Center for Cardiovascular Research, The Research Institute at Nationwide Children's Hospital, 575 Children's Drive, WB4239, Columbus, OH, 43215, USA.
The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
Curr Cardiol Rep. 2018 Mar 8;20(4):21. doi: 10.1007/s11886-018-0968-9.
This review aims to highlight the past and more current literature related to the multifaceted pathogenic programs that contribute to calcific aortic valve disease (CAVD) with a focus on the contribution of developmental programs.
Calcification of the aortic valve is an active process characterized by calcific nodule formation on the aortic surface leading to a less supple and more stiffened cusp, thereby limiting movement and causing clinical stenosis. The mechanisms underlying these pathogenic changes are largely unknown, but emerging studies have suggested that signaling pathways common to valvulogenesis and bone development play significant roles and include Transforming Growth Factor-β (TGF-β), bone morphogenetic protein (BMP), Wnt, Notch, and Sox9. This comprehensive review of the literature highlights the complex nature of CAVD but concurrently identifies key regulators that can be targeted in the development of mechanistic-based therapies beyond surgical intervention to improve patient outcome.
本篇综述旨在强调过去和当前更多的与钙化性主动脉瓣疾病(CAVD)相关的多方面致病机制的文献,重点介绍发育相关机制在其中的作用。
主动脉瓣钙化是一个主动的过程,其特征是在主动脉表面形成钙化结节,导致瓣叶较不柔韧且更僵硬,从而限制运动并导致临床狭窄。这些致病变化的机制在很大程度上尚不清楚,但新兴的研究表明,参与瓣膜发生和骨发育的信号通路起着重要作用,包括转化生长因子-β(TGF-β)、骨形态发生蛋白(BMP)、Wnt、Notch 和 Sox9。对文献的全面综述强调了 CAVD 的复杂性,但同时确定了关键的调节剂,这些调节剂可作为超越手术干预的机械治疗的靶点,以改善患者的预后。