Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:108-114
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
LDL Immunization Induces T-Cell–Dependent Antibody Formation and Protection Against Atherosclerosis
From the Centre for Molecular Medicine and King Gustaf V Research Institute (A.H.), Karolinska Institutet, Stockholm, Sweden.
Correspondence to Dr Göran K. Hansson, Centre for Molecular Medicine L8:03, Karolinska Hospital, S-17176 Stockholm, Sweden. E-mail Goran.Hansson{at}cmm.ki.se
Abstract—Atherosclerosis is an inflammatory disease, and the involvement of immune mechanisms in disease progression is increasingly recognized. Immunization with oxidized low density lipoprotein (LDL) decreases atherosclerosis in several animal models. To explore humoral and cellular immune reactions involved in this protection, we immunized apolipoprotein E knockout mice with either homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. Immunization with both these antigen preparations reduced lesion development. The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA–very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell–dependent antibody response was associated with protection against atherosclerosis. The protection was associated with specific T-cell–dependent elevation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion formation and lower serum cholesterol levels.
Key Words: atherosclerosis • immunization • low density lipoproteins • antibodies • T cells
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|
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