4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice.
Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F and 4F-Pro-4F (Pro), on nascent and mature atherosclerotic lesions and on levels of antibodies against oxidation-specific epitopes. Chow-fed apoE(-/-) mice were injected intraperitoneally with either the 4F peptide or a tandem helix apoA-I mimetic peptide (Pro) every other day. Mice treated with 4F, but not Pro, for 4 wk starting at 10 wk of age showed a dramatic decrease in atherosclerosis at 2 arterial sites. However, neither peptide was effective in mice treated for 8 wk starting at 20 wk of age; lesions were larger and more mature at this time point. Peptide treatment caused increased production of antibodies against oxidation-specific epitopes, including a disproportionate induction of the IgM natural antibody (NAb) E06/T15 to oxidized phospholipids. In summary, 4F, but not the tandem peptide Pro, effectively inhibited early atherogenesis but was ineffective against more mature lesions. Two different apoA-I mimetic peptides increased titers of natural antibodies against oxidation-specific epitopes.
Wool
Geoffrey D
GD
Department of Pathology, University of Chicago, Chicago, Illinois, USA.
Cabana
Veneracion G
VG
Lukens
John
J
Shaw
Peter X
PX
Binder
Christoph J
CJ
Witztum
Joseph L
JL
Reardon
Catherine A
CA
Getz
Godfrey S
GS
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000737:chemistry; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D000939:Epitopes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D000906:Antibodies; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D010455:Peptides; D000685:Serum Amyloid A Protein; C099252:oxidized low density lipoprotein; D043303:Aryldialkylphosphatase