Department of Medicine, Division of Endocrinology, University of Missouri, Columbia, MO, USA.
Research Service Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
Curr Hypertens Rep. 2018 Aug 14;20(10):88. doi: 10.1007/s11906-018-0887-6.
In the present review, we will discuss the evidence and the mechanisms underlying the complex interplay between obesity, mineralocorticoid receptor activation, and cardiovascular dysfunction with special emphasis on the pathogenesis of cardiovascular disease (CVD) in obese and insulin-resistant females.
Since the initial isolation of aldosterone in 1953 and the cloning of the mineralocorticoid receptor (MR) decades later, our understanding has expanded tremendously regarding their involvement in the pathogenesis of CVD. Recent results from both pre-clinical and clinical studies support a close correlation between increase adiposity and enhanced aldosterone production (MR activation). Importantly, insulin resistance and obese females are more prone to the deleterious cardiovascular effects of MR activation, and enhanced MR activation in females has emerged as an important causative event in the genesis of a more severe CVD in diabetic women. Different clinical trials have been completed examining the effect of MR blockade in subjects with CVD. Despite its important beneficial mortality impact, side effects are frequent and a newer MR antagonist, finerenone, with less risk of hyperkalemia is currently being tested in large clinical trials.
在本综述中，我们将讨论肥胖、醛固酮受体激活与心血管功能障碍之间复杂相互作用的证据和机制，特别强调肥胖和胰岛素抵抗女性心血管疾病（CVD）发病机制。
自 1953 年首次分离出醛固酮和几十年后克隆出矿物质皮质激素受体（MR）以来，我们对它们在 CVD 发病机制中的作用的理解有了巨大的扩展。来自临床前和临床研究的最新结果支持脂肪量增加和醛固酮生成（MR 激活）之间的密切相关性。重要的是，胰岛素抵抗和肥胖女性更容易受到 MR 激活的不良心血管影响，并且女性中增强的 MR 激活已成为糖尿病女性更严重 CVD 发生的重要致病事件。已经完成了多项临床试验，以研究 MR 阻断在 CVD 患者中的作用。尽管它对死亡率有重要的有益影响，但副作用很常见，一种新型 MR 拮抗剂非奈利酮，因其低钾血症风险较低，目前正在大型临床试验中进行测试。
