Estrogen receptor-β signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice

Dennis Gürgen, Björn Hegner, Angelika Kusch, Rusan Catar, Lyubov Chaykovska, Uwe Hoff, Volkmar Gross, Torsten Slowinski, Andrey C. Da Costa Goncalves, Ulrich Kintscher, Jan Åke Gustafsson, Friedrich C. Luft, Duska Dragun

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-β (ERβ) protects the females from left ventricular hypertrophy, we treated male and female ERβ-deficient (ERβ) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (+16%) heart weight/tibia length ratios compared with WT females (+7%) at 6 weeks. In ERβ mice, this situation was reversed. Female WT mice had the greatest heart weight/tibia length ratio increases of all of the groups (+23%), even greater than ERβ males (+10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ERβ females developed dilative left ventricular hypertrophy. The hypertrophic response in female ERβ mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ERβ females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin Aβ expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ERβ mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ERβ agonist. We conclude that a functional ERβ is essential for inducing adaptive p38 and extracellular signal-regulated kinase signaling, while reducing maladaptive calcineurin signaling in normotensive deoxycorticosterone acetate female mice. Our findings address the possibility of sex-specific cardiovascular therapies.

Original languageEnglish (US)
Pages (from-to)648-654
Number of pages7
JournalHypertension
Volume57
Issue number3 PART 2
DOIs
StatePublished - Mar 2011

Keywords

  • calcineurin
  • ERK1/2
  • estrogen receptor-β, heart
  • fibrosis
  • hypertrophy
  • p38 MAPK

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint

Dive into the research topics of 'Estrogen receptor-β signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice'. Together they form a unique fingerprint.

Cite this