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

Item Type:Article
Title:Estrogen receptor-β signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice
Creators Name:Guergen, D. and Hegner, B. and Kusch, A. and Catar, R. and Chaykovska, L. and Hoff, U. and Gross, V. and Slowinski, T. and da Costa Goncalves, A.C. and Kintscher, U. and Gustafsson, J.A. and Luft, F.C. and Dragun, D.
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-beta (ERbeta) protects the females from left ventricular hypertrophy, we treated male and female ERbeta-deficient (ERbeta(-/-)) 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 ERbeta(-/-) 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 ERbeta(-/-) males (+10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ERbeta(-/-) females developed dilative left ventricular hypertrophy. The hypertrophic response in female ERbeta(-/-) mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ERbeta(+/+) females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin Abeta expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ERbeta(-/-) mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ERbeta agonist. We conclude that a functional ERbeta 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.
Keywords:Estrogen Receptor-beta, Heart, Hypertrophy, Fibrosis, Calcineurin, p38 MAPK, ERK1/2, Animals, Mice
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:57
Number:3
Page Range:648-654
Date:March 2011
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.110.166157
PubMed:View item in PubMed

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