GPER: A Novel Target To Treat Cardiovascular Disease In A Sex‐Specific Manner?

As an agonist of the classical nuclear receptors, ERα and ERβ, estrogen has been understood to inhibit the development of cardiovascular disease in pre-menopausal women. Indeed, reduced levels of estrogen after menopause are believed to contribute to accelerated morbidity and mortality rates in women. However, estrogen replacement therapy has variable effects on cardiovascular risk in post-menopausal women that include increased serious adverse events. Interestingly, pre-clinical studies have shown that selective activation of the novel membrane-associated G protein-coupled estrogen receptor 1, GPER, can promote cardiovascular protection. These benefits are more evident in ovariectomised than intact females or in males. It is therefore possible that selective targeting of the GPER in post-menopausal women could provide cardiovascular protection with fewer adverse effects than are caused by conventional 'receptor non-specific' estrogen replacement therapy. This review describes new data regarding the merits of targeting GPER to treat cardiovascular disease with a focus on sex differences.