Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:656-664
© 1999 American Heart Association, Inc.
Original Contributions |
Upregulation of Superoxide Dismutase and Nitric Oxide Synthase Mediates the Apoptosis-Suppressive Effects of Shear Stress on Endothelial Cells
From the Department of Internal Medicine IV, Division of Cardiology (S.D., C.H., A.M.Z.), University of Frankfurt; and the Department of Nephrology (J.G.), University of Würzburg, Germany.
Correspondence to Andreas M Zeiher, MD, Department of Internal Medicine IV, Division of Cardiology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Zeiher{at}em.uni-frankfurt.de
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-
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.
Key Words: oxidative stress • cell death • hemodynamic • atherosclerosis • antioxidant
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