Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis.
Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis.
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DOI：
10.1038/nrneph.2013.110
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发表时间：
2013-08
影响因子：
41.5
通讯作者：
Brown, Nancy J.
中科院分区：
文献类型：
--
作者：
Brown, Nancy J.
类固醇激素醛固酮调节钠和钾的体内平衡。醛固酮和盐皮质激素受体的活化还引起心脏的炎症和纤维化、血管的纤维化和重塑以及肾中的肾小管间质纤维化和肾小球损伤。醛固酮和盐皮质激素受体激活通过增加烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶和线粒体产生活性氧来启动炎症反应。高盐摄入增强了这些作用，部分是通过激活Rho家族成员Rac 1，一种激活盐皮质激素受体的还原型NADPH氧化酶的调节亚基。在小鼠中进行的盐皮质激素受体已从特定细胞类型中删除的研究表明，巨噬细胞在促进炎症和纤维化中起关键作用。醛固酮可通过血管紧张素II受体和G蛋白偶联受体30发挥盐皮质激素受体非依赖性作用。盐皮质激素受体拮抗剂可降低心脏病患者的死亡率，对肾损伤患者也有一定的疗效，但可升高血清钾浓度。在啮齿类动物中进行的醛固酮合酶基因缺陷或用药理学醛固酮合酶抑制剂治疗的研究，提供了对醛固酮与盐皮质激素受体激活在炎症、纤维化和损伤中的相对贡献的深入了解。醛固酮合成酶抑制剂正在开发中的人类。
The steroid hormone aldosterone regulates sodium and potassium homeostasis. Aldosterone and activation of the mineralocorticoid receptor also causes inflammation and fibrosis of the heart, fibrosis and remodelling of blood vessels and tubulointerstitial fibrosis and glomerular injury in the kidney. Aldosterone and mineralocorticoid-receptor activation initiate an inflammatory response by increasing the generation of reactive oxygen species by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. High salt intake potentiates these effects, in part by activating the Rho family member Rac1, a regulatory subunit of reduced NADPH oxidase that activates the mineralocorticoid receptor. Studies in mice in which the mineralocorticoid receptor has been deleted from specific cell types suggest a key role for macrophages in promoting inflammation and fibrosis. Aldosterone can exert mineralocorticoid-receptor-independent effects via the angiotensin II receptor and via G-protein-coupled receptor 30. Mineralocorticoid-receptor antagonists are associated with decreased mortality in patients with heart disease and show promise in patients with kidney injury, but can elevate serum potassium concentration. Studies in rodents genetically deficient in aldosterone synthase or treated with a pharmacological aldosterone-synthase inhibitor are providing insight into the relative contribution of aldosterone compared with the contribution of mineralocorticoid-receptor activation in inflammation, fibrosis, and injury. Aldosterone-synthase inhibitors are under development in humans.
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