patients with BAV disease and associated ascending aortic aneurysms often requires a thoughtful approach, carefully assessing various risk factors of the aortic valve and the aorta and discerning individual indications for ongoing surveillance, medical management, and operative intervention. We review current concepts of anatomic classification, pathophysiology, natural history, and clinical management of bicuspid aortic valve disease with associated ascending aortic aneurysms.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 18 and 36 and 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.

  16. [Aortic valve replacement as an independent predictive factor for later development of aortic dissection].

    Science.gov (United States)

    von Kodolitsch, Y; Simic, O; Bregenzer, T; Dresler, C; Haverich, A; Nienaber, C A

    1998-08-01

    Dissection of the ascending aorta (type A) following later after aortic valve replacement has been described with increasing frequency. This study analyzes the role of aortic valve replacement for the evolution of late dissection. In a series of 80 consecutive patients with type A dissection, a previous aortic valve replacement had been performed in 12 cases (15%). In addition to arterial hypertension (p syndrome (p factor for type A dissection. Dissection occurred 3 +/- 4 years after aortic valve replacement with a clinical and anatomical profile similar to classic dissection as proven by comparison to a group of 62 patients with classic dissection associated with arterial hypertension or Marfan syndrome. With 75% and 66%, respectively, 30 day and 1 year survival of patients with dissection following later after aortic valve replacement was similar to patients with classic type A dissection. Extensive thinning and/or fragility (p associated with a high risk for late dissection; this finding was substantiated by comparison to a control group of 10 consecutive patients with a similarly dilated aortic root but no dissection. Type and diameter of valve prostheses, cross-clamp time, NYHA functional class, and left ventricular ejection fraction were unrelated to late dissection. Previous aortic valve replacement is an independent predisposing factor for a dissection of the ascending aorta later. At the time of aortic valve replacement, prophylactic replacement or wrapping of the ascending aorta should be considered in patients with a thinned/fragile aortic wall even without a markedly dilated aortic root.

  17. Mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy.

    Science.gov (United States)

    Ayme-Dietrich, Estelle; Lawson, Roland; Gasser, Bernard; Dallemand, Robert; Bischoff, Nicolas; Monassier, Laurent

    2012-04-01

    The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year-old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  18. Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm

    DEFF Research Database (Denmark)

    Waeckel, L.; Badier-Commander, C.; Damery, T.

    2015-01-01

    Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose of this work was to study the endothelial function in wild-type C57BL/6 (BL) and transgenic mice expressing...... not affected in BLSL and AR. However, in ARSL, endothelium-dependent relaxations (acetylcholine, UK-14304) were significantly reduced, and this dysfunction was similar in aortae without or with aneurysms. The endothelial impairment was unaffected by catalase, superoxide-dismutase mimetic, radical scavengers......, cyclooxygenase inhibition, or TP-receptor blockade and could not be attributed to sGC oxidation. Thus, ARSL is a severe hypertension model developing aortic aneurysm. A vascular dysfunction, involving both endothelial (reduced role of NO) and smooth muscle cells, precedes aneurysms formation and, paradoxically...

  19. Biophysical induction of vascular smooth muscle cell podosomes.

    Directory of Open Access Journals (Sweden)

    Na Young Kim

    Full Text Available Vascular smooth muscle cell (VSMC migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu, however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs.

  20. Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation.

    Science.gov (United States)

    Eliason, Jonathan L; Hannawa, Kevin K; Ailawadi, Gorav; Sinha, Indranil; Ford, John W; Deogracias, Michael P; Roelofs, Karen J; Woodrum, Derek T; Ennis, Terri L; Henke, Peter K; Stanley, James C; Thompson, Robert W; Upchurch, Gilbert R

    2005-07-12

    Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. Control, rabbit serum-treated (RS; n=27) or anti-neutrophil-antibody-treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN-treated mice became neutropenic (mean, 349 cells/microL), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104+/-14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN-treated mice exhibited a mean AD increase of 42+/-33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN-treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1alpha chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8-positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8-deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134+/-7.9% versus 154+/-9.9%; P=0.603), which suggests that MMP-8

  1. Detection of histidine decarboxylase mRNA in human vascular smooth muscle and endothelial cells.

    Science.gov (United States)

    Tippens, A S; Gruetter, C A

    2004-06-01

    The objective of this study was to investigate histamine synthesis capability of human vascular smooth muscle and endothelial cells by detecting histidine decarboxylase (HDC) mRNA. HDC catalyzes exclusively the formation of histamine in mammalian cells. Experiments utilizing nested reverse transcription-polymerase chain reaction (nRT-PCR) were conducted to detect the presence of HDC mRNA. Human aortic smooth muscle cells (HAoSMC) and human aortic endothelial cells (HAEC) were cultured and RNA was extracted and amplified using two sets of HDC-specific primers. Rat liver and kidney RNA were isolated and amplified to serve as positive and negative controls, respectively. Gel electrophoresis of HAoSMC, HAEC and liver mRNA revealed bands coinciding with an expected product size of 440 base pairs. Sequence analysis revealed that the observed bands were the appropriate HDC amplicons. These findings are the first to indicate the presence of HDC mRNA in vascular smooth muscle cells and confirm the presence of HDC mRNA in endothelial cells which is consistent with an ability of these cell types to synthesize histamine in the vascular wall.

  2. Voltage-dependent effects of barnidipine in rat vascular smooth muscle.

    Science.gov (United States)

    Wegener, J W; Korstanje, C; Nawrath, H

    2003-08-01

    The effects of the dihydropyridine nifedipine and its more lipophilic congener, barnidipine, were investigated in smooth muscle preparations from the rat in resting and depolarizing conditions. Both drugs relaxed precontracted aortic rings more potently in depolarizing conditions, barnidipine being more potent than nifedipine. Currents through Ca2+ channels in rat vascular smooth muscle cells (A7r5) and in isolated rat cardiomyocytes were reduced more potently by both drugs at a holding potential of -40 mV than at -80 mV. However, barnidipine and nifedipine were more effective in reducing the current in A7r5 cells than in cardiomyocytes. The IC(50) obtained in aortic rings and in A7r5 cells were similar for barnidipine but an order of magnitude different for nifedipine. The results show that, in depolarizing conditions, barnidipine was more effective than nifedipine. It is suggested that the higher potency of barnidipine acting in vascular smooth muscle is related to both a higher affinity to the inactivated state of vascular Ca2+ channels and to a more lipophilic property as compared with nifedipine.

  3. Teratology studies in the rabbit.

    Science.gov (United States)

    Allais, Linda; Reynaud, Lucie

    2013-01-01

    The rabbit is generally the non-rodent species or second species after the rat recommended by the regulatory authorities and is part of the package of regulatory reproductive studies for the detection of potential embryotoxic and/or teratogenic effects of pharmaceuticals, chemicals, food additives, and other compounds, including vaccines (see Chapters 1-7).Its availability, practicality in housing and in mating as well as its large size makes the rabbit the preferred choice as a non-rodent species. The study protocols are essentially similar to those established for the rat (Chapter 9), with some particularities. The study designs are well defined in guidelines and are relatively standardized between testing laboratories across the world.As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations.

  4. High pacing rates for management of aortic insufficiency after balloon aortic valvuloplasty or transcatheter aortic valve replacement.

    Science.gov (United States)

    Ali, Omar; Salinger, Michael H; Levisay, Justin P; Feldman, Ted

    2014-01-01

    Aortic insufficiency (AI) after transcatheter aortic valve replacement (TAVR) is difficult to manage when associated with congestive heart failure. AI after balloon aortic valvuloplasty (BAV) may be catastrophic, especially in patients who are not candidates for TAVR. We describe the use of urgent temporary pacing, followed by permanent pacing, to increase the heart rate to diminish diastolic filling time for the short term management of AI after BAV or TAVR. The strategy is particularly useful in patients who already have permanent pacemakers, which are common in this population.

  5. Dynamic smoothing of nanocomposite films

    NARCIS (Netherlands)

    Pei, Y.T.; Turkin, A; Chen, C.Q.; Shaha, K.P.; Vainshtein, D.; Hosson, J.Th.M. De

    2010-01-01

    In contrast to the commonly observed dynamic roughening in film growth we have observed dynamic smoothing in the growth of diamondlike-carbon nanocomposite (TiC/a-C) films up to 1.5 mu m thickness. Analytical and numerical simulations, based on the Edwards-Wilkinson model and the Mullins model, visu

  6. Nonlinear smoothing for random fields

    NARCIS (Netherlands)

    Aihara, Shin Ichi; Bagchi, Arunabha

    1995-01-01

    Stochastic nonlinear elliptic partial differential equations with white noise disturbances are studied in the countably additive measure set up. Introducing the Onsager-Machlup function to the system model, the smoothing problem for maximizing the modified likelihood functional is solved and the exp

  7. Two-Year Outcomes in Patients With Severe Aortic Valve Stenosis Randomized to Transcatheter Versus Surgical Aortic Valve Replacement

    DEFF Research Database (Denmark)

    Søndergaard, Lars; Steinbrüchel, Daniel Andreas; Ihlemann, Nikolaj

    2016-01-01

    BACKGROUND: The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize all-comers with severe native aortic valve stenosis to either transcatheter aortic valve replacement (TAVR) with the CoreValve self-expanding bioprosthesis or surgical aortic valve replacement (SAVR), inclu...... population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01057173....

  8. [Review] Mary Toft's Rabbit Tale

    OpenAIRE

    Jones, Emrys

    2013-01-01

    Originally broadcast in April 2011 and aired again by BBC Radio 4 this November, Mary Toft’s Rabbit Tale is a radio drama retelling the story of its titular fraudster’s brief notoriety. With a high-profile cast – including singer Will Young as Toft’s husband and Rupert Graves as man-midwife, John Howard – the play explores a number of issues related to the alleged rabbit births of 1726 and their impact on public discourse of the time.

  9. Aortic reconstruction with bovine pericardial grafts

    Directory of Open Access Journals (Sweden)

    Silveira Lindemberg Mota

    2003-01-01

    Full Text Available INTRODUCTION: Glutaraldehyde-treated crimped bovine pericardial grafts are currently used in aortic graft surgery. These conduits have become good options for these operations, available in different sizes and shapes and at a low cost. OBJECTIVE:To evaluate the results obtained with bovine pericardial grafts for aortic reconstruction, specially concerning late complications. METHOD: Between January 1995 and January 2002, 57 patients underwent different types of aortic reconstruction operations using bovine pericardial grafts. A total of 29 (50.8% were operated on an urgent basis (mostly acute Stanford A dissection and 28 electively. Thoracotomy was performed in three patients for descending aortic replacement (two patients and aortoplasty with a patch in one. All remaining 54 underwent sternotomy, cardiopulmonary bypass and aortic resection. Deep hypothermia and total circulatory arrest was used in acute dissections and arch operations. RESULTS: Hospital mortality was 17.5%. Follow-up was 24.09 months (18.5 to 29.8 months confidence interval and complication-free actuarial survival curve was 92.3% (standard deviation ± 10.6. Two patients lately developed thoracoabdominal aneurysms following previous DeBakey II dissection and one died from endocarditis. One "patch" aortoplasty patient developed local descending aortic pseudoaneurysm 42 months after surgery. All other patients are asymptomatic and currently clinically evaluated with echocardiography and CT scans, showing no complications. CONCLUSION: Use of bovine pericardial grafts in aortic reconstruction surgery is adequate and safe, with few complications related to the conduits.

  10. Repair for acquired aortic valve disease.

    Science.gov (United States)

    Antunes, M J

    1996-10-01

    The favorable results of mitral valvuloplasty when compared with valve replacement have renewed the interest of many surgeons in aortic valve repair. However, these efforts have, for the most part, been unsuccessful. Also, the results of aortic valve replacement are usually better than those of mitral valve replacement. Yet, some patients appear to derive benefit from a conservative aortic valve procedure. The best examples are mild or moderate aortic valve disease associated with mitral valve or coronary artery disease, which constitute the primary indication for operation, where "prophylactic" aortic valve replacement does not appear justifiable. Other possible indications for aortic valvuloplasty includes patient's lack of compliance or contraindication to anticoagulation in young patients. Senile aortic stenosis, in very old patients with a small annulus, preserved leaflet morphology and nonsignificant commissural fusion should be considered for repair. However, since the procedure is not easily reproducible and the results not uniformly predictable, it cannot be recommended for generalized use. Nonetheless, experienced surgeons should be encouraged to continue these efforts.

  11. Hybrid treatment of recurring thoracoabdominal aortic aneurysm concomitant with retrograde type A aortic dissection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min-hong; GUO Wei; DU Xin; XIONG Jiang

    2010-01-01

    So far, standard therapy of complex thoracoabdominal aortic disease is open surgical repair requiring aortic clamping and replacement of the involved segment.Despite significant improvements, morbidity and mortality of open surgery remain high.I As a result, open surgery is often withheld owing to severe comorbidities of the patients. Endovascular technique has emerged as an alternative for treatment of these diseases in high risk patients,2 and has enlarged the options of treatment of complex aortic diseases. However, an endovascular approach alone is often deemed unsuitable for some complex aortic disorders because of the close proximity of the supraaortic or visceral branches. A hybrid open-endovascular approach has therefore been proposed as a viable alternative. We present here a unique patient with recurring thoracoabdominal aortic aneurysm (TAAA) concomitant with an aortic dissection (AD) treated by a hybrid open-endovascular approach.

  12. Aortic stenosis: From diagnosis to optimal treatment

    Directory of Open Access Journals (Sweden)

    Tavčiovski Dragan

    2008-01-01

    Full Text Available Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is the first characteristic lesion of the cusps, which is considered today as the process similar to atherosclerosis. Progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. It is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Proper physical examination remains an essential diagnostic tool in aortic stenosis. Recognition of characteristic systolic murmur draws attention and guides further diagnosis in the right direction. Doppler echocardiography is an ideal tool to confirm diagnosis. It is well known that exercise tests help in stratification risk of asymptomatic aortic stenosis. Serial measurements of brain natriuretic peptide during a follow-up period may help to identify the optimal time for surgery. Heart catheterization is mostly restricted to preoperative evaluation of coronary arteries rather than to evaluation of the valve lesion itself. Currently, there is no ideal medical treatment for slowing down the disease progression. The first results about the effect of ACE inhibitors and statins in aortic sclerosis and stenosis are encouraging, but there is still not enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are I class indication for aortic valve replacement. Aortic valve can be replaced with a biological or prosthetic valve. There is a possibility of percutaneous aortic valve implantation and transapical operation for patients that are contraindicated for standard cardiac surgery.

  13. Valvular Aortic Stenosis: A Proteomic Insight

    Directory of Open Access Journals (Sweden)

    Fernando Vivanco

    2010-02-01

    Full Text Available Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area. Summary: Until recently, aortic stenosis (AS was considered a passive process secondary to calcium deposition in the aortic valves. However, it has recently been highlighted that the risk factors associated with the development of calcified AS in the elderly are similar to those of coronary artery disease. Furthermore, degenerative AS shares histological characteristics with atherosclerotic plaques, leading to the suggestion that calcified aortic valve disease is a chronic inflammatory process similar to atherosclerosis. Nevertheless, certain data does not fit with this theory making it necessary to further study this pathology. The aim of this study is to develop an effective protein extraction protocol for aortic stenosis valves such that proteomic analyses can be performed on these structures. In the present work we have defined a rapid, reproducible and effective method to extract proteins and that is compatible with 2-DE, 2D-DIGE and MS techniques. Defining the protein profile of this tissue is an important and challenging task that will help to understand the mechanisms of physiological/pathological processes in aortic stenosis valves.

  14. Effects of rosiglitazone on contralateral iliac artery after vascular injury in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    Baroncini Liz

    2008-05-01

    Full Text Available Abstract Background The objective was to evaluate the effects of rosiglitazone on iliac arteries of hypercholesterolemic rabbits undergoing balloon catheter injury in the contralateral iliac arteries. Methods White male rabbits were fed a hypercholesterolemic diet for 6 weeks and divided into two groups as follows: rosiglitazone group, 14 rabbits treated with rosiglitazone (3 mg/Kg body weight/day during 6 weeks; and control group, 18 rabbits without rosiglitazone treatment. All animals underwent balloon catheter injury of the right iliac artery on the fourteenth day of the experiment. Results There was no significant difference in intima/media layer area ratio between the control group and the rosiglitazone group. Rosiglitazone did not reduce the probability of lesions types I, II, or III (72.73% vs. 92.31%; p = 0.30 and types IV or V (27.27% vs. 7.69%; p = 0.30. There were no differences in the extent of collagen type I and III deposition or in the percentage of animals with macrophages in the intima layer. The percentage of rabbits with smooth muscle cells in the intima layer was higher in rosiglitazone group (p = 0.011. Conclusion These findings demonstrate that rosiglitazone given for 6 weeks did not prevent atherogenesis at a vessel distant from the injury site.

  15. The future of aortic surgery in Europe

    DEFF Research Database (Denmark)

    Czerny, Martin; Bachet, Jean; Bavaria, Joseph;

    2012-01-01

    the interested reader with an overview of how aortic surgery and (perhaps more accurately) aortic medicine has evolved in Europe, and its present standing; also to provide a glimpse into the future, trying to disseminate the thoughts of a group of people actively involved in the development of aortic medicine......At least every ten years, each specialty should reflect upon its past, its present and its future, in order to be able to reconfirm the direction in which it is headed, to adopt suggestions from inside and outside and, consequently, to improve. As such, the aim of this manuscript is to provide...

  16. Bacillus cereus endocarditis in native aortic valve.

    Science.gov (United States)

    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.

  17. Mycotic Aneurysm of the Aortic Arch

    Directory of Open Access Journals (Sweden)

    Ji Hye Seo

    2014-08-01

    Full Text Available A mycotic aneurysm of the thoracic aorta is rare. We report a case of mycotic aneurysm that developed in the aortic arch. An 86-year-old man was admitted with fever and general weakness. Blood culture yielded methicillin-resistant Staphylococcus aureus. Chest X-ray showed an enlarged aortic arch, and computed tomography scan revealed an aneurysm in the aortic arch. The patient was treated only with antibiotics and not surgically. The size of the aneurysm increased rapidly, resulting in bronchial obstruction and superimposed pneumonia. The patient died of respiratory failure.

  18. Structural valve deterioration after aortic valve replacement with Medtronic freestyle stentless porcine aortic root bioprostheses.

    Science.gov (United States)

    Nishida, Hidefumi; Komiya, Tatsuhiko; Sakaguchi, Genichi; Shimamoto, Takeshi

    2014-01-01

    The Medtronic freestyle aortic root bioprosthesis (Medtronic, Inc., Minneapolis, MN, USA) is a stentless valve with an effective orifice area that is larger than that observed on other bioprostheses. However, there have been sporadic reports of structural valve deterioration (SVD), such as aortic root wall rupture, leaflet tearing, and pseudoaneurysm formation. We report five cases of SVD of freestyle aortic root bioprostheses. © 2013 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc.

  19. Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2010-01-01

    Full Text Available Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 μm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain and immunocytochemically using a DAKO LSAB+/HRP technique to identify α-smooth muscle actin (α-SMA, vimentin, myosin heavy chains (MHC, desmin, S-100 protein, CD45 and CD68 (DAKO specification. Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs are present, which express a α-SMA and vimentin (but without MHC or desmin expression, as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection. Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the

  20. Stent graft implantation in an aortic pseudoaneurysm associated with a fractured Cheatham-Platinum stent in aortic coarctation.

    Science.gov (United States)

    Kuhelj, Dimitrij; Berden, Pavel; Podnar, Tomaž

    2016-03-01

    We report a case of aortic pseudoaneurysm associated with a fractured bare Cheatham-Platinum stent following stenting for aortic coarctation. These complications were recognised 6 years after the implantation procedure and were successfully managed by percutaneous stent graft implantation. Staged approach for stent dilatation might prevent development of aortic pseudoaneurysms. In addition, careful follow-up is warranted after stenting for aortic coarctation, particularly in patients with recognised aortic wall injury.

  1. Patient-prosthesis mismatch: surgical aortic valve replacement versus transcatheter aortic valve replacement in high risk patients with aortic stenosis.

    Science.gov (United States)

    Ghanta, Ravi K; Kron, Irving L

    2016-10-01

    Patient prosthesis mismatch (PPM) can occur when a prosthetic aortic valve has an effective orifice area (EOA) less than that of a native valve. A recent study by Zorn and colleagues evaluated the incidence and significance of PPM in high risk patients with severe aortic stenosis who were randomized to transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). TAVR is associated with decreased incidence of severe PPM compared to traditional SAVR valves. Severe PPM increases risk for death at 1 year postoperatively in high risk patients. The increased incidence of PPM is largely due to differences in valve design and should encourage development of newer SAVR valves to reduce risk for PPM. In addition more vigorous approaches to root enlargement in small annulus should be performed with SAVR to prevent PPM.

  2. Isolated Diffuse Supravalvular Aortic Stenosis with Severe Aortic Narrowing in a 41-Year-Old Man.

    Science.gov (United States)

    Namana, Vinod; Siddiqui, Sabah; Balasubramanian, Ram; Shani, Jacob; Sadiq, Adnan

    2017-08-01

    Isolated supravalvular aortic stenosis in adults is a rare form of left ventricular outflow tract obstruction. We describe a case in a 41-year-old man in whom the supravalvular aorta had narrowed to approximately the size of the left anterior descending coronary artery. The patient underwent aortic surgery with replacement of the ascending aorta and repair of supravalvular aortic stenosis with a pantaloon graft. A postoperative echocardiogram showed substantial improvement: the mean gradient across the aorta had fallen from 48 to 8 mmHg. Surgery is the definitive treatment in symptomatic patients with supravalvular aortic stenosis.

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Iatrogenic hemolytic anemia and endocarditis in New Zealand white rabbits secondary to Achromobacter xylosoxidans infection.

    Science.gov (United States)

    Allison, Sarah O; Artwoh, James E; Fortman, Jeffrey D; Pogwizd, Steven; Jeanes, Jodi; Koske, Sarah; Pinkerton, Marie E; Haschek, Wanda M; Messick, Joanne

    2007-11-01

    During a 3-mo period, 9 of the 15 New Zealand White rabbits used in a heart failure study developed a hemolytic anemia. The heart failure model involved the creation of an aortic insufficiency (AI) followed 2 to 6 wk later by the creation of an aortic stenosis (AS). None of the 9 animals that developed hemolytic anemia responded to medical management, and 6 of the 9 were euthanized for humane concerns. Necropsies and blood cultures were performed on all anemic animals; 7 of these cultures yielded growth of Achromobacter xylosoxidans. In addition, cultures from the heart valves of 2 rabbits yielded growth of Achromobacter xylosoxidans. We presume that the endocarditis caused by Achromobacter xylosoxidans led to the mechanical damage of red blood cells (RBCs) and subsequent intravascular hemolysis or splenic destruction of damaged RBCs, resulting in a severe, regenerative hemolytic anemia. Achromobacter xylosoxidans is an aerobic, catalase-positive, oxidase-positive, gram-negative bacillus. This organism is an environmentally resistant and opportunistic bacterium that typically inhabits aqueous environments. Microbial samples from the investigator's laboratory and equipment were collected to identify the source of the bacteria. A pressure transducer and bag of intravenous fluid were identified as sources of contamination.

  6. Very Smooth Points of Spaces of Operators

    Indian Academy of Sciences (India)

    T S S R K Rao

    2003-02-01

    In this paper we study very smooth points of Banach spaces with special emphasis on spaces of operators. We show that when the space of compact operators is an -ideal in the space of bounded operators, a very smooth operator attains its norm at a unique vector (up to a constant multiple) and ( ) is a very smooth point of the range space. We show that if for every equivalent norm on a Banach space, the dual unit ball has a very smooth point then the space has the Radon–Nikodým property. We give an example of a smooth Banach space without any very smooth points.

  7. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...... the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation) of ERK1/2 as a functional signal molecule for endothelin receptor activity. RESULTS: Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 microM). The activation of ERK1/2...... was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2...

  8. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...

  9. De Novo ACTA2 Mutation Causes a Novel Syndrome of Multisystemic Smooth Muscle Dysfunction

    Science.gov (United States)

    Milewicz, Dianna M.; Østergaard, John R.; Ala-Kokko, Leena M.; Khan, Nadia; Grange, Dorothy K.; Mendoza-Londono, Roberto; Bradley, Timothy J.; Olney, Ann Haskins; Adès, Lesley; Maher, Joseph F.; Guo, Dongchuan; Buja, L. Maximilian; Kim, Dong; Hyland, James C.; Regalado, Ellen S.

    2011-01-01

    Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut and pulmonary hypertension. PMID:20734336

  10. Contractile properties of isolated vascular smooth muscle after photoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Freas, W.; Hart, J.L.; Golightly, D.; McClure, H.; Muldoon, S.M.

    1989-03-01

    The purpose of this study was to characterize the responses of various types of vascular smooth muscle to conditions that would be encountered during photodynamic therapy, namely laser illumination of photosensitizer-pretreated tissue. Vascular smooth muscle obtained from representative canine, rodent, and rabbit vascular beds was cut into rings and placed in organ baths (37 degrees C, aerated with 95% O2-5% CO2). These vessels were pretreated for 30 min with the photosensitizer hematoporphyrin derivative (HpD, 3-30 micrograms/ml) washed, and then exposed to red laser light (633 nm, 1-3.5 mW) for up to 20 min. Under basal tension conditions laser illumination of HpD-pretreated vessels resulted in an increase in tension, whereas laser illumination of vessels not exposed to HpD did not contract. This sustained contraction was not reversed by washing the tissue with fresh Krebs-Ringer solution. Responses to norepinephrine, transmural electrical stimulation, and elevated concentrations of KCl were reduced in blood vessels tested after HpD laser illumination. Laser-induced contractions of canine carotid arteries did not require the presence of an intact vascular endothelium. Vascular effect of these photosensitizers appears to involve the formation of oxygen-derived radicals. This preparation could provide a good model for examining the effects of free radicals on vascular physiology.

  11. Identification of the smooth muscle excitatory receptors for ergot alkaloids.

    Science.gov (United States)

    Innes, I R

    1962-08-01

    In cats under sodium pentobarbitone anaesthesia the first dose of ergotamine (50 mug/kg) invariably caused retraction of the nictitating membrane and a rise of arterial blood pressure. However, the responses to the dose of ergotamine were strikingly reduced when the cats were previously treated with the adrenaline antagonists phenoxybenzamine (5 mg/kg) or ergotamine (50 mug/kg). Further experiments to identify receptors for ergotamine were carried out on three different isolated smooth muscle preparations: rabbit aorta, rat uterus and dog retractor penis.Receptors for adrenaline were selectively protected by high concentrations of adrenaline throughout exposure of the preparation to a blocking concentration of ergotamine or phenoxybenzamine. Protected muscles responded to ergotamine; unprotected muscles did not. Muscles where receptors for acetylcholine, histamine or 5-hydroxytryptamine were protected by high concentrations of these drugs did not respond to ergotamine. Ergometrine, which has no blocking action on adrenaline receptors, behaved in the same way as ergotamine; muscles which were protected by adrenaline against blockade by phenoxybenzamine responded to ergometrine, but unprotected muscles did not. The stimulant actions of adrenaline, ergotamine and ergometrine were also protected against the blocking action of phenoxybenzamine by treating the muscle with a high concentration of ergometrine instead of adrenaline. It is concluded that, in smooth muscle which can be excited by adrenaline, ergotamine and ergometrine act by combining with adrenaline receptors, and that ergotamine may therefore be regarded not only as an adrenaline antagonist but also as a partial agonist since it excites the same receptors.

  12. Global Strain in Severe Aortic Valve Stenosis

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbæk, Lars; Poulsen, Mikael K

    2012-01-01

    BACKGROUND: -Global longitudinal systolic strain (GLS) is often reduced in aortic stenosis despite normal ejection fraction. The importance of reduced preoperative GLS on long-term outcome after aortic valve replacement (AVR) is unknown. METHODS AND RESULTS: -A total of 125 patients with severe...... aortic stenosis and ejection fraction >40% scheduled for AVR were evaluated preoperatively and divided into 4 groups according to GLS quartiles. Patients were followed up for 4 years. The primary endpoint was major adverse cardiac events (MACE) defined as cardiovascular mortality and cardiac......Score, history with ischemic heart disease and ejection fraction. CONCLUSIONS: -In patients with symptomatic severe aortic stenosis undergoing AVR reduced GLS provides important prognostic information beyond standard risk factors. Clinical Trial Registration-URL: http://www.clinicaltrial.gov. Unique identifier...

  13. Medical image of the week: aortic ring

    Directory of Open Access Journals (Sweden)

    Wong C

    2014-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 78 year old man presented with altered mental status and was found to have an intraventricular hemorrhage. He was intubated for airway protection. On the post-intubation chest radiograph (Figure 1, the patient was noted to have a widening of the right paratracheal stripe. A CT chest (Figure 2 was obtained to characterize this finding and revealed an aortic ring which encircles the trachea and esophagus. Vascular rings are uncommon congenital abnormalities, accounting for approximately 1% of congenital heart disease. Complete vascular rings can occur with a right aortic arch with a ligamentum arteriosum or with a double aortic arch, such as with our patient (1. This ring can cause airway compression, stridor, esophageal compression, or no symptoms at all. As the embryo develops, the left fourth pharyngeal arch normally persists to become the aortic arch while the right fourth pharyngeal arch regresses. If both fourth pharyngeal arches persist, a ...

  14. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    Medline Plus

    Full Text Available Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. ...

  15. Successful Thrombolysis of Aortic Prosthetic Valve Thrombosis ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    Standard surgical treatment using cardiopulmonary bypass carries high maternal and fetal ... 35-year-old female patient presented in the first trimester of pregnancy with PVT at aortic position. .... to a greater risk than thrombolytic therapy does,.

  16. Type B Aortic Dissection: Management Updates

    Directory of Open Access Journals (Sweden)

    Naghmeh Moshtaghi

    2009-12-01

    Full Text Available Acute aortic dissection (AAD is the most frequent catastrophic event of the aorta; it occurs nearly three times as frequently as the rupture of abdominal aortic aneurysm. Sixty percent of dissection cases are classified as proximal or type A and 40% as distal or type B, according to the Stanford Classification. The most frequent causes of death in acute type B dissection are aortic rupture and malperfusion syndrome.We herein review recent data suggesting different management modalities of type B aortic dissection, including medical, surgical, and endovascular treatments. Although medical therapy is still the standard approach in uncomplicated cases, there are subgroups of patients who may benefit from endovascular management. Endovascular techniques or surgery are valuable options for complicated cases. Hybrid suites, multidisciplinary approaches, and good imaging techniques can be considered as the key to success in this regard.

  17. Valve selection in aortic valve endocarditis

    Science.gov (United States)

    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.

  18. Dissecting aortic aneurysm in maintenance hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Ounissi M

    2009-01-01

    Full Text Available The dissecting aortic aneurysm (DAA is a rare pathology that may result in fatal outcome. We report follow up of three cases of DAA patients undergoing maintenance hemo-dialysis who were managed conservatively.

  19. Minimally Invasive Transcatheter Aortic Valve Replacement (TAVR)

    Medline Plus

    Full Text Available Watch a Broward Health surgeon perform a minimally invasive Transcatheter Aortic Valve Replacement (TAVR) Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2017 BroadcastMed, Inc. ...

  20. Microbiological quality of rabbit meat.

    Science.gov (United States)

    Rodríguez-Calleja, Jose M; Santos, Jesús A; Otero, Andrés; García-López, María-Luisa

    2004-05-01

    World rabbit meat production is estimated to be over 1 million tons, and Spain is the third largest producer. Although rabbit meat is marketed and consumed worldwide, information on microbiological quality is very scarce. Here, we report indicator organisms, spoilage flora, sensory quality, and some physicochemical traits of 24 h postmortem chilled rabbit carcasses and prepackaged rabbit meat stored chilled in air for 0 to 3 days at the retail level. The mean total bacterial count (4.01 +/- 0.48 log CFU/g) for carcasses dressed at a small abattoir by a manual process was significantly lower (P Pseudomonas, lactic acid bacteria, and yeasts. These microorganisms and Brochothrix thermosphacta were dominant on carcasses from the large abattoir. On prepacked hind legs (pH 6.26 +/- 0.18) stored at -1 to +1 degree C (supermarket 1), mean aerobic mesophilic count was 5.87 +/- 1.03 log CFU/g, and the major microbial groups were Pseudomonas, yeasts, lactic acid bacteria, and B. thermosphacta. On prepacked whole carcasses (pH 6.37 +/- 0.18) displayed at -1 to +5 degrees C (supermarket 2), mean aerobic mesophilic count was 6.60 +/- 1.18 and the same microbial groups were dominant. Relative Escherichia coli incidence was supermarket 2 > large abattoir > supermarket 1 > small abattoir. Overall, low numbers of coliforms, Enterobacteriaceae, psychrotrophic clostridia, coagulase-positive staphylococci, and molds were found. Sensory scores, pH values, and L-lactic acid content differentiated fresh carcasses from retail samples. Data obtained suggest that the microflora of chilled rabbit meat are different from those found on the meat of other animals.

  1. Maximal right smooth extension chains

    CERN Document Server

    Huang, Yun Bao

    2010-01-01

    If $w=u\\alpha$ for $\\alpha\\in \\Sigma=\\{1,2\\}$ and $u\\in \\Sigma^*$, then $w$ is said to be a \\textit{simple right extension}of $u$ and denoted by $u\\prec w$. Let $k$ be a positive integer and $P^k(\\epsilon)$ denote the set of all $C^\\infty$-words of height $k$. Set $u_{1},\\,u_{2},..., u_{m}\\in P^{k}(\\epsilon)$, if $u_{1}\\prec u_{2}\\prec ...\\prec u_{m}$ and there is no element $v$ of $P^{k}(\\epsilon)$ such that $v\\prec u_{1}\\text{or} u_{m}\\prec v$, then $u_{1}\\prec u_{2}\\prec...\\prec u_{m}$ is said to be a \\textit{maximal right smooth extension (MRSE) chains}of height $k$. In this paper, we show that \\textit{MRSE} chains of height $k$ constitutes a partition of smooth words of height $k$ and give the formula of the number of \\textit{MRSE} chains of height $k$ for each positive integer $k$. Moreover, since there exist the minimal height $h_1$ and maximal height $h_2$ of smooth words of length $n$ for each positive integer $n$, we find that \\textit{MRSE} chains of heights $h_1-1$ and $h_2+1$ are good candidates t...

  2. Effect of age on aortic atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Michael A. Chen; Miwa Kawakubo; Patrick M. Colletti; Dongxiang Xu; Laurie LaBree Dustin; Robert Detrano; Stanley P Azen; Nathan D. Wong; Xue-Qiao Zhao

    2013-01-01

    Objective To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). Methods A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100. Results In this asymptomatic cohort (mean age: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm2 and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification. Conclusions Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.

  3. Complete interruption of the aortic arch

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Hak; Park, In Kyu; Lee, Won Hwa; Kim, Yong Joo; Kang, Duk Sik; Lee, Jong Tae [Kyungpook National University College of Medicine, Taegu (Korea, Republic of)

    1984-09-15

    Complete interrupture of the aortic arch is one of the least common cardiac malformation. In this condition, continuity between the ascending and descending protions of the aorta is not present, and the descending aorta is supplied through a reversing patent ductus arteriosus. In the majority of the patients a ventricular septal defect is present. Authors have experienced a case of the complete interruption of aortic arch, interruption between the left carotid and the left subclavian artery.

  4. Aortic Dissection Cases Presenting with Neurological Deficit

    Directory of Open Access Journals (Sweden)

    Sibel Mumcu

    2014-06-01

    Full Text Available Aortic dissection can be fatal in case of underdiagnosis, and early treatment is essential for the survival. Although acute onset of chest or back pain is most common presenting symptoms, some patients might present with atypical findings such as acute stroke, mesenteric ischaemia, renal failure or myocardial infarction. Here, we report two cases presenting emergency room with atypical findings of aortic dissection which diagnosis is made during etiologic work up for ischemic stroke.

  5. Aortic coarctation repair in the adult.

    Science.gov (United States)

    Cardoso, Goncalo; Abecasis, Miguel; Anjos, Rui; Marques, Marta; Koukoulis, Giovanna; Aguiar, Carlos; Neves, José Pedro

    2014-07-01

    Aortic coarctation can be repaired surgically or percutaneously. The decision should be made according to the anatomy and location of the coarctation, age of the patient, presence of other cardiac lesions, and other anatomic determinants (extensive collaterals or aortic calcification). This article reviews the different therapeutic options available, explaining the differences between children and adults, describing different approaches to the same disease, exemplified by three cases of nonclassic surgical approach and one percutaneous treatment.

  6. Surveillance intervals for small abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Bown, Matthew J; Sweeting, Michael J; Brown, Louise C

    2013-01-01

    Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture.......Small abdominal aortic aneurysms (AAAs [3.0 cm-5.4 cm in diameter]) are monitored by ultrasound surveillance. The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture....

  7. Antithrombotic and Antiatherosclerotic Properties of Olive Oil and Olive Pomace Polar Extracts in Rabbits

    Directory of Open Access Journals (Sweden)

    Nektaria Tsantila

    2007-01-01

    Full Text Available Olive oil polar lipid (OOPL extract has been reported to inhibit atherosclerosis development on rabbits. Olive pomace polar lipid (PPL extract inhibits PAF activity in vitro and the most potent antagonist has been identified as a glycerylether-sn-2-acetyl glycolipid with common structural characteristics with the respective potent antagonist of OOPL. The aim of this study was to investigate the effect of PPL on early atherosclerosis development on rabbits and to compare it with the antiatherosclerotic effect of OOPL. OOPL and PPL inhibition potency, towards both PAF action and PAF binding, was tested in vitro on washed rabbit platelets. Consequently, rabbits were divided into three groups (A, B, and C. All groups were fed atherogenic diet for 22 days. Atherogenic diets in groups B and C were enriched with OOPL and PPL, respectively. At the end of the experimental time, rabbits were euthanized and aortic samples were examined histopathologically. OOPL and PPL inhibited PAF-induced aggregation, as well as specific PAF binding, with PPL being more potent. Free and bound PAF levels and PAF-AH activity were significantly elevated at the end of the experimental time. Plasma total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides levels were also found increased. Groups B and C exhibited significantly increased values of EC50 compared to group A. Histopathological examination revealed that the development of early atherosclerosis lesions in groups B and C were significantly inhibited compared to group A. Significant differences were noted in the early atherosclerosis lesions between groups B and C, thus indicating that PPL exhibit its anti-atherosclerotic activity by blocking PAF receptor. Specific PAF antagonists with similar in vitro and in vivo bioactivity to those that have been previously reported in OOPL exist in PPL.

  8. RPR test for serological survey of rabbit syphilis in companion rabbits.

    Science.gov (United States)

    Saito, Kumiko; Tagawa, Masayo; Hasegawa, Atsuhiko

    2003-07-01

    Since the RPR (rapid plasma regain) test was found to be useful for the diagnosis of rabbit syphilis, serological survey by this test has been carried out in Japanese companion rabbits. A hundred virgin household rabbits kept alone and without signs and history of syphilis were examined by RPR test from April 2001 to March 2002, in Tokyo, Japan. The test was positive in 35 cases and negative in 65 cases. RPR negative rabbits should be selected for breeding to prevent the spread of rabbit syphilis in companion rabbits in Japan.

  9. Pharmacology of airway smooth muscle proliferation

    NARCIS (Netherlands)

    Gosens, Reinoud; Roscioni, Sara S.; Dekkers, Bart G. J.; Pera, Tonio; Schmidt, Martina; Schaafsma, Dedmer; Zaagsma, Johan; Meurs, Herman

    2008-01-01

    Airway smooth muscle thickening is a pathological feature that contributes significantly to airflow limitation and airway hyperresponsiveness in asthma. Ongoing research efforts aimed at identifying the mechanisms responsible for the increased airway smooth muscle mass have indicated that hyperplasi

  10. Minimally invasive "pocket incision" aortic valve surgery.

    Science.gov (United States)

    Yakub, M A; Pau, K K; Awang, Y

    1999-02-01

    A minimally invasive approach to aortic valve surgery through a transverse incision ("pocket incision") at the right second intercostal space was examined. Sixteen patients with a mean age of 30 years underwent this approach. The third costal cartilage was either excised (n = 5) or dislocated (n = 11). The right internal mammary artery was preserved. Cardiopulmonary bypass (CPB) was established with aortic-right atrial cannulation in all except the first case. Aortic valve replacements (AVR) were performed in 15 patients and one had aortic valve repair with concomitant ventricular septal defect closure. There was no mortality and no major complications. The aortic cross-clamp, CPB and operative times were 72 +/- 19 mins, 105 +/- 26 mins and 3 hrs 00 min +/- 29 mins respectively. The mean time to extubation was 5.7 +/- 4.0 hrs, ICU stay of 27 +/- 9 hrs and postoperative hospital stay of 5.1 +/- 1.2 days. Minimally invasive "pocket incision" aortic valve surgery is technically feasible and safe. It has the advantages of central cannulation for CPB, preservation of the internal mammary artery and avoiding sternotomy. This approach is cosmetically acceptable and allows rapid patient recovery.

  11. Retrograde ascending aortic dissection during or after thoracic aortic stent graft placement: insight from the European registry on endovascular aortic repair complications

    DEFF Research Database (Denmark)

    Eggebrecht, Holger; Thompson, Matt; Rousseau, Hervé

    2009-01-01

    BACKGROUND: Single-center reports have identified retrograde ascending aortic dissection (rAAD) as a potentially lethal complication of thoracic endovascular aortic repair (TEVAR). METHODS AND RESULTS: Between 1995 and 2008, 28 centers participating in the European Registry on Endovascular Aortic...

  12. Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study on rabbit aorta.

    Science.gov (United States)

    Togna, G I; Graziani, M; Russo, P; Caprino, L

    2001-08-06

    Effects of cocaine on vascular endothelium relaxing properties and the related mechanism were investigated in vitro in rabbit aorta. Several vasorelaxing agents with different mechanisms, i.e. acetylcholine, substance P, calcium ionophore A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprusside, were employed. Cocaine effects on the vascular response to relaxing agents in cumulative (acetylcholine, substance P, or A23187) or single dose (2,5-di-tert-butyl-hydroquinone) were performed in endothelium-intact aortic rings precontracted with phenylephrine. Relaxing activity of cumulative doses of sodium nitroprusside was evaluated in endothelium-denuded aortic rings, in the presence of cocaine. Cocaine significantly reduced endothelium-dependent relaxations induced by acetylcholine, or substance P. By contrast A23187 endothelium-mediated relaxation as well as endothelium-independent relaxation by sodium nitroprusside were unaffected by cocaine. Furthermore, cocaine significantly increased endothelium-dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic Ca2+-ATPase pump inhibitor, in the aortic rings. These findings indicate that cocaine reduces nitric oxide release from vascular endothelium apparently through the inhibiting action of Ca2+-ATPase pump.

  13. Smooth Optimization Approach for Sparse Covariance Selection

    OpenAIRE

    Lu, Zhaosong

    2009-01-01

    In this paper we first study a smooth optimization approach for solving a class of nonsmooth strictly concave maximization problems whose objective functions admit smooth convex minimization reformulations. In particular, we apply Nesterov's smooth optimization technique [Y.E. Nesterov, Dokl. Akad. Nauk SSSR, 269 (1983), pp. 543--547; Y. E. Nesterov, Math. Programming, 103 (2005), pp. 127--152] to their dual counterparts that are smooth convex problems. It is shown that the resulting approach...

  14. MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors.

    Science.gov (United States)

    Badi, Ileana; Burba, Ilaria; Ruggeri, Clarissa; Zeni, Filippo; Bertolotti, Matteo; Scopece, Alessandro; Pompilio, Giulio; Raucci, Angela

    2015-11-01

    Arterial aging is a major risk factor for the occurrence of cardiovascular diseases. The aged artery is characterized by endothelial dysfunction and vascular smooth muscle cells altered physiology together with low-grade chronic inflammation. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, and endothelial progenitor cell senescence; however, its contribution to aging-associated vascular smooth muscle cells phenotype has not been explored so far. We found that miR-34a was highly expressed in aortas isolated from old mice. Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both endothelial cells and vascular smooth muscle cells. Increased miR-34a as well as decreased SIRT1 expression was also observed in replicative-senescent human aortic smooth muscle cells. miR-34a overexpression in proliferative human aortic smooth muscle cells caused cell cycle arrest along with enhanced p21 protein levels and evidence of cell senescence. Furthermore, miR-34a ectopic expression induced pro-inflammatory senescence-associated secretory phenotype molecules. Finally, SIRT1 protein significantly decreased upon miR-34a overexpression and restoration of its levels rescued miR-34a-dependent human aortic smooth muscle cells senescence, but not senescence-associated secretory phenotype factors upregulation. Taken together, our findings suggest that aging-associated increase of miR-34a expression levels, by promoting vascular smooth muscle cells senescence and inflammation through SIRT1 downregulation and senescence-associated secretory phenotype factors induction, respectively, may lead to arterial dysfunctions.

  15. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP.

    Science.gov (United States)

    Morita, T; Perrella, M A; Lee, M E; Kourembanas, S

    1995-02-28

    Carbon monoxide (CO) is a product of the enzyme heme oxygenase (HO; EC 1.14.99.3). In vascular smooth muscle cells, exogenously administered CO increases cyclic guanosine 3',5'-monophosphate (cGMP), which is an important regulator of vessel tone. We report here that smooth muscle cells produce CO via HO and that it regulates cGMP levels in these cells. Hypoxia, which has profound effects on vessel tone, significantly increased the transcriptional rate of the HO-1 gene resulting in corresponding increases of its mRNA and HO enzymatic activity. In addition, under the same conditions, rat aortic and pulmonary artery smooth muscle cells accumulated high levels of cGMP following a similar time course to that of HO-1 production. The increased accumulation of cGMP in smooth muscle cells required the enzymatic activity of HO, since it was abolished by a specific HO inhibitor, tin protoporphyrin. In contrast, N omega-nitro-L-arginine, a potent inhibitor of nitric oxide (NO) synthesis, had no effect on cGMP produced by smooth muscle cells, indicating that NO is not responsible for the activation of guanylyl cyclase in this setting. Furthermore, conditioned medium from hypoxic smooth muscle cells stimulated cGMP production in recipient cells and this stimulation was completely inhibited by tin protoporphyrin or hemoglobin, an inhibitor of CO production and a scavenger of CO, respectively. This report shows that HO-1 is expressed by vascular smooth muscle cells and that its product, CO, may regulate vascular tone under physiologic and pathophysiologic (such as hypoxic) conditions.

  16. Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Tattevin, P; Basuino, L; Bauer, D; Diep, B A; Chambers, H F

    2010-02-01

    Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (Pceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (Pceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

  17. A SAS IML Macro for Loglinear Smoothing

    Science.gov (United States)

    Moses, Tim; von Davier, Alina

    2011-01-01

    Polynomial loglinear models for one-, two-, and higher-way contingency tables have important applications to measurement and assessment. They are essentially regarded as a smoothing technique, which is commonly referred to as loglinear smoothing. A SAS IML (SAS Institute, 2002a) macro was created to implement loglinear smoothing according to…

  18. Aortic annulus and ascending aorta: Comparison of preoperative and periooperative measurement in patients with aortic stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Smid, Michal [Cardiology Department of Internal Medicine, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: kosvin@seznam.cz; Ferda, Jiri [Department of Radiology, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: ferda@fnplzen.cz; Baxa, Jan [Department of Radiology, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: baxaj@fnplzen.cz; Cech, Jakub [Cardiology Department of Internal Medicine, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: cechj@fnplzen.cz; Hajek, Tomas [Department of Cardiac Surgery, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: hajekt@fnplzen.cz; Kreuzberg, Boris [Department of Radiology, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: kreuzberg@fnplzen.cz; Rokyta, Richard [Cardiology Department of Internal Medicine, School of Medicine Plzen, Charles University Prague and University Hospital Plzen, alej Svobody 80, 304 60 Plzen (Czech Republic)], E-mail: rokyta@fnplzen.cz

    2010-04-15

    Background: Precise determination of the aortic annulus size constitutes an integral part of the preoperative evaluation prior to aortic valve replacement. It enables the estimation of the size of prosthesis to be implanted. Knowledge of the size of the ascending aorta is required in the preoperative analysis and monitoring of its dilation enables the precise timing of the operation. Our goal was to compare the precision of measurement of the aortic annulus and ascending aorta using magnetic resonance (MR), multidetector-row computed tomography (MDCT), transthoracic echocardiography (TTE), and transoesophageal echocardiography (TEE) in patients with degenerative aortic stenosis. Methods and results: A total of 15 patients scheduled to have aortic valve replacement were enrolled into this prospective study. TTE was performed in all patients and was supplemented with TEE, CT and MR in the majority of patients. The values obtained were compared with perioperative measurements. For the measurement of aortic annulus, MR was found to be the most precise technique, followed by MDCT, TTE, and TEE. For the measurement of ascending aorta, MR again was found to be the most precise technique, followed by MDCT, TEE, and TTE. Conclusion: In our study, magnetic resonance was found to be the most precise technique for the measurement of aortic annulus and ascending aorta in patients with severe degenerative aortic stenosis.

  19. Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in Bicuspid Aortic Valve Stenosis

    DEFF Research Database (Denmark)

    Yoon, Sung-Han; Lefèvre, Thierry; Ahn, Jung-Ming

    2016-01-01

    BACKGROUND: Few studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices. OBJECTIVE...

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

    OpenAIRE

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

    2015-01-01

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