期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 726, 期 -, 页码 96-108出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2014.01.043
关键词
Macrophage; Heart failure; Eplerenone; Aldosterone; IL-4
Alternative activation of macrophages plays protective role in cardiac remodelling in heart failure and the activity of mineralocorticoid receptor may determine the phenotype of these cells. We examined the influence of eplerenone, aldosterone, and IL-4 on descriptors of alternative activation in blood monocytes collected from 19 patients with heart-failure and 20 healthy volunteers. Heart failure macrophages in comparison with healthy macrophages had increased mineralocorticoid activity, NO and reactive oxygen species production, expression of iNOS mRNA and protein, but decreased expression of arginase I and mannose receptor proteins, and activity of MnSOD and CuZnSOD. Aldosterone increased mineralocorticoid activity, NO and reactive oxygen species production, iNOS mRNA and protein expression, MnSOD and CuZnSOD activity. Eplerenone attenuated the effects of aldosterone on all but MnSOD and CuZnSOD variables. Eplerenone alone increased the production of NO, MnSOD and CuZnSOD activity, arginase I gene and protein expression, and mannose receptor gene and protein expression, but decreased mincralocorticoicl activity only in heart failure macrophages. The latter suggests altered function of mineralocorticoid receptor in heart failure. Increased mincralocorticoicl activity accounts for increased NO production, iNOS gene and protein expression but does not explain the increased basal reactive oxygen species production and decreased markers of alternative activation in heart failure macrophages. In the lack of change in basal mineralocorticoid activity, eplerenone increases markers of alternative activation in a mineralocorticoid receptor independent manner. Because of changes in iNOS and NO variable, eplerenone induced qualitatively different activation of macrophages horn that obtained with IL-4. (C) 2014 Published by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据