Mechanisms involved in calcific aortic valve disease. An endothelial injury or dysfunction causes increased expression of adhesion molecules, such as VCAM-1, ICAM-1, and E-selectin. Inflammatory cells such as T lymphocytes and monocytes are recruited, and they release cytokines and proteolytic enzymes, which stimulates the activation and differentiation of resident fibroblasts or quiescent valvular interstitial cells (qVICs) into myofibroblasts (activated VICs, aVICs) and osteoblastic VICs (obVICs) with consequent calcification. VICs also undergo apoptosis, and the formation of apoptotic vesicles contributes to calcification. Circulating lipids also enter the valvular interstitial tissue and undergo oxidative modification; the oxidized lipoproteins (oxLDL) are highly cytotoxic and stimulate inflammatory activity and mineralization.