title: Estrogen receptor alpha supports cardiomyocytes indirectly through post-infarct cardiac c-kit+ cells.
abstract: Despite previous studies demonstrating a cardioprotective role of estradiol via its estrogen receptor (ER)alpha, the underlying mechanisms remain unclear. Here we aimed to define ERalpha-involved mechanisms against cardiac injury. Seven days after myocardial infarction in male rats, cardiac ERalpha was upregulated in post-infarct cardiac c-kit+ cells accumulating in periinfarct myocardium as shown by Western blotting and immunofluorescence staining. Further, we isolated post-infarct cardiac c-kit+ cell population by modified magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS), and confirmed predominant ERalpha expression in this post-infarct cardiac c-kit+ cell population by real-time PCR. These post-infarct cardiac c-kit+ cells, characterized by upregulated transcription factors implicated in cardiogenic differentiation (GATA-4, Notch-2) and genes required for self-renewal (Tbx3, Akt), maintained a stable phenotype in vitro for more than 3 months. ERalpha stimulation supported proliferation but prevented differentiation of undifferentiated myoblast cells. When adult myocytes isolated from infarcted rat hearts were co-cultured with post-infarct cardiac c-kit+ cells, ERalpha stimulation inhibited apoptosis and enhanced survival of these myocytes. These findings suggest that cardiac ERalpha supports survival of cardiomyocytes through post-infarct cardiac c-kit+ cells, which may contribute to cardioprotection against cardiac injury.
authors.affiliation: Center for Cardiovascular Research (CCR) and Institute of Pharmacology, Charité - Universitätsmedizin Berlin, Hessische Str. 3-4, 10115 Berlin, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Brinckmann
authors.forename: Elena
authors.initials: E
authors.lastname: Kaschina
authors.forename: Wassim
authors.initials: W
authors.lastname: Altarche-Xifró
authors.forename: Caterina
authors.initials: C
authors.lastname: Curato
authors.forename: Melanie
authors.initials: M
authors.lastname: Timm
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Grzesiak
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Jun
authors.initials: J
authors.lastname: Li