The role ofmineralocorticoid receptor signaling in the cross-talk between adipose tissue and the vascular wall

Abstract

Vascular dysfunction and impaired endothelial mediated relaxation are powerful underlying abnormalities in the pathogenesis of hypertension, coronary heart disease, and stroke. Obesity, type 2 diabetes mellitus, and other metabolic abnormalities are associated with activation of mineralocorticoid receptor (MRs) in the vasculature and adipose tissue. While MR signaling is involved in the normal physiological differentiation and maturation of adipocyte, enhanced activation of MRs also contributes to increase oxidative stress, release of pro-inflammatory adipokines, and dysregulation of adipocyte autophagy. This, in turn, increases the maladaptive expansion of subcutaneous, visceral and perivascular adipose tissue, resulting in systemic and cardiovascular (CV) insulin resistance and increased CV stiffness and impaired vascular and cardiac relaxation. This review summarizes the normal role of MR activation in adipose tissues and explores the mechanisms by which excessive MR activation mediates adipose tissue inflammation and vascular dysfunction. Potential preventative and therapeutic strategies directed in the prevention of MR activation and CV disease are also discussed.