当前位置： SCI文献检索 > ENDOCRINOLOGY期刊下所有文献 > Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.

Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.

Abstract：

:Hypertrophic cardiomyopathy (HCM) is more severe in male than female mice eating a soy-based diet. We sought to determine whether the detrimental effects are mediated by the phytoestrogens present in soy, the mechanism by which phytoestrogens act, and to test whether estrogen modulates the sexually dimorphic phenotype. A soy-free diet (casein based) supplemented with the predominant phytoestrogens in soy, genistein and daidzein, recapitulated the fibrotic, proapoptotic and negative hemodynamic effects of soy in male hearts. As with the soy diet, the hearts of female HCM mice were not negatively affected by the phytoestrogen-containing diet. To determine the role of estrogen in the sex differences mediated by diet in HCM, gonadectomies were performed and estrogen was administered to male and female HCM mice on a casein- or phytoestrogen-supplemented diet. Somewhat surprisingly, estrogen was not protective in male or female mice with HCM and, in fact, was lethal in phytoestrogen-fed male mice with HCM. Because genistein is a potent tyrosine kinase inhibitor and tyrosine kinase inhibition has been associated with cardiotoxicity, we tested its effects in isolated adult cardiac myocytes. Genistein inhibited different tyrosine kinases depending on sex and, in combination with estrogen, resulted in apoptosis only in adult male cardiac myocytes. Finally, we show that phytoestrogens led to distinct programs of gene expression in hearts from males vs. females with HCM, suggesting mechanisms by which males are more sensitive to the detrimental effects of phytoestrogens and females are protected. These results implicate the phytoestrogen genistein in mediating cardiac pathology in males with HCM and, importantly, establish that estrogen is not protective in the setting of HCM.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Haines CD,Harvey PA,Luczak ED,Barthel KK,Konhilas JP,Watson PA,Stauffer BL,Leinwand LA

doi

10.1210/en.2012-1391

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

4470-9

issue

eissn

0013-7227

issn

1945-7170

pii

en.2012-1391

journal_volume

153

pub_type

杂志文章

在线工具

Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.