NFAT signalling and the differentiation of coronary smooth muscle cells

Abstract

Development of the heart is complex and cells with different embryonic origins participate in cardiac organogenesis. The first and second heart fields deliver cells to generate the atrial and ventricular chambers and also participate in venous inflow and arterial outflow tract formation. There are also important cellular contributions from two extra-cardiac cell populations, i.e. cardiac neural crest cells and the pro-epicardium.1 The neural crest cells populate the outflow tract, are involved in septation of the arterial pole into the aorta and pulmonary trunk, and contribute to the smooth muscle layer of these large vessels. The pro-epicardium forms at the venous pole of the heart as a cauliflower-like cluster, which establishes contact to the myocardial surface and through proliferation and migration rapidly invest the myocardium to establish the epicardium. The embryonic epicardium gives rise to epicardium-derived cells (EPDCs) that undergo epithelial mesenchymal transformation (EMT) and migrate into the myocardial wall to participate in coronary artery formation and to differentiate into interstitial and perivascular fibroblasts ( Figure 1 ).4 Figure 1 Model of coronary smooth muscle differentiation by calcineurin/NFAT signalling. The adult myocardium consists of three tissue layers, i.e. the endocardium, myocardium, and epicardium. In the embryo, cells from the epicardium undergo EMT and form a migratory cell population, which has been termed epicardium-derived cells (EPDC). These cells will migrate into the subepicardium or into the ventricular wall and give rise to interstitial or adventitial fibroblasts and smooth muscle cells of the coronary arteries, while their contribution to the coronary endothelium is uncertain. The epicardium secretes signals (IGF2, PDGF), which stimulate myocardial proliferation resulting in chamber wall expansion, whereas the …