Blood-flow-mediated mechanotransduction in vascular endothelial cells

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Endothelial cells(ECs)sense shear stress and transduce blood flow infbrmation into functionalresponses that play important roles in vascular homeostasis and pathophysiology. A unique feature ofshear-stress-sensing is the involvement of many different types of membrane-bound molecules, but themechanisms remain unknown. Shear stress evokes a rapid, dose-dependent increase in intracellular Ca2+concentration caused by an influx of extracellular Ca2+via ATP-operated P2×4 ion channels activatedby endogenous ArP released by ECs. To analyze the dynamics of ArP release, we visualized ArP at thecell surface. When exposed to shear stress, ECs simultaneously released ArP at caveolae. Immediatelyafter the ArP release, Ca2+wave occurred at the same site as the ArP release. Caveolar membranefluidity increased over the entire EC membranes in response to shear stress. These findings indicate thatEC membranes directly respond to shear stress and that these changes link to shear-stress-mechanotranuction mechnisms.