Endothelial Phenotypes in Atherosusceptible Regions In Vivo Endothelial Phenotypes in Native Atherosusceptible Regions

The interactions of blood flow with complex vessel geometry generate hemodynamic characteristics, including the heterogeneous spatial and temporal mechanical forces acting on the vessel wall. Vascular endothelial cells (ECs) covering the inner surface of blood vessels are constantly exposed to shear stress because of the frictional force created by the blood flow. ECs respond to the changes of local shear stress to modulate intracellular signaling, which leads to alterations of gene expression, cell morphology, and structural remodeling. The correlation of atheroma location and site-specific endothelial dysfunctional phenotype with the nonlaminar characteristics of blood flow and shear stress at curved regions, branch points, and bifurcations indicates that such disturbed flow patterns are atheroprone. At these atheroprone regions, the flow departs from pulsatile, unidirectional shear stress to create flow-separation zones that include flow reversal, oscillating shear stress, and occasional turbulence. In contrast, the shear stress in the straight atheroresistant part of the arteries is pulsatile and has well-defined directions. The shear stresses resulting from different flow patterns initiate differential steps of signaling events in the endothelium, including mechanosensing, intracellular transmission of stress, conversion of mechanical force to biochemical signals, and feedback mechanisms. As a result, the endothelium develops different adaptive phenotypes to differentially react with other coexistent risk factors, such as high cholesterol, hypertension, obesity, diabetes mellitus, and smoking, to contribute to the site-specific susceptibility for the initiation and progression of atherosclerosis. The aim of this review is to provide a brief summary of the current knowledge with a focus on the shear stress–initiated signaling and its regulation of endothelial function and dysfunction, as well as the communication between ECs and other vascular cells. The pathological implications in atherosclerosis and future perspectives are also discussed. The effects of fluid shear stress on endothelial gene expression and the functional consequences have been previously reviewed in depth.