FIGURE 2.

The effect of high shear stress on circulating cells and their role in promoting valvular inflammation. (A) Acceleration of blood velocity through the narrowed aortic valve exposes circulating cells to high shear stress (HSS) and creates turbulent flow vortices on the aortic side of the aortic valve leaflets. (B) HSS induces increased expression of monocyte adhesion molecule Mac1 mediated by increased expression and activation of Piezo1. (C) TNF α released by tissue macrophages, TGFβ released by HSS-activated platelets, and NETosis of shear activated neutrophils promote myofibroblastic differentiation of aortic valve interstitial cells (VICs). Increased magnitude oscillatory shear stress (OSS) promotes End-MT and impaired protective NO signalling (End-MT, endothelial-mesenchymal transition; Mac1, macrophage-1 antigen; TGF-β1, transforming growth factor β1; TNF-α, tumour necrosis factor-alpha; NET, neutrophil extracellular trap; NO, nitric oxide).