ERβ (oestrogen receptor β) activation has been shown to be cardioprotective, but the cell types and mechanisms involved are not understood. To investigate whether ERβ restricted to cardiomyocytes contributes to the observed cardioprotection, we tested the effects of cardiomyocyte-specific ERβ-OE (ERβ overexpression) on survival, cardiac remodelling and function after MI (myocardial infarction) and studied the molecular pathways potentially involved. Female and male mice with cardiomyocyte-specific ERβ-OE and WT (wild-type) littermates were subjected to chronic anterior coronary artery ligation or sham surgery. Two weeks after MI, ERβ-OE mice showed improved survival (100% and 83% compared with 76% and 58% in WT females and males respectively). ERβ-OE was associated with attenuated LV (left ventricular) 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 ERβ-mediated myocardial protection. First, male and female ERβ-OE mice had a lower reduction of SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) expression after MI, suggesting less reduction in diastolic Ca2+-reuptake into the sarcoplasmic reticulum post-MI. Secondly, male ERβ-OE revealed attenuated cardiac fibrosis in the remote LV tissue and expression of fibrosis markers collagen I and III, periostin and miR-21. Cardiomyocyte-specific ERβ-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.
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March 2016
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Cover Image
Cover Image
Image of immunofluroscence staining of mouse gonads (left – testis and right – ovary) attached to the mesonephros from between embryonic day 12 and 13. Green indicates the sertoli cell protein Anti-Mullerain Hormone (AMH) and red indicates the ovarian protein called Foxl2. Blue indicates DAPI (which stains the nucleus). The antibodies are AMH (MIS) E19 santa Cruz, sc-34833 and Foxl2 Novus NB100-1277. For further details please see pp. 421-432. The image was kindly generated and provided by I. Knarston, K. Ayers and A. Sinclair.
Research Article|
January 26 2016
Cardiomyocyte-specific overexpression of oestrogen receptor β improves survival and cardiac function after myocardial infarction in female and male mice
Iris Schuster;
Iris Schuster
1
*EA 2992, Medical University of Nîmes-Montpellier, Centre Hospitalo-Universitaire de Nîmes, Nîmes, France
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Shokoufeh Mahmoodzadeh;
Shokoufeh Mahmoodzadeh
1
†Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
‡DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
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Elke Dworatzek;
Elke Dworatzek
1
‡DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
§Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany
Correspondence: Dr Elke Dworatzek (email [email protected]).
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Frédéric Jaisser;
Frédéric Jaisser
║Inserm, U872, Paris, France
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Smail Messaoudi;
Smail Messaoudi
║Inserm, U872, Paris, France
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Ingo Morano;
Ingo Morano
†Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Vera Regitz-Zagrosek
Vera Regitz-Zagrosek
‡DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
§Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany
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Publisher: Portland Press Ltd
Received:
August 28 2015
Revision Received:
November 16 2015
Accepted:
November 25 2015
Accepted Manuscript online:
November 25 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (5): 365–376.
Article history
Received:
August 28 2015
Revision Received:
November 16 2015
Accepted:
November 25 2015
Accepted Manuscript online:
November 25 2015
Citation
Iris Schuster, Shokoufeh Mahmoodzadeh, Elke Dworatzek, Frédéric Jaisser, Smail Messaoudi, Ingo Morano, Vera Regitz-Zagrosek; Cardiomyocyte-specific overexpression of oestrogen receptor β improves survival and cardiac function after myocardial infarction in female and male mice. Clin Sci (Lond) 1 March 2016; 130 (5): 365–376. doi: https://doi.org/10.1042/CS20150609
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