ROLE OF MECHANICAL FORCES IN ENDOTHELIAL HOMEOSTASIS

摘要

Shear stress and stretch can modulate functions of vascular endothelial cells (ECs) by activating mechano-sensors, signaling pathways, and gene/protein expressions. Sustained shear stress with a forward direction causes only a transient activation of atherogenic genes, followed by down-regulation. In ECs exposed to complex flow with little forward direction, activation of these atherogenic genes is sustained, and cell turnover is accelerated. Cyclic uniaxial stretch causes orientation of actin stress fibers perpendicular to stretch direction, and this causes a decrease of intracellular stress, transient JNK activation, and protection of ECs against apoptosis. Cyclic biaxial stretch without a preferred direction has opposite effects. In the straight arteries, laminar shear stress with a forward direction and uniaxial strain with a circumferential direction have anti-atherogenic effects. At branch points, the complex shear flow and mechanical strain with little net direction are atherogenic. The direction of mechanical forces has important effects on ECs in health and disease.