title: Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.
abstract: The aim of this study was to investigate the effects of 17β-estradiol (E2), the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM) raloxifene on remodeling processes during the development of myocardial hypertrophy (MH) in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC). Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF) was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFβ and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period.
authors.affiliation: Charité - Universitätsmedizin Berlin, Institute of Gender in Medicine, Berlin, Germany. christina.westphal@mdc-berlin.de
authors.forename: Christina
authors.initials: C
authors.lastname: Westphal
authors.forename: Carola
authors.initials: C
authors.lastname: Schubert
authors.forename: Katja
authors.initials: K
authors.lastname: Prelle
authors.forename: Adam
authors.initials: A
authors.lastname: Penkalla
authors.forename: Daniela
authors.initials: D
authors.lastname: Fliegner
authors.forename: George
authors.initials: G
authors.lastname: Petrov
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D003251:Constriction, Pathologic; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011312:Pressure; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D013599:Systole / Q000187:drug effects; D014463:Ultrasonography; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha; D004967:Estrogens; D016326:Extracellular Matrix Proteins; D020849:Raloxifene Hydrochloride