Inhibition of atherosclerosis in apoE-null mice by immunization with apoB-100 peptide sequences.
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.


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.
Fredrikson
Gunilla Nordin
GN
Department of Medicine, Malmö University Hospital, Lund University, Malmö, Sweden. Gunilla.Nordin_Fredrikson@medforsk.mas.lu.se
Söderberg
Ingrid
I
Lindholm
Marie
M
Dimayuga
Paul
P
Chyu
Kuang-Yuh
KY
Shah
Prediman K
PK
Nilsson
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000276:immunology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000276:immunology / Q000517:prevention & control*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D003094:Collagen / Q000032:analysis; D004036:Diet, Atherogenic; D006937:Hypercholesterolemia / Q000235:genetics / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D014280:Triglycerides / Q000097:blood
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001324:Autoantigens; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D019151:Peptide Library; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D003094:Collagen