Mechanotransduction in endothelial responses to shear stress: review of work in Dr. Chien's laboratory

Shear stresses play an important role in vascular biology in health and disease. While disturbed flows with low shear stresses in the bends and bifurcations of the arterial tree are atherogenic, laminar flows with high shear stresses in the straight part of the vessel is atheroresistant. Thus, elucidation of the mechanotransduction mechanism in vascular endothelial cells in response to shear stress has become an important research topic among bioengineers and vascular biologists. Here is a summary of studies performed in Dr. Shu Chien's laboratory on shear stress-induced signal transduction and gene expression during the period from 1992-1999. These studies, together with efforts from other research groups, demonstrate that integrins, which are transmembrane molecules that interact with both extracellular matrices and intracellular cytoskeleton and kinases in the focal adhesions, are important in mechanotransduction. This hypothesis is mainly supported by the similarity between cellular and molecular events elicited by shear stress and those activated during the integrin-mediated cell attachment to extracellular matrices. Evidence is also provided to show that the dynamic and specific interaction between integrin and extracellular matrices is essential for mechanotransduction.