Cardiac Development and Congenital Heart Disease
Coronary vasculature formation coincides with the envelopment of the epicardium over the heart. The epicardium provides paracrine cues supporting the formation of the primitive coronary plexus. Following epithelial-to-mesenchymal transformation (EMT), epicardial cells differentiate into non-myocyte lineages (fibroblasts and vascular mural cells) and provide instructive cues for arterio-venous specification of endothelial cells; a process that is dysregulated upon disruption of epicardial EMT.
The adult heart is unable to regenerate lost myocardium and vascular structures after myocardial infarction (MI). Although the epicardium is reactivated and produces pro-angiogenic cues following MI, this response is inefficient in the prevention of maladaptive cardiac remodeling. Adeno-associated virus (AAV) technology provides a therapeutic strategy to restore the expression of angiogenic factors and stimulate angiogenesis in the heart after ischemic injury.