Abstract: The beneficial effects of eplerenone, a specific mineralocorticoid receptor blocker, were previously demonstrated in early atherosclerosis (ATS). The aim of the present study was to evaluate the effect of eplerenone in advanced versus early ATS. Apolipoprotein E knockout mice aged 16 or 32 weeks were randomly divided into eplerenone (100 mg·kg−1·d−1) or vehicle treatment for 14 weeks. Eplerenone reduced atherosclerotic lesion size by 51% only in early ATS. In peritoneal macrophages obtained from these mice, eplerenone reduced messenger RNA expression of pro-inflammatory markers, interleukin 6, tumor necrosis factor α, monocyte chemotactic protein 1, and increased anti-inflammatory marker arginase 1 to a greater extent in early compared with advanced ATS. These changes correspond to macrophage polarization toward alternative inflammatory phenotype. Messenger RNA expression of the mineralocorticoid receptor and aldosterone synthase were also reduced by eplerenone to a greater extent in early ATS, and these might increase the sensitivity of macrophages to mineralocorticoid blockade in early ATS. The results of the present study point to the benefits of early initiation of treatment with eplerenone in reducing experimental ATS.
*Internal Medicine A, Rambam Medical Center, Haifa, Israel
†Lipid Research Laboratory, The Rappaport Family Institute for Research in the Medical Sciences, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology and Rambam Medical Center, Haifa, Israel
‡Department of Anatomy, The Rappaport Family Institute for Research in the Medical Sciences, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel.
Reprints: Shlomo Keidar, MD, The Lipid Research Laboratory, Rambam Medical Center, Haifa 31096, Israel (e-mail: firstname.lastname@example.org).
The authors report no funding or conflicts of interest.
Received May 03, 2012
Accepted August 15, 2012