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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:879.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences

Gunilla Nordin Fredrikson; Ingrid Söderberg; Marie Lindholm; Paul Dimayuga; Kuang-Yuh Chyu; Prediman K. Shah; Jan Nilsson

From the Department of Medicine (G.N.F., I.S., M.L., P.D., J.N.), Malmö University Hospital, Lund University, Sweden; Department of Biomedical Laboratory Science (G.N.F.), Malmö University, Sweden; and Atherosclerosis Research Center (K.-Y.C., P.K.S.), Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Gunilla Nordin Fredrikson, Wallenberg Laboratory, 1st Floor, Malmö University Hospital, 205 02 Malmö, Sweden. E-mail Gunilla.Nordin_Fredrikson{at}medforsk.mas.lu.se

Objective— LDL oxidation is believed to play an important role in the development of atherosclerosis, and oxidized LDL particles have been shown to become targets for the immune system. Immunization of animals with oxidized LDL results in reduction of atherosclerosis, suggesting an atheroprotective effect of this immune response.

Methods and Results— Using a polypeptide library covering the complete sequence of apoB-100, a large number of native and malondialdehyde-modified peptide sequences in apoB-100 that are recognized by antibodies in human plasma were identified. We report here that immunization with apoB-100 peptide sequences, against which high levels of IgG and IgM antibodies are present in healthy human controls, reduce atherosclerosis in apoE-null mice by about 60%. Immunizations with these peptides were also found to increase the collagen content of subvalvular lesions.

Conclusions— These studies have identified peptide sequences in apoB-100 that induce immune responses, which inhibits atherosclerosis. This suggests a way of developing an immunization therapy for coronary heart disease.

Key Words: apolipoproteins • atherosclerosis • immunization • mice • peptides

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