30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature.
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature.
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DOI：
10.1530/joe-17-0009
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Jaffe IZ
中科院分区：
文献类型：
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作者：
DuPont JJ;Jaffe IZ
自从盐皮质激素受体（MR）在30年前被克隆以来，已经清楚的是，MR在肾外组织中表达，包括心血管系统，其中它在脉管系统的所有细胞上表达。了解MR在血管系统中的作用特别令人感兴趣，因为临床试验表明MR拮抗作用改善心血管结局与血压变化不成比例。近30年来的研究表明，MR是血管平滑肌细胞和内皮细胞中一种功能性的转录因子。本文综述了血管MR在调节血压和血管功能以及促进血管疾病方面的作用。具体而言，血管MR直接有助于血压控制和血管功能障碍以及响应于高血压、肥胖和血管损伤的重塑。本文总结了血管MR在以下疾病中的作用：肺动脉高压;脑血管重塑和卒中;血管炎症、动脉粥样硬化和心肌梗死;急性肾损伤;以及眼部血管病理学。还描述了关于年龄和性别对血管MR功能的影响的考虑。进一步研究MR促进这些过程的精确分子机制将有助于识别新的治疗靶点，以降低CVD相关的发病率和死亡率。
Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed on all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in our understanding of the role of vascular MR in regulating blood pressure and vascular function and contributing to vascular disease. Specifically, vascular MR contributes directly to blood pressure control and to vascular dysfunction and remodeling in response to hypertension, obesity and vascular injury. The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye. Considerations regarding the impact of age and sex on the function of vascular MR are also described. Further investigation of the precise molecular mechanisms by which MR contributes to these processes will aid in the identification of novel therapeutic targets to reduce CVD-related morbidity and mortality.