Mineralocorticoid receptors in vascular disease: connecting molecular pathways to clinical implications.

Mineralocorticoid receptors in vascular disease: connecting molecular pathways to clinical implications.
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DOI:
10.1007/s11883-013-0340-x
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发表时间:
2013-07
影响因子:
5.8
通讯作者:
Jaffe IZ
Jaffe IZ
中科院分区:
医学2区
文献类型:
--
作者:
McGraw AP;McCurley A;Preston IR;Jaffe IZ

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盐皮质激素受体(MR)是一种类固醇激素激活的转录因子,在心血管疾病中起重要作用。MR拮抗剂(MRA)长期以来一直被认为是心力衰竭和高血压的有效治疗方法;然而,最近的研究表明,其他患者人群也可能受益于MRA治疗。实验证据表明,除了其在肾脏中调节钠处理的经典作用之外,功能性MR在血管中表达,并有助于高血压、血管炎症和重塑以及动脉粥样硬化形成。MR激活驱动平滑肌细胞、内皮细胞和炎性细胞的病理表型,而MRA抑制这些作用。总的来说,这些研究证明了肾外MR在心血管疾病中的新作用。本文综述了这些新的证据,以及它们如何有助于动脉粥样硬化,肺动脉和全身性高血压,静脉移植失败的机制,并描述了新的患者人群,可能受益于MRA治疗。
The mineralocorticoid receptor (MR), a steroid hormone-activated transcription factor, plays a substantial role in cardiovascular diseases. MR antagonists (MRAs) have long been appreciated as effective treatments for heart failure and hypertension; however, recent research suggests that additional patient populations may also benefit from MRA therapy. Experimental evidence demonstrates that in addition to its classical role in the regulating sodium handling in the kidney, functional MR is expressed in the blood vessels and contributes to hypertension, vascular inflammation and remodeling, and atherogenesis. MR activation drives pathological phenotypes in smooth muscle cells, endothelial cells and inflammatory cells, while MRAs inhibit these effects. Collectively, these studies demonstrate a new role for extra-renal MR in cardiovascular disease. This review summarizes these new lines of evidence and how they contribute to mechanisms of atherosclerosis, pulmonary and systemic hypertension, and vein graft failure, and describes new patient populations that may benefit from MRA therapy.
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