Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:454-460
Published online before print January 30, 2003, doi: 10.1161/01.ATV.0000059419.11002.6E
Published online before print January 30, 2003, doi: 10.1161/01.ATV.0000059419.11002.6E
© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Influence of Interferon-
on the Extent and Phenotype of Diet-Induced Atherosclerosis in the LDLR-Deficient Mouse
From the Immunology Research Division (C.B., C.E.C., A.H.L.) and the Vascular Research Division (G.S., A.H.L.), Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; and the J. Alick Little Lipid Research Laboratory, St Michael’s Hospital, and the Departments of Laboratory Medicine and Pathobiology, Biochemistry, and Medicine (G.F.M., P.W.C.), University of Toronto, Toronto, Canada.
Correspondence to Andrew H. Lichtman, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail alichtman{at}rics.bwh.harvard.edu
Objective— The aim of this study was to investigate the influence of interferon-
(IFN-) on atherosclerosis in low density lipoprotein receptor (LDLR)–null mice.
Methods and Results— We cross-bred IFN-–deficient mice with LDLR-null mice and analyzed lipoprotein profiles and atherosclerosis in the compound mutant progeny after 8 and 20 weeks on a cholesterol-enriched diet. IFN- deficiency did not affect serum cholesterol levels or lipoprotein profiles, but it did affect the extent and phenotype of atherosclerosis. Atherosclerotic lesions in IFN-–deficient mice were reduced by 75% in the aortic arch and by 46% in the descending aorta compared with control mice after 8 weeks on the diet. After 20 weeks, arch lesions were reduced by 43%, and descending aorta lesions were reduced by 65% in IFN-–deficient mice compared with controls. At 8 weeks, percent lesional macrophage and smooth muscle content was significantly less in the IFN-–deficient mice, but not at 20 weeks. Although there were fewer class II major histocompatibility complex–positive cells in the lesions of IFN-–deficient animals compared with controls, class II major histocompatibility complex expression on endothelial cells overlying lesions persisted in the absence of IFN-.
Conclusions— These data provide direct evidence that IFN- influences atherosclerosis development and phenotype in the LDLR-deficient mouse, independent of changes in blood lipoprotein profiles.
Key Words: atherosclerosis • cytokines • endothelium • mouse • T cells
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