Role of Reduced Endothelial Shear Stress in the Development of Atherosclerosis

Abstract

Atherosclerosis is a chronic, inflammatory, fibroproliferative disease primarily of large- and medium-sized conduit arteries. Although the entire vasculature is exposed to the atherogenic effects of the systemic risk factors, atherosclerotic
lesions form at specific regions of the arterial tree, such as in the vicinity of branch points, the outer wall of bifurcations,
and the inner wall of curvatures, where disturbed flow with low endothelial shear stress occurs. Vascular endothelial
cells (ECs), uniquely situated at the interface between the blood and the vascular wall, are constantly exposed to fluid
shear stress. Shear stress is reduced (<5 dynes/cm2
) at the outer walls of a bifurcation, branching, inner curvature walls,
and these are the sites susceptible to atherosclerosis, the sites where atherosclerotic plaques are predominantly located. Physiological levels of laminar shear stress modulate cellular signaling and ECs function and are protective against
atherogenesis. ECs are effective biological mechanotransducers which convert physical stimuli of shear forces to intracellular biochemical signals that provide normal vascular function and atheroprotection.Low endothelial shear stress
attenuates nitric oxide (NO)-dependent atheroprotection; promotes low-density lipoprotein cholesterol (LDL) uptake,
synthesis, and permeability; it promotes oxidative stress and inflammation, as well as vascular smooth muscle cell
(VSMC) migration, differentiation, and proliferation; it attenuatesdegradation of extracellular matrix (ECM) in vascular
wall, and plays potential role in atherosclerotic plaque neovascularization; low endothelial shear stress increases plaque
calcification and thrombogenecity. The present article reviews the mechanisms of abovementioned changes in vascular
walls caused by low endothelial shear stress.