Monash University, Prince Henry's Institute of Medical Research, Cardiovascular Endocrinology Laboratory and Department of Physiology, Clayton, Australia.
Expert Opin Ther Targets. 2013 Mar;17(3):321-31. doi: 10.1517/14728222.2013.748750. Epub 2013 Jan 17.
Over the last two decades, the known functions of the mineralocorticoid receptor (MR) have expanded beyond regulation of sodium and potassium in epithelial cells to encompass physiological and pathophysiological effects in many tissues throughout the body. It is now well accepted that the MR plays a critical role in many aspects of cardiovascular disease.
Recent studies employing tissue-selective MR null mice have added valuable insights into the cellular mechanisms that translate MR activation into cardiac remodeling and dysfunction. Together with earlier pharmacological studies using MR antagonists the apparent protective effects of tissue-selective MR deletion support the observed clinical benefits of MR antagonists in heart failure. Given the potential risk of side effects of current therapies, a key goal is the identification of tissue-selective MR antagonists that will provide cardiovascular protection, but spare renal function. As such, the specific cellular mechanisms regulated by MR located in the cardiovascular system may provide the basis for the development of targeted therapies.
This review will address the function of the MR, and its regulation of the cellular mechanisms that determine cell-specific MR signaling in cardiovascular disease and briefly discuss the potential for novel therapeutic targets that will allow for cardiac selective MR blockade.
在过去的二十年中，人们对盐皮质激素受体（MR）的认识已经超越了对上皮细胞中钠和钾的调节，其在体内许多组织中的生理和病理生理作用也得到了广泛的认识。现在人们普遍认为，MR 在心血管疾病的许多方面都起着关键作用。
最近采用组织特异性 MR 缺失小鼠的研究为将 MR 激活转化为心脏重构和功能障碍的细胞机制提供了有价值的见解。结合早期使用 MR 拮抗剂的药理学研究，组织特异性 MR 缺失的明显保护作用支持了 MR 拮抗剂在心衰中的临床获益。鉴于当前治疗方法存在潜在的副作用风险，一个关键目标是确定组织特异性 MR 拮抗剂，这些拮抗剂将提供心血管保护作用，但不影响肾功能。因此，MR 在心血管系统中的特定细胞机制可能为靶向治疗的发展提供基础。
这篇综述将讨论 MR 的功能及其对决定心血管疾病中细胞特异性 MR 信号的细胞机制的调节，并简要讨论潜在的新治疗靶点，这些靶点将允许心脏选择性 MR 阻断。
