Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Research Service, Harry S Truman Memorial Veterans Hospital, Research Service, 800 Hospital Dr, Columbia, MO 65212, USA.
Cardiovasc Res. 2017 Jul 1;113(9):1055-1063. doi: 10.1093/cvr/cvx097.
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.
血管功能障碍和内皮介导的舒张功能受损是高血压、冠心病和中风发病机制中的强大潜在异常。肥胖、2 型糖尿病和其他代谢异常与血管和脂肪组织中醛固酮受体 (MRs) 的激活有关。虽然 MR 信号参与了脂肪细胞的正常生理分化和成熟,但 MRs 的过度激活也会导致氧化应激增加、促炎脂肪因子释放和脂肪细胞自噬失调。反过来,这会增加皮下、内脏和血管周围脂肪组织的适应性扩张,导致全身和心血管 (CV) 胰岛素抵抗以及 CV 僵硬和血管及心脏舒张功能受损。本文总结了 MR 激活在脂肪组织中的正常作用,并探讨了过度的 MR 激活介导脂肪组织炎症和血管功能障碍的机制。还讨论了针对预防 MR 激活和心血管疾病的潜在预防和治疗策略。