The endothelial mineralocorticoid receptor: mediator of the switch from vascular health to disease.
The endothelial mineralocorticoid receptor: mediator of the switch from vascular health to disease.
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DOI：
10.1097/mnh.0000000000000306
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发表时间：
2017-03
影响因子：
3.2
通讯作者：
Jaffe IZ
中科院分区：
文献类型：
--
作者：
Davel AP;Anwar IJ;Jaffe IZ
内皮功能障碍是心血管危险因素（CRF）引起的血管疾病的早期特征。在日益增长的肥胖、糖尿病、高血压和心力衰竭人群中，盐皮质激素受体（MR）拮抗剂可改善内皮功能。本文综述了最近的进展，我们了解的具体作用，内皮细胞（EC）MR血管功能的健康和疾病。使用在EC中特异性调节MR表达的转基因小鼠，最近的研究支持新兴的概念，即虽然EC-MR可能在健康中具有保护作用，但在CRF的存在下，EC-MR有助于内皮功能障碍和血管疾病的进展。提出的机制包括EC-MR在降低一氧化氮产生和生物利用度、增加血管氧化应激、调节增强血管硬度的上皮钠通道和增加促进炎症的EC粘附分子中的作用。EC-MR的作用也可能取决于性别、种族或涉及的血管床。最近的进展支持这样的想法，即EC-MR是从血管健康到疾病的转换，以响应CRF的调解人。目前正在对分子机制进行进一步研究，以确定限制EC-MR对心血管风险患者不利影响的治疗干预措施。
Endothelial dysfunction is an early feature of vascular disease induced by cardiovascular risk factors (CRF). In growing populations with obesity, diabetes, hypertension and heart failure, mineralocorticoid receptor (MR) antagonism improves endothelial function. This review summarizes recent advances in our understanding of the specific role of endothelial cell (EC) MR in vascular function in health and disease. Using transgenic mice with MR expression specifically modulated in ECs, recent studies support the emerging concept that while EC-MR may be protective in health, in the presence of CRFs, EC-MR contributes to endothelial dysfunction and progression of vascular disease. Proposed mechanisms include a role for EC-MR in decreased nitric oxide production and bioavailability, increased vascular oxidative stress, regulation of epithelial sodium channels that enhance vascular stiffness, and increased EC adhesion molecules promoting inflammation. The role of EC-MR may also depend on the sex, race, or vascular bed involved. Recent advances support the idea that EC-MR is a mediator of the switch from vascular health to disease in response to CRFs. Further investigation of the molecular mechanism is underway to identify therapeutic interventions that will limit the detrimental effects of EC-MR in patients at cardiovascular risk.