Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, New York 10461; email:
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 China.
Annu Rev Physiol. 2017 Feb 10;79:21-41. doi: 10.1146/annurev-physiol-022516-034001. Epub 2016 Dec 9.
Normal aortic valves are composed of valve endothelial cells (VECs) and valve interstitial cells (VICs). VICs are the major cell population and have distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between the VECs and VICs plays critical roles in aortic valve morphogenesis. Disruption of major cell signaling pathways results in aortic valve malformations, including bicuspid aortic valve (BAV). BAV is a common congenital heart valve disease that may lead to calcific aortic valve disease (CAVD), but there is currently no effective medical treatment for this beyond surgical replacement. Mouse and human studies have identified causative gene mutations for BAV and CAVD via disrupted VEC to VIC signaling. Future studies on the developmental signaling mechanisms underlying aortic valve malformations and the pathogenesis of CAVD using genetically modified mouse models and patient-induced pluripotent stem cells may identify new effective therapeutic targets for the disease.
正常的主动脉瓣由瓣内皮细胞(VECs)和瓣间质细胞(VICs)组成。VICs 是主要的细胞群体，在心内膜和心脏神经嵴细胞中有明显的胚胎起源。VECs 和 VICs 之间的细胞信号转导在主动脉瓣形态发生中起着关键作用。主要细胞信号通路的破坏导致主动脉瓣畸形，包括二叶主动脉瓣(BAV)。BAV 是一种常见的先天性心脏瓣膜疾病，可能导致钙化性主动脉瓣疾病(CAVD)，但目前除了手术置换外，对此病尚无有效的治疗方法。通过破坏 VEC 到 VIC 的信号转导，小鼠和人类研究已经确定了 BAV 和 CAVD 的致病基因突变。使用基因修饰小鼠模型和患者诱导多能干细胞研究主动脉瓣畸形发育信号机制和 CAVD 的发病机制，可能为该疾病确定新的有效治疗靶点。
