Estrogen regulation of protein expression and signaling pathways in the heart.

Charles Steenbergen,Elizabeth Murphy

doi:10.1186/2042-6410-5-6

Abstract

Sex differences in cardiovascular disease and cardiac physiology have been reported in humans as well as in animal models. Premenopausal women have reduced cardiovascular disease compared to men, but the incidence of cardiovascular disease in women increases following menopause. Sex differences in cardiomyocytes likely contribute to the differences in male–female physiology and response to disease. Sex differences in the heart have been noted in electrophysiology, contractility, signaling, metabolism, and cardioprotection. These differences appear to be due, at least in part, to differences in gene and protein expression as well as in posttranslational protein modifications. This review will focus primarily on estrogen-mediated male–female differences in protein expression and signaling pathways in the heart and cardiac cells. It should be emphasized that these basic differences are not intrinsically beneficial or detrimental per se; the difference can be good or bad depending on the context and circumstances.

Highlights

Male–female differences in cardiovascular disease (CVD) are well documented
Testosterone can clearly alter gene expression and contribute to sex differences, for simplicity, this review will focus on female sex hormones and primarily on the effects of estrogen
The effects of estrogen differ depending on the relative levels of ERα and ERβ as well as on the complement of co-repressors and co-activators

Summary

Introduction

Male–female differences in cardiovascular disease (CVD) are well documented. There are sex differences in cardiac myocytes, and these differences likely contribute to the differences in male–female response to physiology and disease. MiR-222 has been shown to be downregulated in female hearts and to play a role in regulation of nitric oxide synthase These data support the concept that sex- and estrogen-dependent regulation of gene expression can be mediated, at least in part, by miRNA. Gabel has used 13C NMR and isopotomer analysis and found that compared to those from male mice, hearts from female mice have an increase in the ratio of carbohydrate metabolism to fatty acid oxidation [23] The reason for this difference is unclear; it could be due to species differences and to differences in the relative levels of ERα versus ERβ in the different species. ERβ appears to plan a key role in the sex differences in hypertrophy, the mechanism is likely to be more complicated and is an area that deserves future investigation

Conclusions

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