Vascular Mineralocorticoid Receptor: Evolutionary Mediator of Wound Healing Turned Harmful by Our Modern Lifestyle.

Abstract

The mineralocorticoid receptor (MR) is indispensable for survival through its critical role in maintaining blood pressure in response to sodium scarcity or bleeding. Activation of MR by aldosterone in the kidney controls water and electrolyte homeostasis. This review summarizes recent advances in our understanding of MR function, specifically in vascular endothelial and smooth muscle cells. The evolving roles for vascular MR are summarized in the areas of (i) vascular tone regulation, (ii) thrombosis, (iii) inflammation, and (iv) vascular remodeling/fibrosis. Synthesis of the data supports the concept that vascular MR does not contribute substantially to basal homeostasis but rather, MR is poised to be activated when the vasculature is damaged to coordinate blood pressure maintenance and wound healing. Specifically, MR activation in the vascular wall promotes vasoconstriction, inflammation, and exuberant vascular remodeling with fibrosis. A teleological model is proposed in which these functions of vascular MR may have provided a critical evolutionary survival advantage in the face of mechanical vascular injury with bleeding. However, modern lifestyle is characterized by physical inactivity and high fat/high sodium diet resulting in diffuse vascular damage. Under these modern conditions, diffuse, persistent and unregulated activation of vascular MR contributes to post-reproductive cardiovascular disease in growing populations with hypertension, obesity, and advanced age.