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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Basic sciences department, Isfahan Cardiovascular Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. sasgary@yahoo.com
Sedigheh
S
Asgary
Salb-Ali
SA
Saberi
Shirin
S
Azampanah
D000818:Animals; D000941:Antigens / Q000737:chemistry; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D004032:Diet; D006937:Hypercholesterolemia / Q000150:complications; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008297:Male; D010100:Oxygen / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D014611:Vaccination
D000941:Antigens; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003300:Copper; D010100:Oxygen