Gittenberger-de Groot Adriana C., Winter E. M., Goumans M. J., Bartelings M. M., Poelmann R. E.
Departments Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands
The significance of the epicardium that covers the heart and the roots of the great arteries should not be underestimated as it is a major component with impact on development, disease, and repair. The epicardium differentiates from the proepicardial organ located at the venous pole (vPEO). The differentiation capacities of the vPEO into epicardium-derived cells (EPDCs) have been extensively described. A hitherto escaped part of the epicardium derives from a second proepicardial organ located at the arterial pole (aPEO) and covers the intrapericardial part of the aorta and pulmonary trunk. In avian and mouse embryos, disturbance of epicardium differentiation causes a spectrum of cardiac anomalies including coronary artery abnormalities, deficient annulus fibrosis with rhythm disturbances, valve malformations, and non-compaction cardiomyopathies. Late in prenatal life the epicardium becomes dormant, losing the activity of many genes. In human cardiac diseases, both arterial and venous epicardium can be activated again into EPDCs. The epicardial reactivation observed after experimental myocardial infarction and during aneurysm formation of the ascending aorta provides clinical relevance. EPDCs applied for cell therapy demonstrate repair processes synergistic with the resident cardiac progenitor stem cells that probably share an embryonic origin with EPDCs. Future therapeutic strategies might be possible addressing cell autonomous-based and signaling capacities of the adult epicardium.
覆盖心脏和大动脉根部的心外膜的重要性不应被低估，因为它是一个对发育、疾病和修复有影响的主要组成部分。心外膜由位于静脉极的前心外膜器官（vPEO）分化而来。vPEO向心外膜衍生细胞（EPDC）的分化能力已被广泛描述。心外膜的一个迄今未被关注的部分来自位于动脉极的第二个前心外膜器官（aPEO），并覆盖主动脉和肺动脉干的心包内部分。在鸟类和小鼠胚胎中，心外膜分化的紊乱会导致一系列心脏异常，包括冠状动脉异常、伴有节律紊乱的纤维环缺陷、瓣膜畸形和心肌致密化不全。在产前后期，心外膜进入休眠状态，许多基因失去活性。在人类心脏疾病中，动脉和静脉心外膜都可以再次被激活成为EPDC。在实验性心肌梗死后和升主动脉瘤形成过程中观察到的心外膜重新激活具有临床意义。用于细胞治疗的EPDC显示出与驻留心脏祖干细胞协同的修复过程，这些祖干细胞可能与EPDC有共同的胚胎起源。未来的治疗策略可能针对成年心外膜基于细胞自主性和信号传导的能力。
