Endothelial mechanosensors of shear stress as regulators of atherogenesis.

PURPOSE OF REVIEW

Differences in local blood flow patterns along the endothelium may trigger abnormal vascular responses which can have profound pathophysiological consequences. While endothelial cells exposed to laminar blood flow (high shear stress) are protected from atherosclerosis formation, turbulent or disturbed blood flow, which occurs at bends and bifurcations of blood vessels, facilitates atherosclerosis formation. Here, we will highlight the endothelial cell mechanisms involved in detecting shear stress and their translation into downstream biochemical signals.

RECENT FINDINGS

Prior evidence supports a role for integrins as mechanotransducers in the endothelium by promoting phosphorylation of different targets through the activation of focal adhesion kinase. Our recent findings show that integrins contact integrin-linked kinase and regulate vasomotor responses by an endothelial nitric oxide synthase-dependent mechanism, which stabilizes the production of vasoactive factor nitric oxide. In addition, different structures of endothelial cells, mainly primary cilia, are investigated, as they can explain the differential responses to laminar versus disturbed flow.

SUMMARY

The discovery of a connection between endothelial cell structures such as cilia, integrin, extracellular matrix, and signaling events opens today a new chapter in our understanding of the molecular mechanisms regulating vascular responses to the changes in flow.