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Cardiomyocyte-specific overexpression of estrogen receptor beta improves survival and cardiac function after myocardial infarction in female and male mice

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Item Type:Article
Title:Cardiomyocyte-specific overexpression of estrogen receptor beta improves survival and cardiac function after myocardial infarction in female and male mice
Creators Name:Schuster, I. and Mahmoodzadeh, S. and Dworatzek, E. and Jaisser, F. and Messaoudi, S. and Morano, I. and Regitz-Zagrosek, V.
Abstract:BACKGROUND: Estrogen receptor beta (ERbeta) activation has been shown to be cardioprotective, but the involved cell types and mechanisms are not understood. To investigate whether ERbeta restricted to cardiomyocytes contributes to observed cardioprotection, we tested the effects of a cardiomyocyte-specific ERbeta overexpression (ERbeta-OE) on survival, cardiac remodelling and function after myocardial infarction (MI) and studied potentially involved molecular pathways. METHODS AND RESULTS: Female and male mice with cardiomyocyte-specific ERbeta-OE and wild type (WT) littermates were subjected to chronic anterior coronary artery ligation or sham surgery. Two weeks after MI, ERbeta-OE mice showed improved survival (100 and 83% vs 76 and 58% in WT females and males respectively). ERbeta-OE was associated with attenuated left ventricular (LV) dilatation, smaller increase in heart weight, less lung congestion at similar MI size, and improved systolic and diastolic function in both sexes. We identified two potential pathways for ERbeta mediated myocardial protection. First, male and female ERbeta-OE mice had a lower reduction of SERCA2a expression after MI, suggesting less reduction in diastolic Ca2+-reuptake into sarcoplasmic reticulum post MI. Second, male ERbeta-OE revealed attenuated cardiac fibrosis in the remote LV tissue and expression of fibrosis markers Col I, Col III, periostin, and miR21. CONCLUSIONS: Cardiomyocyte-specific ERbeta-OE improved survival associated with reduced maladaptive remodelling, improved cardiac function and less heart failure development after MI in both sexes. These effects seem to be related, at least in part, to a better maintenance of Ca2+-cycling in both sexes and a lower induction of cardiac fibrosis in males after MI.
Keywords:Cardiac Function, Fibrosis, Myocardial Infarction, Oestrogen Receptor beta, Sex Differences, Animals, Mice
Source:Clinical Science
ISSN:0143-5221
Publisher:Portland Press (U.K.)
Volume:130
Number:5
Page Range:365-376
Date:26 January 2016
Official Publication:https://doi.org/10.1042/CS20150609
PubMed:View item in PubMed

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