Plasma membrane-mediated mechanosensing in vascular endothelial cells

抄録

Vascular endothelial cells (ECs) play critical roles in regulating a variety of vascular functions, including maintenance of the vascular tone, blood coagulation and fibrinolysis, and provision of selective permeability to proteins. It has recently become apparent that ECs show alterations in their morphology, functions and gene expression profile in response to exposure to hemodynamic forces, namely, shear stress and stretch. These responses also play important roles in maintaining normal circulatory system functions and homeostasis, whereas their impairment leads to various vascular diseases, including hypertension, aneurysm and atherosclerosis. The mechanisms underlying the mechanotransduction, however, are not yet clearly understood. Plasma membranes of the ECs have recently been shown to respond differently to shear stress and stretch, by rapidly changing their lipid order, membrane fluidity, and cholesterol content. Artificial lipid-bilayer membranes also show similar changes of the lipid order in response to exposure to shear stress and stretch, indicating that these are physical phenomena rather than biological reactions. Such physical changes then activate the membrane receptors and cell responses specific to each type of force. These findings suggest that the plasma membranes of ECs act as mechanosensors, and in response to mechanical forces, they show alterations of their physical properties, with modification of the conformation and functions of the membrane proteins, which then trigger activation of the downstream signaling pathways.