Department of Cardiology, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA.
Circ Res. 2012 Jun 8;110(12):1628-45. doi: 10.1161/CIRCRESAHA.111.259960.
Epithelial to mesenchymal transition (EMT) converts epithelial cells to mobile and developmentally plastic mesenchymal cells. All cells in the heart arise from one or more EMTs. Endocardial and epicardial EMTs produce most of the noncardiomyocyte lineages of the mature heart. Endocardial EMT generates valve progenitor cells and is necessary for formation of the cardiac valves and for complete cardiac septation. Epicardial EMT is required for myocardial growth and coronary vessel formation, and it generates cardiac fibroblasts, vascular smooth muscle cells, a subset of coronary endothelial cells, and possibly a subset of cardiomyocytes. Emerging studies suggest that these developmental mechanisms are redeployed in adult heart valve disease, in cardiac fibrosis, and in myocardial responses to ischemic injury. Redirection and amplification of disease-related EMTs offer potential new therapeutic strategies and approaches for treatment of heart disease. Here, we review the role and molecular regulation of endocardial and epicardial EMT in fetal heart development, and we summarize key literature implicating reactivation of endocardial and epicardial EMT in adult heart disease.
上皮-间充质转化（EMT）将上皮细胞转化为具有移动性和发育可塑性的间充质细胞。心脏中的所有细胞都来源于一个或多个 EMT。心内膜和心外膜 EMT 产生成熟心脏中大多数非心肌细胞谱系。心内膜 EMT 产生瓣膜祖细胞，对于心脏瓣膜的形成和完全心脏分隔是必需的。心外膜 EMT 对于心肌生长和冠状动脉形成是必需的，并且它产生心脏成纤维细胞、血管平滑肌细胞、一部分冠状动脉内皮细胞，并且可能还有一部分心肌细胞。新出现的研究表明，这些发育机制在成人心脏瓣膜病、心脏纤维化以及心肌对缺血性损伤的反应中被重新利用。疾病相关 EMT 的重定向和放大为心脏病的治疗提供了潜在的新的治疗策略和方法。在这里，我们回顾了心内膜和心外膜 EMT 在胎儿心脏发育中的作用和分子调控，并总结了关键文献，这些文献表明心内膜和心外膜 EMT 在成人心脏病中的重新激活。
