Female sex and estrogen receptor-β attenuate cardiac remodeling and apoptosis in pressure overload

Daniela Fliegner, Carola Schubert, Adam Penkalla, Henning Witt, George Kararigas, Elke Dworatzek, Eike Staub, Peter Martus, Patricia Ruiz Noppinger, Ulrich Kintscher, Jan Åke Gustafsson, Vera Regitz-Zagrosek

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

We investigated sex differences and the role of estrogen receptor-β (ERβ) 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 ERβ knockout (ER-/-) 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 RTPCR, 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. ERβ 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. ER-/- mice exhibited a different transcriptional response. ER-/-/TAC mice of both sexes exhibited induction of proapoptotic genes with a stronger expression in ER-/- males. Cardiac fibrosis was more pronounced in male WT/TAC than in female mice. This difference was abolished in ER-/- mice. The number of apoptotic nuclei was increased in both sexes of ER-/-/ TAC mice, most prominent in males. Female sex offers protection against ventricular chamber dilation in the TAC model. Both female sex and ERβ attenuate the development of fibrosis and apoptosis, thus slowing the progression to heart failure.

Original languageEnglish (US)
Pages (from-to)R1597-R1606
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Heart failure

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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