Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice

Autor(es)

D.M. Grosso ^[1] ; S. Ferderbar ^[2] ; A.C.B.A. Wanschel ^[3] ; M.H. Krieger ^[4] ; M.L. Higushi ^[5] ; D.S.P. Abdalla ^[6]

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas - Brasil

^[2] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas - Brasil

^[3] Universidade Estadual de Campinas. Instituto de Biologia. Departamento de Fisiologia e Biofísica - Brasil

^[4] Universidade Estadual de Campinas. Instituto de Biologia. Departamento de Fisiologia e Biofísica - Brasil

^[5] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil

^[6] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas. Departamento de Análises Clínicas e Toxicológicas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 41, n. 12, p. 1086-1092, 2008-12-00.

Resumo

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% 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. (AU)

• Processo FAPESP: 03/02435-2 - Efeito da imunizacao passiva com anticorpos monoclonais anti-ldl eletronegativa (ldl-) em camundongos knock out para receptor de ldl (ldlr-/-).
• Beneficiário: Daniela de Mattos Grosso
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado