Abstract
Physiological levels of laminar shear stress completely abrogate apoptosis of human endothelial cells in response to a variety of stimuli and might therefore importantly contribute to endothelial integrity. We show here that the apoptosis-suppressive effects of shear stress are mediated by upregulation of Cu/Zn SOD and NO synthase. Shear stress-mediated inhibition of endothelial cell apoptosis in response to exogenous oxygen radicals, oxidized LDL, and tumor necrosis factor-alpha was associated with complete inhibition of caspase-3-like activity, the central effector arm executing the apoptotic cell death program in endothelial cells. Shear stress-dependent upregulation of Cu/Zn SOD and NO synthase blocks activation of the caspase cascade in response to apoptosis-inducing stimuli. These findings establish the upregulation of Cu/Zn SOD and NO synthase by shear stress as a central protective cellular mechanism to preserve the integrity of the endothelium after proapoptotic stimulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antisense Elements (Genetics)
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Apoptosis / drug effects
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Apoptosis / physiology*
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Caspase 3
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Caspases / metabolism
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Cells, Cultured
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DNA Fragmentation
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology*
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Gene Expression Regulation, Enzymologic
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Humans
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Lipoproteins, LDL / pharmacology
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / metabolism*
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Oxidative Stress / physiology
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Stress, Mechanical
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism*
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Superoxides / pharmacology
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
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Umbilical Veins / cytology
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Umbilical Veins / enzymology
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Xanthine Oxidase / genetics
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Xanthine Oxidase / metabolism
Substances
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Antisense Elements (Genetics)
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Lipoproteins, LDL
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Tumor Necrosis Factor-alpha
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oxidized low density lipoprotein
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Superoxides
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Nitric Oxide Synthase
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Superoxide Dismutase
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Xanthine Oxidase
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CASP3 protein, human
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Caspase 3
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Caspases