title: Adult mouse epicardium modulates myocardial injury by secreting paracrine factors.
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.
authors.affiliation: Department of Cardiology, Children’s Hospital Boston, Boston, Massachusetts, USA. zhoubin@sibs.ac.cn
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Leah B
authors.initials: LB
authors.lastname: Honor
authors.forename: Huamei
authors.initials: H
authors.lastname: He
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Oh
authors.forename: Catherine
authors.initials: C
authors.lastname: Butterfield
authors.forename: Ruei-Zeng
authors.initials: RZ
authors.lastname: Lin
authors.forename: Juan M
authors.initials: JM
authors.lastname: Melero-Martin
authors.forename: Elena
authors.initials: E
authors.lastname: Dolmatova
authors.forename: Heather S
authors.initials: HS
authors.lastname: Duffy
authors.forename: Alexander von
authors.initials: Av
authors.lastname: Gise
authors.forename: Pingzhu
authors.initials: P
authors.lastname: Zhou
authors.forename: Yong Wu
authors.initials: YW
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Lianchun
authors.initials: L
authors.lastname: Wang
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hall
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006335:Heart Injuries / Q000378:metabolism; D006706:Homeostasis; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010496:Pericardium / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D036341:Intercellular Signaling Peptides and Proteins