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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/R1644    most recent 00511.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dimayuga, P. C. Articles by Chyu, K.-Y. Search for Related Content PubMed PubMed Citation Articles by Dimayuga, P. C. Articles by Chyu, K.-Y.

INFLAMMATION AND CYTOKINES

Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(–/–) mice

Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, California

Submitted 12 July 2005 ; accepted in final form 2 July 2006

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(–/–) mice. Mice fed a Western diet were euthanized at 15–17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.

antibodies; atherosclerosis; oxidized low-density lipoprotein