Di Fusco Stefania Angela, Borrelli Nunzia, Poli Stefano, Bernelli Chiara, Perone Francesco, Aquilani Stefano, Maggioni Aldo Pietro, Di Pasquale Giuseppe, Gabrielli Domenico, Oliva Fabrizio, Colivicchi Furio
U.O.C. Cardiologia Clinica e Riabilitativa, Presidio Ospedaliero San Filippo Neri - ASL Roma 1, Roma.
Unità di Malattie Cardiologiche Congenite in Età Adulta, AORN dei Colli - Ospedale Monaldi, Napoli.
G Ital Cardiol (Rome). 2023 Apr;24(4):293-304. doi: 10.1714/4004.39820.
Degenerative calcific aortic valve stenosis (CAVS) is a chronic disease whose prevalence has increased over the last decade because of the aging of the general population. CAVS pathogenesis is characterized by complex molecular and cellular mechanisms that promote valve fibro-calcific remodeling. During the first phase, referred to as initiation, the valve undergoes collagen deposition and lipid and immune cell infiltration due to mechanical stress. Subsequently, during the progression phase, the aortic valve undergoes chronic remodeling through osteogenic and myofibroblastic differentiation of interstitial cells and matrix calcification. Knowledge of the mechanisms underlying CAVS development supports the resort to potential therapeutic strategies that interfere with fibro-calcific progression. Currently, no medical therapy has demonstrated the ability to significantly prevent CAVS development or slow its progression. The only treatment available in symptomatic severe stenosis is surgical or percutaneous aortic valve replacement. The aim of this review is to highlight the pathophysiological mechanisms involved in CAVS pathogenesis and progression and to discuss potential pharmacological treatments able to inhibit the main pathophysiological mechanisms of CAVS, including lipid-lowering treatment with lipoprotein(a) as emergent therapeutic target.
退行性钙化性主动脉瓣狭窄（CAVS）是一种慢性疾病，在过去十年中，由于普通人群的老龄化，其患病率有所上升。CAVS的发病机制具有促进瓣膜纤维钙化重塑的复杂分子和细胞机制。在第一阶段，即起始阶段，由于机械应力，瓣膜会发生胶原蛋白沉积以及脂质和免疫细胞浸润。随后，在进展阶段，主动脉瓣通过间质细胞的成骨和成肌纤维细胞分化以及基质钙化而经历慢性重塑。了解CAVS发展的潜在机制有助于采取干预纤维钙化进展的潜在治疗策略。目前，尚无药物治疗能够显著预防CAVS的发展或减缓其进展。有症状的重度狭窄的唯一可用治疗方法是外科手术或经皮主动脉瓣置换术。本综述的目的是强调CAVS发病机制和进展中涉及的病理生理机制，并讨论能够抑制CAVS主要病理生理机制的潜在药物治疗方法，包括以脂蛋白(a)作为紧急治疗靶点的降脂治疗。
