{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:11:07Z","timestamp":1789819867496,"version":"4.0.1"},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:p>ER\u03b2 (oestrogen receptor \u03b2) activation has been shown to be cardioprotective, but the cell types\u00a0and mechanisms involved are not understood. To investigate whether ER\u03b2 restricted to cardiomyocytes contributes to the observed cardioprotection, we tested the effects of cardiomyocyte-specific ER\u03b2-OE (ER\u03b2 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 ER\u03b2-OE and WT (wild-type) littermates were subjected to chronic anterior coronary artery ligation or sham surgery. Two weeks after MI, ER\u03b2-OE mice showed improved survival (100% and 83% compared with 76% and 58% in WT females and males respectively). ER\u03b2-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 ER\u03b2-mediated myocardial protection. First, male and female ER\u03b2-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 ER\u03b2-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 ER\u03b2-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.<\/jats:p>","DOI":"10.1042\/cs20150609","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T02:33:56Z","timestamp":1448505236000},"page":"365-376","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Cardiomyocyte-specific overexpression of oestrogen receptor \u03b2 improves survival and cardiac function after myocardial infarction in female and male mice"],"prefix":"10.1042","volume":"130","author":[{"given":"Iris","family":"Schuster","sequence":"first","affiliation":[{"name":"EA 2992, Medical University of N\u00eemes-Montpellier, Centre Hospitalo-Universitaire de N\u00eemes, N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokoufeh","family":"Mahmoodzadeh","sequence":"additional","affiliation":[{"name":"Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Dworatzek","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany"},{"name":"Institute of Gender in Medicine and Center for Cardiovascular Research, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Jaisser","sequence":"additional","affiliation":[{"name":"Inserm, U872, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smail","family":"Messaoudi","sequence":"additional","affiliation":[{"name":"Inserm, U872, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Morano","sequence":"additional","affiliation":[{"name":"Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Regitz-Zagrosek","sequence":"additional","affiliation":[{"name":"DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany"},{"name":"Institute of Gender in Medicine and Center for Cardiovascular Research, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,1,26]]},"reference":[{"key":"2021113011063493300_B1","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.jacc.2009.09.065","article-title":"Sex-related differences in myocardial remodeling","volume":"55","author":"Piro","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"2021113011063493300_B2","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s11897-012-0107-7","article-title":"Gender differences in the pathophysiology, clinical presentation, and outcomes of ischemic heart failure","volume":"9","author":"Dunlay","year":"2012","journal-title":"Curr. Heart Fail. Rep."},{"key":"2021113011063493300_B3","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.1161\/CIRCULATIONAHA.106.673442","article-title":"Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program","volume":"115","author":"O'Meara","year":"2007","journal-title":"Circulation"},{"key":"2021113011063493300_B4","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1016\/j.lfs.2004.04.024","article-title":"Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice","volume":"75","author":"Cavasin","year":"2004","journal-title":"Life Sci."},{"key":"2021113011063493300_B5","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0014-5793(97)01179-4","article-title":"Cardiac myocytes and fibroblasts contain functional estrogen receptors","volume":"416","author":"Grohe","year":"1997","journal-title":"FEBS Lett."},{"key":"2021113011063493300_B6","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1096\/fj.05-5148com","article-title":"Estrogen receptor \u03b1 up-regulation and redistribution in human heart failure","volume":"20","author":"Mahmoodzadeh","year":"2006","journal-title":"FASEB J."},{"key":"2021113011063493300_B7","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1161\/01.CIR.0000147610.41984.E8","article-title":"Upregulation of myocardial estrogen receptors in human aortic stenosis","volume":"110","author":"Nordmeyer","year":"2004","journal-title":"Circulation"},{"key":"2021113011063493300_B8","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1093\/cvr\/cvp350","article-title":"17\u03b2-Estradiol inhibits matrix metalloproteinase-2 transcription via MAP kinase in fibroblasts","volume":"85","author":"Mahmoodzadeh","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"2021113011063493300_B9","doi-asserted-by":"publisher","first-page":"12E","DOI":"10.1016\/S0002-9149(02)02405-0","article-title":"Protective effects of estrogen on the cardiovascular system","volume":"89","author":"Mendelsohn","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"2021113011063493300_B10","doi-asserted-by":"publisher","first-page":"50768","DOI":"10.1074\/jbc.M210106200","article-title":"Integration of the non-genomic and genomic actions of estrogen: membrane-initiated signaling by steroid to transcription and cell biology","volume":"277","author":"Pedram","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021113011063493300_B11","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1161\/01.CIR.0000159262.18512.46","article-title":"Increased mortality and aggravation of heart failure in estrogen receptor-\u03b2 knockout mice after myocardial infarction","volume":"111","author":"Pelzer","year":"2005","journal-title":"Circulation"},{"key":"2021113011063493300_B12","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1161\/01.CIR.0000164262.08004.BB","article-title":"Female mice lacking estrogen receptor \u03b2 display prolonged ventricular repolarization and reduced ventricular automaticity after myocardial infarction","volume":"111","author":"Korte","year":"2005","journal-title":"Circulation"},{"key":"2021113011063493300_B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1748-1716.2006.01633.x","article-title":"Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms","volume":"189","author":"Babiker","year":"2007","journal-title":"Acta Physiol."},{"key":"2021113011063493300_B14","doi-asserted-by":"publisher","first-page":"R1597","DOI":"10.1152\/ajpregu.00825.2009","article-title":"Female sex and estrogen receptor-\u03b2 attenuate cardiac remodeling and apoptosis in pressure overload","volume":"298","author":"Fliegner","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021113011063493300_B15","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.pharmthera.2010.04.005","article-title":"Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies","volume":"128","author":"Bernardo","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"2021113011063493300_B16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1161\/CIRCHEARTFAILURE.112.966622","article-title":"Phosphoinositide 3-kinase p110\u03b1 is a master regulator of exercise-induced cardioprotection and PI3K gene therapy rescues cardiac dysfunction","volume":"5","author":"Weeks","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"2021113011063493300_B17","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1073\/pnas.0606663104","article-title":"Protective effects of exercise and phosphoinositide 3-kinase (p110\u03b1) signaling in dilated and hypertrophic cardiomyopathy","volume":"104","author":"McMullen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011063493300_B18","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1093\/cvr\/cvu065","article-title":"Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor \u03b2","volume":"102","author":"Dworatzek","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"2021113011063493300_B19","doi-asserted-by":"publisher","first-page":"R972","DOI":"10.1152\/ajpregu.00045.2009","article-title":"Estrogen receptor \u03b2 mediates increased activation of PI3K\/Akt signaling and improved myocardial function in female hearts following acute ischemia","volume":"296","author":"Wang","year":"2009","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021113011063493300_B20","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1056\/NEJMoa050496","article-title":"The effect of cardiac resynchronization on morbidity and mortality in heart failure","volume":"352","author":"Cleland","year":"2005","journal-title":"New Engl. J. Med."},{"key":"2021113011063493300_B21","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"16","author":"Lang","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"2021113011063493300_B22","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1161\/CIRCRESAHA.110.239574","article-title":"Echocardiographic speckle-tracking based strain imaging for rapid cardiovascular phenotyping in mice","volume":"108","author":"Bauer","year":"2011","journal-title":"Circ. Res."},{"key":"2021113011063493300_B23","doi-asserted-by":"publisher","first-page":"H1765","DOI":"10.1152\/ajpheart.00559.2011","article-title":"New approaches in small animal echocardiography: imaging the sounds of silence","volume":"301","author":"Ram","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011063493300_B24","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1067\/mje.2002.117560","article-title":"Echocardiographic evaluation of ventricular remodeling in a mouse model of myocardial infarction","volume":"15","author":"Kanno","year":"2002","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"2021113011063493300_B25","doi-asserted-by":"publisher","first-page":"e41691","DOI":"10.1371\/journal.pone.0041691","article-title":"New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction","volume":"7","author":"Benavides-Vallve","year":"2012","journal-title":"PLoS One"},{"key":"2021113011063493300_B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.4172\/2157-7013.1000153","article-title":"Cardiomyocyte-specific estrogen receptor \u03b1 increases angiogenesis, lymphangiogenesis and reduces fibrosis in the female mouse heart post-myocardial infarction","volume":"5","author":"Mahmoodzadeh","year":"2014","journal-title":"J. Cell Sci. Ther."},{"key":"2021113011063493300_B27","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1161\/01.CIR.0000127126.73759.23","article-title":"MEK1\u2013ERK2 signaling pathway protects myocardium from ischemic injury in\u00a0vivo","volume":"109","author":"Lips","year":"2004","journal-title":"Circulation"},{"key":"2021113011063493300_B28","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1161\/RES.0b013e318246f187","article-title":"Weighing in on heart failure: the role of SERCA2a SUMOylation","volume":"110","author":"Schwartz","year":"2012","journal-title":"Circ. Res."},{"key":"2021113011063493300_B29","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1161\/CIRCRESAHA.111.259754","article-title":"Modulation of cardiac contractility by the phospholamban\/SERCA2a regulatome","volume":"110","author":"Kranias","year":"2012","journal-title":"Circ. Res."},{"key":"2021113011063493300_B30","doi-asserted-by":"publisher","first-page":"2556","DOI":"10.1074\/jbc.274.4.2556","article-title":"Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene","volume":"274","author":"Periasamy","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2021113011063493300_B31","doi-asserted-by":"publisher","first-page":"H1146","DOI":"10.1152\/ajpheart.00720.2003","article-title":"Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity","volume":"286","author":"Schultz Jel","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011063493300_B32","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1172\/JCI119544","article-title":"Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation","volume":"100","author":"He","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2021113011063493300_B33","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1161\/01.RES.83.12.1205","article-title":"Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts","volume":"83","author":"Baker","year":"1998","journal-title":"Circ. Res."},{"key":"2021113011063493300_B34","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"2021113011063493300_B35","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ijcard.2013.09.002","article-title":"Sex- and estrogen-dependent regulation of a miRNA network in the healthy and hypertrophied heart","volume":"169","author":"Queiros","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"2021113011063493300_B36","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/nature07511","article-title":"MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts","volume":"456","author":"Thum","year":"2008","journal-title":"Nature"},{"key":"2021113011063493300_B37","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1007\/s00395-012-0278-0","article-title":"Role of miR-21\u00a0in the pathogenesis of atrial fibrosis","volume":"107","author":"Adam","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"2021113011063493300_B38","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1161\/CIRCEP.112.973214","article-title":"Role for microRNA-21\u00a0in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure","volume":"5","author":"Cardin","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"2021113011063493300_B39","doi-asserted-by":"publisher","first-page":"4196","DOI":"10.1038\/onc.2011.583","article-title":"Direct regulation of microRNA biogenesis and expression by estrogen receptor \u03b2 in hormone-responsive breast cancer","volume":"31","author":"Paris","year":"2012","journal-title":"Oncogene"},{"key":"2021113011063493300_B40","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/nrd3551","article-title":"Development of subtype-selective oestrogen receptor-based therapeutics","volume":"10","author":"Nilsson","year":"2011","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/5\/365\/447251\/cs1300365.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/5\/365\/447251\/cs1300365.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:03:37Z","timestamp":1638273817000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/130\/5\/365\/77741\/Cardiomyocyte-specific-overexpression-of-oestrogen"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,26]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20150609","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,26]]}}}