Cardiac repair by epicardial EMT: Current targets and a potential role for the primary cilium

Despite therapeutic advances that have prolonged life, myocardial infarction (MI) remains a leading cause of death worldwide and imparts a significant economic burden. The advancement of treatments to improve cardiac repair post-MI requires the discovery of new targeted treatment strategies. Recent studies have highlighted the importance of the epicardial covering of the heart in both cardiac development and lower vertebrate cardiac regeneration. The epicardium serves as a source of cardiac cells including smooth muscle cells, endothelial cells and cardiac fibroblasts. Mammalian adult epicardial cells are typically quiescent. However, the fetal genetic program is reactivated post-MI, and epicardial epithelial-to-mesenchymal transition (EMT) occurs as an inherent mechanism to support neovascularization and cardiac healing. Unfortunately, endogenous EMT is not enough to encourage sufficient repair. Recent developments in our understanding of the mechanisms supporting the EMT process has led to a number of studies directed at augmenting epicardial EMT post-MI. With a focus on the role of the primary cilium, this review outlines the newly demonstrated mechanisms supporting EMT, the role of epicardial EMT in cardiac development, and promising advances in augmenting epicardial EMT as potential therapeutics to support cardiac repair post-MI.