4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice
Geoffrey D. Wool et al.
The FASEB Journal
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, G. D., Cabana, V. G., Lukens, J., Shaw, P. X., Binder, C. J., Witztum, J. L., Reardon, C. A., Getz, G. S. 4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice.