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J Clin Invest. 2011 May;121(5):1894-904. doi: 10.1172/JCI45529. Epub 2011 Apr 18.

Adult mouse epicardium modulates myocardial injury by secreting paracrine factors.

Author information

1
Department of Cardiology, Children’s Hospital Boston, Boston, Massachusetts, USA. zhoubin@sibs.ac.cn

Abstract

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.

PMID:
21505261
PMCID:
PMC3083761
DOI:
10.1172/JCI45529
[Indexed for MEDLINE]
Free PMC Article

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