Klinik fuer Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Eur J Clin Invest. 2012 Oct;42(10):1112-20. doi: 10.1111/j.1365-2362.2012.02676.x. Epub 2012 Apr 26.
The classical view of aldosterone actions via the mineralocorticoid receptor (MR) limited to control of fluid balance and blood pressure homoeostasis has been progressively overcome by clinical and experimental evidence emphasizing the pleiotropic role of MR activation in the pathogenesis of cardiovascular disease. Clinical studies have shown the benefit of MR blockade in patients with left ventricular dysfunction and heart failure after myocardial infarction (MI), hypertension or diabetic nephropathy. Deleterious effects of MR activation include cardiac structural and electrical remodelling, cardiovascular fibrosis, inflammation and oxidative stress. Complexity of pathophysiological role of MR derives from the presence of circulating glucocorticoids at higher concentrations than aldosterone and the equal affinity of the MR for aldosterone, cortisol and corticosterone. Recent experimental studies using different animal models and genetic tools have deeply explored the cell-specific functional role of MR in cardiovascular pathology. This review addresses emerging preclinical studies as well as ongoing clinical trials regarding MR activation in MI and failure.
经典观点认为醛固酮通过盐皮质激素受体 (MR) 发挥作用,仅限于控制液体平衡和血压稳态,但临床和实验证据逐渐克服了这一观点,强调了 MR 激活在心血管疾病发病机制中的多效性作用。临床研究表明,MR 阻断在左心室功能障碍和心肌梗死后心力衰竭 (MI)、高血压或糖尿病肾病患者中有益。MR 激活的有害作用包括心脏结构和电重构、心血管纤维化、炎症和氧化应激。MR 病理生理学作用的复杂性源于循环中糖皮质激素的浓度高于醛固酮,以及 MR 对醛固酮、皮质醇和皮质酮具有同等亲和力。最近使用不同动物模型和遗传工具的实验研究深入探讨了 MR 在心血管病理学中的细胞特异性功能作用。这篇综述讨论了关于 MI 和心力衰竭中 MR 激活的新兴临床前研究和正在进行的临床试验。