Female Sex and Er-Alpha Modulate Cardiac Ischaemic Remodeling : Cardiomyocyte-specific overexpression of estrogen receptor alpha provides cardioprotection in female mice

In this study, we present novel insights into mechanisms that account for the ER-dependent myocardial protection against myocardial injury, with more beneficial effects in female hearts. Using a transgenic mouse model with a cardiomyocyte-specific ER-overexpression (ER-OE), we first demonstrated that this was associated with an increase of LVM at the basal level in both female and male mice. After MI, the cardiomyocyte-specific ER-OE inhibited changes in LV-volumes and wall thickness only in female mice. These beneficial effects in female ER-OE hearts were associated with increased angiogenesis and lymphangiogenesis, attenuated ventricular fibrosis and enhanced JNK phosphorylation. This study indicates that in the female sex, ER in cardiomyocytes may have a therapeutic potential in the treatment of ischemic heart disease, leading to more efficient cardiac repair after ischemic injury.