title: Eplerenone reduced lesion size in early but not advanced atherosclerosis in apolipoprotein E-deficient mice.
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·d) 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.
authors.affiliation: Internal Medicine A, Rambam Medical Center, Haifa, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Raz-Pasteur
authors.forename: Aviva
authors.initials: A
authors.lastname: Gamliel-Lazarovich
authors.forename: Raymond
authors.initials: R
authors.lastname: Coleman
authors.forename: Shlomo
authors.initials: S
authors.lastname: Keidar
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D000077545:Eplerenone; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic; D012333:RNA, Messenger / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone; D019405:Cytochrome P-450 CYP11B2