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Eplerenone Reduced Lesion Size in Early but Not Advanced Atherosclerosis in Apolipoprotein EDeficient Mice

Raz-Pasteur, Ayelet MD*,†; Gamliel-Lazarovich, Aviva MSc; Coleman, Raymond PhD; Keidar, Shlomo MD*,†

Journal of Cardiovascular Pharmacology: December 2012 - Volume 60 - Issue 6 - p 508–512
doi: 10.1097/FJC.0b013e31826f5535
Original Article

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: skeidar@rambam.health.gov.il).

The authors report no funding or conflicts of interest.

Received May 03, 2012

Accepted August 15, 2012

© 2012 Lippincott Williams & Wilkins, Inc.