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  Vol. 282 No. 21, December 1, 1999 TABLE OF CONTENTS
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Hemodynamic Shear Stress and Its Role in Atherosclerosis

Adel M. Malek, MD, PhD; Seth L. Alper, MD, PhD; Seigo Izumo, MD

JAMA. 1999;282:2035-2042.

Atherosclerosis, the leading cause of death in the developed world and nearly the leading cause in the developing world, is associated with systemic risk factors including hypertension, smoking, hyperlipidemia, and diabetes mellitus, among others. Nonetheless, atherosclerosis remains a geometrically focal disease, preferentially affecting the outer edges of vessel bifurcations. In these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothelial cell surface as a result of blood flow, is weaker than in protected regions. Studies have identified hemodynamic shear stress as an important determinant of endothelial function and phenotype. Arterial-level shear stress (>15 dyne/cm2) induces endothelial quiescence and an atheroprotective gene expression profile, while low shear stress (<4 dyne/cm2), which is prevalent at atherosclerosis-prone sites, stimulates an atherogenic phenotype. The functional regulation of the endothelium by local hemodynamic shear stress provides a model for understanding the focal propensity of atherosclerosis in the setting of systemic factors and may help guide future therapeutic strategies.


Author Affiliations: Neurosurgery, Brigham and Women's Hospital and Children's Hospital (Dr Malek), and Departments of Neurosurgery (Dr Malek), Medicine (Drs Alper and Izumo), and Cell Biology (Dr Alper), Harvard Medical School, and Molecular Medicine and Renal Units (Dr Alper), and Cardiovascular Division (Dr Izumo), Beth Israel Deaconess Medical Center, Boston, Mass; and Division of Interventional Neurovascular Radiology, University of California at San Francisco, San Francisco (Dr Malek).


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