Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences
Autor: | Marie W. Lindholm, Gunilla Nordin Fredrikson, Paul C. Dimayuga, Jan Nilsson, Kuang-Yuh Chyu, Ingrid Söderberg, Prediman K. Shah |
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Rok vydání: | 2003 |
Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Apolipoprotein B Arteriosclerosis Hypercholesterolemia Molecular Sequence Data Aorta Thoracic Autoantigens Mice Apolipoproteins E Immune system Peptide Library Malondialdehyde Internal medicine medicine Animals Amino Acid Sequence Peptide library Peptide sequence Triglycerides Apolipoproteins B Mice Knockout biology business.industry Macrophages medicine.disease Peptide Fragments Lipoproteins LDL Mice Inbred C57BL Endocrinology Immunization Apolipoprotein B-100 Immunology biology.protein Diet Atherogenic lipids (amino acids peptides and proteins) Collagen Antibody Cardiology and Cardiovascular Medicine business |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 23:879-884 |
ISSN: | 1524-4636 1079-5642 |
DOI: | 10.1161/01.atv.0000067937.93716.db |
Popis: | 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. |
Databáze: | OpenAIRE |
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