title: Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
abstract: We investigated sex differences and the role of estrogen receptor-beta (ERbeta) on myocardial hypertrophy in a mouse model of pressure overload. We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta(-/-)) mice. All mice were characterized by echocardiography and hemodynamic measurements and were killed 9 wk after surgery. Left ventricular (LV) samples were analyzed by microarray profiling, real-time RT-PCR, and histology. After 9 wk, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that WT male hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than WT female hearts. ERbeta(-/-) mice exhibited a different transcriptional response. ERbeta(-/-)/TAC mice of both sexes exhibited induction of proapoptotic genes with a stronger expression in ERbeta(-/-) males. Cardiac fibrosis was more pronounced in male WT/TAC than in female mice. This difference was abolished in ERbeta(-/-) mice. The number of apoptotic nuclei was increased in both sexes of ERbeta(-/-)/TAC mice, most prominent in males. Female sex offers protection against ventricular chamber dilation in the TAC model. Both female sex and ERbeta attenuate the development of fibrosis and apoptosis, thus slowing the progression to heart failure.
authors.affiliation: Institute of Gender in Medicine, Charité-Medical University Berlin, Germany. daniela.fliegner@charite.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Fliegner
authors.forename: Carola
authors.initials: C
authors.lastname: Schubert
authors.forename: Adam
authors.initials: A
authors.lastname: Penkalla
authors.forename: Henning
authors.initials: H
authors.lastname: Witt
authors.forename: Georgios
authors.initials: G
authors.lastname: Kararigas
authors.forename: George
authors.initials: G
authors.lastname: Kararigas
authors.forename: Elke
authors.initials: E
authors.lastname: Dworatzek
authors.forename: Eike
authors.initials: E
authors.lastname: Staub
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz Noppinger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D003251:Constriction, Pathologic / Q000473:pathology; D004452:Echocardiography; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011312:Pressure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
chemical_list: D047629:Estrogen Receptor beta