title: Cardiomyocyte-specific overexpression of oestrogen receptor β improves survival and cardiac function after myocardial infarction in female and male mice.
abstract: 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 Ca(2+)-ATPase 2a) expression after MI, suggesting less reduction in diastolic Ca(2+)-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 Ca(2+) cycling in both sexes and a lower induction of cardiac fibrosis in males after MI.
authors.affiliation: EA 2992, Medical University of Nîmes-Montpellier, Centre Hospitalo-Universitaire de Nîmes, Nîmes, France.
authors.forename: Iris
authors.initials: I
authors.lastname: Schuster
authors.affiliation: Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Mahmoodzadeh
authors.affiliation: 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 Elke.Dworatzek@charite.de.
authors.forename: Elke
authors.initials: E
authors.lastname: Dworatzek
authors.affiliation: Inserm, U872, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jaisser
authors.affiliation: Inserm, U872, Paris, France.
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
authors.affiliation: Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Morano
authors.affiliation: 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.
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D047629:Estrogen Receptor beta / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005355:Fibrosis; D008297:Male; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D012737:Sex Factors; D013599:Systole / Q000502:physiology; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D015415:Biomarkers; D047629:Estrogen Receptor beta; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: cardiac function; fibrosis; myocardial infarction; oestrogen receptor β; sex differences