Mineralocorticoid and estrogen receptors as sex-dependent modulators of vascular health in aging and obesity

Abstract

Cardiovascular disease (CVD) is the leading cause of death in both men and women, but there are sex differences in the timing and mechanisms of disease development. Sex differences particularly influence the development of CVD in the presence of aging and obesity, 2 major risk factors of CVD. The mineralocorticoid and estrogen receptors have been identified as important regulators of vascular function in healthy and disease states. Recent evidence has highlighted interactions between these receptors in the vasculature, and innovations in global and cell-specific knockout mouse models have substantially advanced our understanding of sex-dependent roles of these receptors in vascular health and disease. This review summarizes recent advances in the sex-dependent roles of the mineralocorticoid and estrogen receptors in arterial stiffness and vasomotor dysfunction, 2 early markers of CVD development. These vascular outcomes are examined in the context of aging and obesity, 2 of the most prevalent CVD risk factors. SIGNIFICANCE STATEMENT: Cardiovascular disease (CVD) is the leading cause of death globally for women and men, but there are sex differences in the timing of CVD development across the lifespan and in mechanisms driving disease. This review summarizes sex-specific roles of mineralocorticoid and estrogen receptors in arterial stiffness and vasomotor dysfunction during aging and obesity. Understanding sex-specific mechanisms of CVD is critical to developing precision medicine strategies to prevent and treat CVD in women and men.

Keywords: Estrogen; Estrogen receptor; Mineralocorticoid; Obesity; Vascular.