Background: Several studies were pointed to oxidized LDL (OX-LDL) as one of the main immunogenic agents which have important roles in primary lesions of atherosclerosis. In this study, via immunization against OX-LDL with two different antigens in an animal model (rabbit); we tried to clear relation between immune system and atherosclerosis. 

Methods: LDL was isolated from healthy human plasma and oxidized with MDA or Cu⁺⁺. Rabbits were divided to three groups and after 2 weeks (under basic diet) immunized with MDA-LDL or Cu-LDL. In control group Phosphate-buffered saline (PBS) was used. Immunization was repeated with these materials again the weeks of 2, 4, 6, and 8 and concentration of OX-LDL antibody was measured in each stage. At the end of 8^th week, rabbits fed normal or high cholesterol regimens. Biochemical factors were measured at the beginning and end of study, also Fatty streaks in aorta and left and right coronary arteries was evaluated.

Results: Immunization with Cu -LDL and MDA-LDL induced adequate antibody formation (IgG) at the end of 8^th weeks. Immunization with MDA-LDL significantly decreased the level of cholesterol, LDL-cholesterol and fasting blood sugar (FBS) (P= 0.04). Also a significant decrease in fatty streak lesions was detected in aorta and right and left coronary arteries as compared with non-immunized high-cholesterol group (P= 0.04). Immunization with Cu -LDL significantly decreased Triglyceride, FBS and cholesterol as compared with non-immunized high cholesterol. No differences were detected in the fatty streak lesions in this group as compared with non-immunized high-cholesterol diet cu⁺²-LDL immunized group, shown significant decrease in CRP as compared with both non-immunized group and high cholesterol diet.

Conclusion: We conclude the protective effects of immune responses on atherosclerosis depend to what kind of antibody, so MDA-LDL and CU-LDL prevent atherosclerosis with different mechanism.