The arterial epicardium: A developmental approach to cardiac disease and repair

Abstract

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 aneurysmformation 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.