Cardiovascular disease: A turbulent path to plaque formation.

Abstract

Plaque deposits often occur in curved arterial regions with turbulent blood flow. Endothelial cells have been found to respond to blood flow through a previously unidentified signalling pathway that affects plaque build-up. See Letter p.579 YAP and TAZ, effectors of the Hippo signalling pathway, have previously been reported to be sensors for mechanical stimuli. Now Yu Huang and colleagues show that these molecules sense mechanical forces generated by blood flow and play a role in atherosclerosis pathogenesis. Atherosclerotic plaques form in regions of disturbed blood flow. The authors show that disturbed flow increases YAP/TAZ activity and increases expression of proinflammatory genes, whereas steady unidirectional shear flow inhibits YAP/TAZ activity through integrin activation. The authors show that in mice, endothelial cell-specific knockdown of YAP retards atherosclerotic plaque formation. This work points to the integrin–Gα13–RhoA–YAP pathway as a possible target against atherosclerosis.