title: Erythropoietin responsive cardiomyogenic cells contribute to heart repair post myocardial infarction.
abstract: The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function.
authors.affiliation: Institute of Pharmacology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany.
authors.forename: Maria Patapia
authors.initials: MP
authors.lastname: Zafiriou
authors.forename: Claudia
authors.initials: C
authors.lastname: Noack
authors.forename: Bernhard
authors.initials: B
authors.lastname: Unsöld
authors.forename: Michael
authors.initials: M
authors.lastname: Didie
authors.forename: Elena
authors.initials: E
authors.lastname: Pavlova
authors.forename: Henrike J
authors.initials: HJ
authors.lastname: Fischer
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Martin W
authors.initials: MW
authors.lastname: Bergmann
authors.forename: Ali
authors.initials: A
authors.lastname: El-Armouche
authors.forename: Wolfram-Hubertus
authors.initials: WH
authors.lastname: Zimmermann
authors.forename: Laura Cecilia
authors.initials: LC
authors.lastname: Zelarayan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin
keywords: Epo-responsive MHC expressing cells; Erythropoietin; Erythropoietin responsive myosin heavy chain expressing cells; Ischemia; Myocardial regeneration