Laminar Shear Stress

TLDR

Mechanical forces modulate cellular function in many tissues, especially in the cardiovascular system, where the endothelium rapidly and sensitively responds to the mechanical conditions created by blood flow and the cardiac cycle. The study investigates whether steady laminar shear stress stimulates cellular responses essential for endothelial function and atheroprotection. Shear stress modulates atherogenesis by altering endothelial coagulation, leukocyte migration, smooth muscle growth, lipoprotein uptake, and survival, and the authors propose a signal transduction model involving mechanotransducers, intermediate signaling molecules, MAPKs, and effector molecules such as nitric oxide. The endothelial response to shear stress may explain how risk factors like hypertension, diabetes, hypercholesterolemia, and sedentary lifestyle promote atherosclerosis.

Abstract

Abstract —Mechanical forces are important modulators of cellular function in many tissues and are particularly important in the cardiovascular system. The endothelium, by virtue of its unique location in the vessel wall, responds rapidly and sensitively to the mechanical conditions created by blood flow and the cardiac cycle. In this study, we examine data which suggest that steady laminar shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. We explore the ability of shear stress to modulate atherogenesis via its effects on endothelial-mediated alterations in coagulation, leukocyte and monocyte migration, smooth muscle growth, lipoprotein uptake and metabolism, and endothelial cell survival. We also propose a model of signal transduction for the endothelial cell response to shear stress including possible mechanotransducers (integrins, caveolae, ion channels, and G proteins), intermediate signaling molecules (c-Src, ras, Raf, protein kinase C) and the mitogen activated protein kinases (ERK1/2, JNK, p38, BMK-1), and effector molecules (nitric oxide). The endothelial cell response to shear stress may also provide a mechanism by which risk factors such as hypertension, diabetes, hypercholesterolemia, and sedentary lifestyle act to promote atherosclerosis.