Overview of the main mechanisms leading to valvular remodelling. Among the main mechanisms involved in AV remodelling, shear stress can induce endothelial damage and TGF-β accumulation within the valvular tissue. TGF-β promotes the EndMT of VECs as well as the transformation of qVICs into myofibroblast-activated VICs (aVICs), which can secrete collagen and promote valvular fibrosis and thickening. VECs dysfunction favours the infiltration of oxidized LDL and inflammatory cells, including macrophages, thereby promoting foam cell formation and initiating a process that resembles vascular atherosclerosis. Macrophage secretion of TNF-α and IL-1β promotes the deactivation of aVICs. Subsequent exposure to IL-6 promotes their osteogenic transition towards obVICs capable of promoting the mineralization process. αSMA, α-smooth muscle actin; MФ, macrophage; oxLDL, oxidized LDL; ALP: alkaline phosphatase.