Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Circ Cardiovasc Interv. 2012 Aug 1;5(4):605-14. doi: 10.1161/CIRCINTERVENTIONS.112.971028.
Acquired aortic valve disease and valvular calcification is highly prevalent in adult populations worldwide and is associated with significant cardiovascular morbidity and mortality. At present, there are no medical therapies that will prevent or regress aortic valve calcification or stenosis and surgical or transcatheter aortic valve replacement remain the only effective therapies for treating this disease. In the setting of valve injury as a result of exposure to biochemical mediators or hemodynamic forces, normal homeostatic processes are disrupted resulting in extracellular matrix degradation, aberrant matrix deposition and fibrosis, inflammatory cell infiltration, lipid accumulation, and neoangiogenesis of the valve tissue and, ultimately, calcification of the valve. Calcification of the aortic valve is now understood to be an active process that involves the coordinated actions of resident valve endothelial and interstitial cells, circulating inflammatory and immune cells, and bone marrow-derived cells. These cells may undergo a phenotype transition to become osteoblast-like cells and elaborate bone matrix, endothelial-to-mesenchymal transition, and form matrix vesicles that serve as a nidus for microcalcifications. Each of these mechanisms has been shown to contribute to aortic valve calcification suggesting that strategies that target these cellular events may lead to novel therapeutic interventions to halt the progression or reverse aortic valve calcification.
在全球范围内，成人人群中普遍存在获得性主动脉瓣疾病和瓣钙化，这与重大心血管发病率和死亡率相关。目前，尚无预防或逆转主动脉瓣钙化或狭窄的医学治疗方法，手术或经导管主动脉瓣置换仍然是治疗这种疾病的唯一有效疗法。在由于暴露于生化介质或血流动力而导致瓣膜损伤的情况下，正常的动态平衡过程被破坏，导致细胞外基质降解、基质异常沉积和纤维化、炎症细胞浸润、脂质积累以及瓣组织的新生血管形成，最终导致瓣钙化。现在已经了解到主动脉瓣钙化是一个涉及常驻瓣膜内皮和间质细胞、循环炎症和免疫细胞以及骨髓来源细胞的协调作用的主动过程。这些细胞可能经历表型转变成为成骨样细胞并产生骨基质、内皮细胞向间充质转化，并形成基质小泡，作为微钙化的核心。这些机制中的每一种都已被证明有助于主动脉瓣钙化，这表明针对这些细胞事件的策略可能会导致新的治疗干预措施来阻止主动脉瓣钙化的进展或逆转。
