Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4- and TGF-β1-Dependent Pathway

Inflammation and calcification are common features of aortic valve (AV) diseases [1]. AV diseases preferentially occur in the aortic side of the valvular leaflets where they are exposed to complex and unstable hemodynamic conditions [2]. The reasons for this side-specific response, potentially associated with the local shear stress environment, are not completely understood. In addition, while it has been shown that exposure of vascular endothelial cells to oscillatory shear stress induces inflammatory responses by bone morphogenic protein (BMP)-4-dependent mechanisms [3], it is not clear whether BMP plays a role in the inflammation of AV leaflet exposed to altered mechanical environment. In the present study, we hypothesized that AV inflammation occurs preferentially in the aortic surface of AV leaflets in a BMP and TGF-β1-dependent manner due to the local hemodynamic loading conditions. This hypothesis was tested via three sets of experiments focused on the biological response of porcine AV leaflets using either a standard or pro-osteogenic medium.