Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954124 | Journal of Molecular and Cellular Cardiology | 2009 | 10 Pages |
Abstract
Despite previous studies demonstrating a cardioprotective role of estradiol via its estrogen receptor (ER)α, the underlying mechanisms remain unclear. Here we aimed to define ERα-involved mechanisms against cardiac injury. Seven days after myocardial infarction in male rats, cardiac ERα 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 ERα 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. ERα 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, ERα stimulation inhibited apoptosis and enhanced survival of these myocytes. These findings suggest that cardiac ERα supports survival of cardiomyocytes through post-infarct cardiac c-kit+ cells, which may contribute to cardioprotection against cardiac injury.
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Authors
Marie Brinckmann, Elena Kaschina, Wassim Altarche-Xifró, Caterina Curato, Melanie Timm, Aleksandra Grzesiak, Jun Dong, Kai Kappert, Ulrich Kintscher, Thomas Unger, Jun Li,