Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

Bin Zhou, Leah B. Honor, Huamei He, Ma Qing, Jin Hee Oh, Catherine Butterfield, Ruei Zeng Lin, Juan M. Melero-Martin, Elena Dolmatova, Heather S. Duffy, Alexander Von Gise, Pingzhu Zhou, Yong Wu Hu, Gang Wang, Bing Zhang, Lianchun Wang, Jennifer L. Hall, Marsha A. Moses, Francis X. McGowan, William T. Pu

Research output: Contribution to journalArticle

314 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1894-1904
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number5
DOIs
StatePublished - May 2 2011

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    Zhou, B., Honor, L. B., He, H., Qing, M., Oh, J. H., Butterfield, C., Lin, R. Z., Melero-Martin, J. M., Dolmatova, E., Duffy, H. S., Von Gise, A., Zhou, P., Hu, Y. W., Wang, G., Zhang, B., Wang, L., Hall, J. L., Moses, M. A., McGowan, F. X., & Pu, W. T. (2011). Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. Journal of Clinical Investigation, 121(5), 1894-1904. https://doi.org/10.1172/JCI45529