Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice
Braz. j. med. biol. res
; 41(12): 1086-1092, Dec. 2008. ilus, graf
Article
in En
| LILACS
| ID: lil-502158
Responsible library:
BR1.1
ABSTRACT
In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each) mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized 1.0 ± 1.4; control 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized 4.7 ± 2.7; control 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized 2.3 ± 1.5; control 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized 0.30 ± 0.020; control 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.
Key words
Full text:
1
Index:
LILACS
Main subject:
Immunoglobulin G
/
Receptors, LDL
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Immunization, Passive
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Atherosclerosis
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Lipoproteins, LDL
/
Antibodies, Monoclonal
Limits:
Animals
Language:
En
Journal:
Braz. j. med. biol. res
Journal subject:
BIOLOGIA
/
MEDICINA
Year:
2008
Type:
Article
/
Project document