Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
Circ Res. 2011 May 27;108(11):1392-412. doi: 10.1161/CIRCRESAHA.110.234138.
Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, nonosseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High-resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research.
钙化性主动脉瓣狭窄（CAVS）是老龄化社会面临的主要健康问题。在人类组织中鉴定出成骨样细胞和破骨样细胞，这导致该领域发生了重大范式转变。CAVS 曾被认为是一种被动的、退行性过程，而现在认为 CAVS 中的钙化进展是受到主动调控的。通过开发 CAVS 的小鼠模型，对异位成骨、非骨组织钙化和异位成骨样细胞（其功能似乎与骨骼成骨细胞不同）对瓣膜功能障碍的贡献的机制研究得到了促进。最近的研究还表明，瓣膜纤维化以及钙化可能在限制瓣叶运动方面发挥重要作用，因此 CAVS 可能更恰当地被视为一种纤维-钙化性疾病。高分辨率超声心动图和磁共振成像已成为测试药物和基因干预体内疗效的有用工具。本文回顾了在人类和动物中的关键研究，这些研究塑造了 CAVS 领域的当前范式，并为未来的研究提出了有希望的领域。
