Estrogen receptor-beta signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice.
Hypertension
; 57(3): 648-54, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-21300662
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-ß (ERß) protects the females from left ventricular hypertrophy, we treated male and female ERß-deficient (ERß(-/-)) 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 ERß(-/-) 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 ERß(-/-) males (+10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ERß(-/-) females developed dilative left ventricular hypertrophy. The hypertrophic response in female ERß(-/-) mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ERß(+/+) females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin Aß expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ERß(-/-) mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ERß agonist. We conclude that a functional ERß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caracteres Sexuais
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Hipertrofia Ventricular Esquerda
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Receptor beta de Estrogênio
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Desoxicorticosterona
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Mineralocorticoides
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article