Cardiovascular Development Group, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaén, 23071 Jaén, Spain.
Medina Foundation, Technology Park of Health Sciences, 18016 Granada, Spain.
Int J Mol Sci. 2022 Mar 16;23(6):3220. doi: 10.3390/ijms23063220.
The epicardium is the outermost cell layer in the vertebrate heart that originates during development from mesothelial precursors located in the proepicardium and septum transversum. The epicardial layer plays a key role during cardiogenesis since a subset of epicardial-derived cells (EPDCs) undergo an epithelial-mesenchymal transition (EMT); migrate into the myocardium; and differentiate into distinct cell types, such as coronary vascular smooth muscle cells, cardiac fibroblasts, endothelial cells, and presumably a subpopulation of cardiomyocytes, thus contributing to complete heart formation. Furthermore, the epicardium is a source of paracrine factors that support cardiac growth at the last stages of cardiogenesis. Although several lineage trace studies have provided some evidence about epicardial cell fate determination, the molecular mechanisms underlying epicardial cell heterogeneity remain not fully understood. Interestingly, seminal works during the last decade have pointed out that the adult epicardium is reactivated after heart damage, re-expressing some embryonic genes and contributing to cardiac remodeling. Therefore, the epicardium has been proposed as a potential target in the treatment of cardiovascular disease. In this review, we summarize the previous knowledge regarding the regulation of epicardial cell contribution during development and the control of epicardial reactivation in cardiac repair after damage.
心外膜是脊椎动物心脏的最外层细胞层，在胚胎发育过程中起源于位于心外膜前体细胞和横隔中的间皮前体。心外膜层在心脏发生过程中起着关键作用，因为一部分心外膜来源的细胞（EPDCs）经历上皮-间充质转化（EMT）；迁移到心肌中；并分化为不同的细胞类型，如冠状动脉平滑肌细胞、心肌成纤维细胞、内皮细胞，以及可能的一部分心肌细胞，从而有助于心脏的完全形成。此外，心外膜是旁分泌因子的来源，可以在心脏发生的最后阶段支持心脏生长。尽管有几项谱系追踪研究提供了一些关于心外膜细胞命运决定的证据，但心外膜细胞异质性的分子机制仍不完全清楚。有趣的是，过去十年的一些开创性工作指出，心脏损伤后成年心外膜被重新激活，重新表达一些胚胎基因，并有助于心脏重构。因此，心外膜已被提议作为心血管疾病治疗的潜在靶点。在这篇综述中，我们总结了以前关于发育过程中心外膜细胞贡献的调节以及心脏损伤后修复中心外膜重新激活的控制的知识。
