Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Ann N Y Acad Sci. 2010 Feb;1188:177-83. doi: 10.1111/j.1749-6632.2009.05098.x.
In this chapter, we review the working hypothesis that the roots of adult valvular heart disease (VHD) lie in embryonic development. Valvulogenesis is a complex process in which growth factors signal the process of endocardium-to-mesenchyme transformation (EMT) resulting in formation of prevalvular "cushions." The post-EMT processes, whereby cushions are morphogenetically remolded into valve leaflets, are less well understood, but they require periostin. Mice with targeted deletion of periostin develop degenerative changes similar to human forms of VHD. Mitral valves are also abnormally elongated in hypertrophic cardiomyopathy (HCM), which plays an important role in clinical disease expression. However, the mechanism for this is unclear, but correlates with enhanced expression of periostin in a specific population of ventricular cells derived from the embryonic proepicardial organ, which accumulate at sites where valvular endocardial EMT is reactivated. Collectively, these findings suggest that developmental mechanisms underlie adult valve responses to genetic mutations in degenerative VHD and HCM.
在本章中，我们回顾了一个工作假说，即成人心脏瓣膜病（VHD）的根源在于胚胎发育。瓣膜发生是一个复杂的过程，其中生长因子发出信号，启动心内膜向间质转化（EMT）的过程，导致前瓣膜“垫”的形成。形成瓣膜小叶的 EMT 后过程理解得还不够，但需要骨桥蛋白。靶向敲除骨桥蛋白的小鼠会出现退行性变化，类似于人类 VHD 形式。肥厚型心肌病（HCM）也会导致二尖瓣异常伸长，在临床疾病表现中起着重要作用。然而，其机制尚不清楚，但与特定人群的心室细胞中骨桥蛋白的表达增强相关，这些细胞来自胚胎的心包原基，在心包原基重新激活瓣膜心内膜 EMT 的部位聚集。总的来说，这些发现表明，发育机制是导致成人瓣膜对退行性 VHD 和 HCM 中基因突变的反应的基础。
