Hemodynamic Shear Stress and Its Role in Atherosclerosis

TLDR

Atherosclerosis, the leading cause of death worldwide, is a geometrically focal disease that preferentially affects the outer edges of vessel bifurcations where reduced hemodynamic shear stress—an important determinant of endothelial function—contributes to endothelial dysfunction in the presence of systemic risk factors such as hypertension, smoking, hyperlipidemia, and diabetes. The study proposes that local hemodynamic shear stress regulates endothelial function and thereby explains the focal propensity of atherosclerosis, offering a model to guide future therapeutic strategies. High arterial shear stress (>15 dyne/cm²) induces endothelial quiescence and atheroprotective gene expression, whereas low shear stress (<4 dyne/cm²) prevalent at atherosclerosis‑prone sites promotes an atherogenic phenotype.

Abstract

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.