Abstract 14340: Intraperitoneal Administration of Low Dose 2s, Apoa-i Mimetic Peptide, Inhibits The Atherosclerotic Lesion Development in Apoe−/− Mice
Background and aim: Not only HDL injection but also apoA-I mimetic peptide can be developed as the effective medicine in the treatment of acute coronary syndrome. We have generated apoA-I mimetic peptide named 2s, which is structurally similar to 4F but two F sites of 4 phenylalanines were replaced with two non-natural amino acid analogs and investigated its effect as therapeutic drug for atherosclerosis using apoE−/− mice.
Methods: ApoE−/− mice (10 mice/group) at 6 weeks of age were fed with 0.15% high fat high cholesterol diet (HFHC) for 8 weeks and the diet was changed to normal chow diet and was continued for another 4 weeks. Mice were injected intraperitonealy with 2s and 4F peptides at doses of 1mg/kg or 20mg/kg, three times a week during the last 4 weeks. Mice receiving saline or water without peptides were used as reference group. After 12 weeks, mice were sacrificed and atherosclerotic lesions in aorta and aortic sinus were examined by oil red O staining and immunohistochemistry.
Results: Lipid accumulation in aorta was reduced by 39% (p<0.001) and 25% (p<0.001) in 2s treated group but by 8% (p=0.11) and 24% (p=0.52) in 4F treated group at doses of 1 and 20 mg/kg, respectively. Lipid accumulation in aortic sinus was reduced by 44% (p<0.01) and 47% (p<0.01) in 2s treated group but by 28% (p=0.39) and 13% (p<0.01) in 4F treated group at doses of 1 and 20 mg/kg, respectively. MOMA staining revealed that monocytes infiltration in 2s treated group was dramatically reduced by 54% (p<0.05) and 67% (p<0.01) but it is shown to increase by 8% (p=0.77) and 17% (p=0.58) in 4F treated group at doses of 1 and 20 mg/kg, respectively. No significant changes in lipid levels but liver enzymes were noted to decrease in both 2s and 4F treated groups. 2s peptide directly binded to SRB1 and enhanced cholesterol efflux. It also inhibited smooth muscle cell proliferation.
Conclusions: ApoA-I mimetic peptide, 2s, effectively stabilized or decreased atherosclerotic lesion, monocytes infiltration in HFHC-fed ApoE−/− mice. 2s peptide might be developed as a therapeutic reagent for the treatment of atherosclerotic diseases.
- © 2011 by American Heart Association, Inc.