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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1250.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Humoral Immune Response Against Defined Oxidized Low-Density Lipoprotein Antigens Reflects Structure and Disease Activity of Carotid Plaques

Isabel Gonçalves; Marie-Louise M. Gronholdt; Ingrid Söderberg; Mikko P.S. Ares; Borge G. Nordestgaard; Jacob F. Bentzon; Gunilla Nordin Fredrikson; Jan Nilsson

From the Departments of Medicine (I.G., I. S., M.P.S.A., G.N.F., J.N.) and Cardiology (I.G.), Lund University, Wallenberg Laboratory, University Hospital MAS, Malmö, Sweden; the Department of Vascular Surgery (M.L.G.), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; the Department of Clinical Biochemistry (B.N.), Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark; and the Department of Coronary Pathology Research (J.F.B.), Skejby University Hospital, Århus, Denmark.

Correspondence to Isabel Gonçalves, University of Lund, Wallenberg Laboratory, University Hospital MAS, SE-20502 Malmö, Sweden. E-mail isabel.goncalves{at}medforsk.mas.lu.se

Background— Immune responses against oxidized low-density lipoprotein (LDL) play an important role in atherosclerosis. The aim of this study was to investigate if humoral immune response against specific oxidized LDL antigens, such as aldehyde-modified peptide sequences of apolipoprotein B-100, reflects disease activity and structure of atherosclerotic plaques.

Methods and Results— Plaques were obtained from 114 symptomatic subjects referred to carotid endarterectomy and characterized immunohistochemically and histologically. Plasma levels of IgG and IgM against aldehyde-modified apolipoprotein B-100 amino acid sequences 661 to 680, 3136 to 3155 (peptide 210), and 3661 to 3680 (peptide 240) were determined by enzyme-linked immunosorbent assay. High levels of IgG against peptide 210 were associated with increased plaque content of lipids (r=0.24, P<0.05) and hemorrhage (r=0.27, P=0.005), with decreased content of fibrous tissue (r=–0.25, P=0.01), but also with lower total plaque volume (r=–0.21, P<0.05). In contrast, high levels of IgM against peptide 240 were associated with plaques with more fibrous tissue (r=0.35, P<0.001), less lipids (r=–0.34, P<0.001), and less macrophages (r=–0.24, P<0.05). IgM against peptide 210 were found to be associated with plaque fibrous tissue (r=0.20, P<0.05), less lipids (r=–0.21, P<0.05), and less macrophages (r=–0.27, P=0.01).

Conclusion— These findings support the notion that immune responses against oxidized LDL epitopes are involved in atherosclerosis and that the level of circulating antibodies against these structures may reflect disease activity in the arterial wall.

Immune responses against oxidized low-density lipoprotein (LDL) are important in atherosclerosis. This study demonstrates that IgG and IgM against defined epitopes in oxidized LDL reflects the structure and disease activity of atherosclerotic plaques.

Key Words: antibodies • atherosclerosis • carotid plaque • carotid stenosis • modified low-density lipoprotein

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