Endothelial shear stress responses: mechanotransduction, cell stress and adaptation

Abstract

Endothelial cells lining the walls of blood vessels are one of the most important regulatory elements of the circulatory system. These mechanosensitive cells are in a direct contact with the flow of blood and able to detect deformation through its tangential component (shear) and the component directed along the normal to the surface (tension). Shear stress is the key inducer of the complex of signaling pathways mediated by tyrosine kinases, integrins, ion channels, involving also membrane lipids, glycocalyx and other cellular components. There are large amount of data on signal transduction in the literature, but less attention is paid to cellular adaptation to shear stress and there is relatively little information on the involvement of stress response genes in that process. Hydrodynamic conditions in certain zones of the vascular system are characterized by considerable heterogeneity, which can lead to weakening of feedbacks necessary for maintaining homeostasis in endothelial cells. This can contribute to the development of diseases such as atherosclerosis. This review presents new aspects and concepts related to the responses of endotheliocytes to shear stress and, in addition, highlights the basic methods of analyzing the effects of shear stress in vitro. Purpose of the study. Generalization of modern data on mechanisms of mechanosensitivity and mechanotransduction of the endothelium. Results. The review outlines the main mechanosensitivity mechanisms of endothelial cells, the pathways of intracellular signaling, the involvement of mechanisms of cellular stress response and adaptation. There are descriptions of experiments in which the molecular basis of mechanotransduction is identified, including the determination of proteins and other molecules involved in detection, signal transduction, and cellular response to shear stress.