How do endothelial cells respond to forces from blood flow at the molecular level?

Molecular determinants in endothelial Shc required for flow-mediated physiological and pathological responses

Endothelial cells line the inside surface of blood vessels. They are constantly exposed to shear stress – the friction generated by blood flowing across the surface of the cells. Endothelial cells respond to changes in shear stress and trigger biological processes which can be healthy (physiological) or contribute to disease (pathological). Collateral arteries provide additional vessels for when tissues require increased blood supply, such as during exercise. Alternative routes are also needed in case of a blockage, such as during a heart attack or stroke. Shear stress influences the growth of collateral vessels (a physiological process). In areas of disturbed blood flow, shear stress influences the development of atherosclerosis – where arteries become clogged up with fatty deposits (a pathological process). Dr Ellie Tzima has previously shown that an important protein called Shc is involved in both remodelling of collateral arteries and atherosclerosis. Now Dr Tzima will lead a team to study the precise molecular role of Shc in remodelling following shear stress in genetically-modified mice. This research could drive new treatments to prevent atherosclerosis and to improve the blood supply to tissue following a blockage.