[HTML][HTML] Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

B Zhou, LB Honor, H He, Q Ma, JH Oh… - The Journal of …, 2011 - Am Soc Clin Investig
B Zhou, LB Honor, H He, Q Ma, JH Oh, C Butterfield, RZ Lin, JM Melero-Martin, E Dolmatova
The Journal of clinical investigation, 2011Am Soc Clin Investig
The epicardium makes essential cellular and paracrine contributions to the growth of the
fetal myocardium and the formation of the coronary vasculature. However, whether the
epicardium has similar roles postnatally in the normal and injured heart remains enigmatic.
Here, we have investigated this question using genetic fate-mapping approaches in mice. In
uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased
epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs) …
The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection.
The Journal of Clinical Investigation