Effect of immunization against ox-LDL with two different antigens on formation and development of atherosclerosis

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Several studies were pointed to oxidized LDL (ox-LDL) as one of the main immunogenes which have important roles in primary lesions of atherosclerosis. In this study, by immunization against ox-LDL with two different antigens in an animal model (rabbit) and consideration of its effect on two different dietary regimens; we tried to clear relation between immune system and atherosclerosis.


LDL was isolated from hypercholesterolemic rabbits plasma and oxidized with MDA or Cu++. Rabbits were divided to three groups and immunized with MDA-LDL or Cu-LDL or phosphate-buffer (PBS) as a control group. Immunization was repeated after 2, 4, 6, and 8 weeks and concentration of antibodies against ox-LDL was measured in each stage. After immunization, rabbits in each group were divided to two subgroups based on the dietary regimen (fed normal or high cholesterol diet). At the beginning and the end of the study, biochemical factors were measured. Also, fatty streaks in aorta and left and right coronary arteries evaluated.

Immunization with Cu2+-LDL and MDA-LDL induced statistically significant antibodies against ox-LDL. In hypercholesterolemic rabbits immunized with MDA-LDL the level of cholesterol, LDL-cholesterol, triglyceride, fasting blood sugar and fatty streak lesions in aorta and right coronary arteries were significantly decreased as compared with non-immunized high-cholesterol group. Immunization with Cu2+-LDL in hypercholesterolemic rabbits significantly decreased triglyceride, fasting blood sugar, cholesterol and CRP. No significant differences were detected in the fatty streak lesions in this group as compared with non-immunized high-cholesterol diet. In groups under normal diet immunized with MDA-LDL or Cu2+-LDL no significant effect on biochemical factors and atherosclerotic lesions were observed.

This study indicates that although the effect of produced antibodies in several methods and different dietary regimens is different, immunization against ox-LDL is antiatherogenic.

In the recent studies, relation between immune system and atherosclerosis has been investigated [1-3]. It is clear that this system can be effective on severity of atherosclerosis through different immunogenic mechanisms [4-6]. Several studies were pointed to oxidized LDL (ox-LDL) as one of the main immunogenes which have important roles in primary lesions of atherosclerosis [5,6]. Little changes in LDL strongly converted it to immunogenic particle. ox-LDL is a toxic particle that stimulates several cellular and humeral responses [7]. The existence of activated macrophages against ox-LDL in atherosclerotic lesions is a marker for primary cellular responses [8]. Different types of antibodies against ox-LDL were recognized in blood stream. These antibodies are measured in both human and animal models [9-12] bind to ox-LDL epitopes and cause atherosclerosis. As, hypercholesterolemic rabbits immunized with homologous, ox-LDL have a markedly reduced neointimal area after balloon injury despite sever hypercholesterolemia, then immunization against atherosclerosis also is a target to prevent restenosis and further investigation in this field is warranted [13].


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