Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
Mol Cell Endocrinol. 2012 Mar 24;350(2):256-65. doi: 10.1016/j.mce.2011.06.014. Epub 2011 Jun 24.
The mineralocorticoid receptor (MR), a member of the steroid receptor family, regulates blood pressure by mediating the effects of the hormone aldosterone (Aldo) on renal sodium handling. Over the past decade, it has become clear that MR is expressed in the cardiovascular system and interest has grown in understanding the direct role of the MR in regulating vascular function and contributing to cardiovascular disease. This interest stems from multiple clinical studies in which drugs that decrease MR activation also reduce the incidence of heart attacks, strokes, and mortality out of proportion to modest changes in systemic blood pressure. The presence of functional mineralocorticoid receptors in vascular smooth muscle and endothelial cells is now well established and, while still controversial, data supports the vasculature as an Aldo-responsive tissue. This review summarizes recent advances in our understanding of the role of vascular MR in regulating normal vascular function and in promoting vascular disease. In vitro data, in vivo animal studies, and human data are reviewed suggesting a role for MR-activation in promoting vascular oxidative stress, inhibiting vascular relaxation, and contributing to vessel inflammation, fibrosis, and remodeling. These detrimental vascular effects of MR activation appear to be independent of changes in blood pressure and are synergistic with the presence of endothelial dysfunction or damage. Thus, in humans with underlying cardiovascular disease or cardiovascular risk factors, vascular MR activation may promote vascular aging and atherosclerosis thereby contributing to the pathophysiology of heart attack, stroke, and possibly even hypertension. Further exploration of the molecular mechanisms for the detrimental vascular effects of MR activation has the potential to identify novel therapeutic targets to prevent or treat common cardiovascular disorders.
醛固酮受体（MR）是甾体激素受体家族的一员，通过调节激素醛固酮（Aldo）对肾脏钠处理的作用来调节血压。在过去的十年中，已经清楚地表明，MR 在心血管系统中表达，并且人们越来越感兴趣地了解 MR 对调节血管功能的直接作用以及对心血管疾病的贡献。这种兴趣源于多项临床研究，这些研究表明，降低 MR 激活的药物也会降低心脏病发作、中风和死亡率，而对全身血压的适度变化的影响不成比例。血管平滑肌和内皮细胞中功能性盐皮质激素受体的存在现在已经得到很好的确立，尽管仍然存在争议，但数据支持血管作为对 Aldo 有反应的组织。这篇综述总结了我们对血管 MR 在调节正常血管功能和促进血管疾病中的作用的最新认识。综述了体外数据、体内动物研究和人类数据，表明 MR 激活在促进血管氧化应激、抑制血管舒张以及促进血管炎症、纤维化和重塑方面发挥作用。MR 激活的这些有害血管作用似乎独立于血压变化，并且与内皮功能障碍或损伤的存在具有协同作用。因此，在患有潜在心血管疾病或心血管危险因素的人群中，血管 MR 激活可能会促进血管衰老和动脉粥样硬化，从而导致心脏病发作、中风甚至高血压的病理生理学。进一步探索 MR 激活的有害血管作用的分子机制有可能确定预防或治疗常见心血管疾病的新的治疗靶点。
