Exposure to Shear Stress Alters Endothelial Adhesiveness

Tsao, Philip S.; Lewis, Neil P.; Alpert, Susan; Cooke, John P.

doi:10.1161/01.cir.92.12.3513

Cited by 153 publications

(85 citation statements)

References 33 publications

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“…24,25 Perfusion of vein with either the nonselective potassium channel blocker TEA or the K ATP channel blocker glibenclamide did not alter the downregulation of thrombomodulin in response to arterial flow conditions (Table 1). A role for calcium in transducing signals from increased shear stress also should be considered because the application of shear stress to cultured endothelial cells increases intracellular calcium concentrations.…”

Section: Discussionmentioning

confidence: 98%

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

et al. 1999

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Background —The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. Methods and Results —Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, ≈200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9±4.8% and 41.0±3.0% CD31, respectively; P <0.01) and by Western blotting (1.35±0.20 and 0.15±0.03 ratio of von Willebrand factor, respectively; P <0.01). The ability of endothelial cells to generate activated protein C also decreased from 62±14 to 19±10 ng · min −1 · 1000 cells −1 ( P =0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd 3+ , to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0±0.4% to 8.5±0.7% CD31 ( P <0.02). Conclusions —In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.

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Section: Discussionmentioning

confidence: 98%

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

et al. 1999

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“…31 Aji and colleagues 9 recently reported that oral L-arginine for 6 months prevented xanthoma development and inhibited atherosclerosis in LDL cholesterol receptor knockout mice, suggesting that this response may be mediated by NO. Moreover, long-term administration of supplementary dietary arginine markedly inhibits intimal lesion formation in hypercholesterolemic rabbits 32 and preserves endothelium-dependent vasodilatation.…”

Section: Discussionmentioning

confidence: 99%

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans

1999

Journal of Cardiothoracic and Vascular Anesthesia

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Background-Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of L-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease. Methods and Results-Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly randomized to either oral L-arginine or placebo, 3 g TID. Endothelium-dependent coronary blood flow reserve to acetylcholine (10 Ϫ6 to 10 Ϫ4 mol/L) was assessed at baseline and after 6 months of therapy. There was no difference between the two study groups in clinical characteristics or in the coronary blood flow in the response to acetylcholine at baseline. After 6 months, the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group (149Ϯ20% versus 6Ϯ9%, PϽ0.05). This was associated with a decrease in plasma endothelin concentrations and an improvement in patients' symptoms scores in the L-arginine treatment group compared with the placebo group. Conclusions-Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations. This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease. (Circulation. 1998;97:2123-2128.)

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“…Nitric oxide (NO) is generated by endothelial nitric oxide synthase (eNOS), and has an important function in the regulation of vascular tone by inhibiting vascular smooth muscle contraction and affecting endothelial-leukocyte interaction by inhibiting platelet aggregation and leukocyte adhesion to the endothelium. 2,3 Hepatic blood flow usually is under the control of eNOS, which is present in sinusoidal endothelial cells. 4 Endothelial cell injury and dysfunction usually develop after transplant.…”

Section: Introductionmentioning

confidence: 99%

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Azarpira

Namazi²,

Malahi³

et al. 2016

Exp Clin Transplant

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Objectives: Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. Materials and Methods:We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Results: Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Conclusions: Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

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Exposure to Shear Stress Alters Endothelial Adhesiveness

Cited by 153 publications

References 33 publications

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans

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