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

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Item Type:	Article
Title:	Estrogen receptor-β signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice
Creators Name:	Gürgen, D., Hegner, B., Kusch, A., Catar, R., Chaykovska, L., Hoff, U., Gross, V., Slowinski, T., da Costa Goncalves, A.C., Kintscher, U., Gustafsson, J.A., 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
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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