Endothelial responses to mechanical stress: Where is the mechanosensor?

Objective: The endothelium is normally subjected to mechanical deformation resulting from shear stress and from strain associated with stretch of the vessel wall. These stimuli are detected by a mechanosensor that initiates a variety of signaling systems responsible for triggering the functional responses. The identity of the mechanosensor has not been established. This article discusses the different mechanisms of mechanosensing that have been proposed and reviews the literature with respect to signaling systems that are activated in response to stress and strain in endothelium. Data Sources: Published literature related to mechanotransduction, signal transduction pathways initiated by strain in endothelium, and pathophysiologic effects of abnormal shear forces in diseases. Data Extraction and Synthesis: Proposed mechanisms of mechanosensing include stretch-sensitive ion channels, protein kinases associated with the cytoskeleton, integrin-cytoskeletal interactions, cytoskeletal-nuclear interactions, and oxidase systems capable of generating reactive oxygen species. However, the molecular identity of the mechanosensor is not known, nor is it clear whether multiple sensing mechanisms exist. Conclusions: Many responses are initiated in cells subjected to mechanical deformation, including alterations in ion channel conductance, activation of signal transduction pathways, and altered expression of specific genes. Future progress in this field will require a critical distinction between cell systems that become activated during mechanical strain and the identity of the cellular mechanosensor that triggers subsequent responses.