Disturbed Flow Induces Atherosclerosis by Annexin A2-Mediated Integrin Activation
Catherine Demos, Darian Williams, Hanjoong Jo
Abstract
therosclerosis is a chronic inflammatory disease, occurring preferentially in branches and curves in arteries exposed to disturbed blood flow (d-flow). In contrast, straight arteries are exposed to stable flow (s-flow) and are protected from atherosclerosis development. 1-3 D-flow is characterized by low, oscillatory shear stress (OS) whereas s-flow is associated with unidirectional (either pulsatile or nonpulsatile) and relatively high level of laminar shear stress. Flow regulates these atherogenic responses by regulating gene expression and signaling pathways in endothelial cells (ECs). Mechanosensors (also known as mechanoreceptors) detect changes in shear stress direction and magnitude with respect to time in ECs. Once detected, the mechanosensors convert the mechanical force into biochemical signals, triggering cell signaling pathways, and changes in cell functions. D-flow induces, while s-flow prevents, endothelial dysfunction including inflammation, endothelial-mesenchymal transition, thrombosis, vasoconstriction, and barrier dysfunction, which in turn lead to atherosclerosis in conjunction with additional risk factors such as hypercholesterolemia. Are there specialized mechanosensors that detect d-flow versus s-flow, or does one mechanosensor respond differently to different flow conditions? In the current edition of Circulation Research, Zhang et al define a novel molecular mechanism by which d-flow induces inflammation and atherosclerosis by activating integrin 5 through interaction with ANXA2 (annexin A2) by a Piezo1-dependent mechanism.