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Aortic valve stenosis (AS) is characterized by fibrosis and calcification of valves leading to aortic valve narrowing, resulting in high wall shear stress across the valves. We previously demonstrated that high shear stress can activate platelet-derived transforming growth factor-β1 (TGF-β1), a cytokine that induces fibrosis and calcification. The aim of this study was to investigate the role of shear-induced platelet release of TGF-β1 and its activation in AS.

We studied hypercholesterolemic Ldlr^−/−Apob^100/100/Mttp^fl/fl/Mx1Cre^+/+ (Reversa) mice that develop AS on Western diet and a surgical ascending aortic constriction mouse model that acutely simulates the hemodynamics of AS to study shear-induced platelet TGF-β1 release and activation. Reversa mice on Western diet for 6 months had thickening of the aortic valves, increased wall shear stress, and increased plasma TGF-β1 levels …