Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease.
Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease.
复制标题
DOI：
10.1161/circresaha.111.259960
复制
发表时间：
2012-06-08
影响因子：
20.1
通讯作者：
Pu WT
中科院分区：
文献类型：
--
作者：
von Gise A;Pu WT
上皮细胞向间充质细胞转化（EMT）将上皮细胞转化为移动的和发育可塑性的间充质细胞。心脏中的所有细胞都来自一个或多个EMT。在发育中的心脏内，内膜和心外膜EMT产生成熟心脏的大部分非心肌细胞谱系。内皮细胞EMT产生瓣膜祖细胞，并且是形成心脏瓣膜和完全心脏分隔所必需的。心外膜EMT是心肌生长和冠状动脉血管形成所需的，并产生心脏成纤维细胞、血管平滑肌细胞、冠状动脉内皮细胞的子集以及可能的心肌细胞的子集。新兴的研究表明，这些发展机制是重新部署在成人心脏瓣膜疾病，心脏纤维化，心肌缺血性损伤的反应。疾病相关EMT的重定向和扩增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，我们审查的作用和分子调控的内皮细胞和心外膜EMT在胎儿心脏发育，我们总结的关键文献涉及再激活的内皮细胞和心外膜EMT在成人心脏病。
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. Within the developing heart, endocardial and epicardial EMTs produce most of the non-cardiomyocyte 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 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.