title: The treatment with an anti-glycosaminoglycan antibody reduces aortic oxidative stress in a rabbit model of atherosclerosis.
abstract: Retained low-density lipoproteins (LDL) by arterial glycosaminoglycans (GAG) are more susceptible to reactive oxygen species-mediated oxidation, contributing to oxidative stress and atherosclerosis. Recently, we reported the properties of the chimeric mouse/human monoclonal antibody chP3R99-LALA to bind sulfated GAG, to inhibit LDL-chondroitin sulfate binding, and to avoid LDL oxidation in vitro. Here, we hypothesized that chP3R99-LALA treatment might reduce aortic oxidative stress in a therapeutic setting. Redox biomarkers and serum lipids were determined by spectrophotometric methods. Subcutaneous administration of five doses (100 μg) of chP3R99-LALA, after Lipofundin administration (2 mL/kg/day, i.v.) during 8 days, reduced atherosclerotic lesion development, which was not associated with a serum lipid modulation. In contrast, the treatment with chP3R99-LALA reduced (p < 0.05) malondialdehyde and protein oxidation, induced a restoration of reduced glutathione level, of the superoxide dismutase and catalase activities and of endothelial nitric oxide level. Thus, the antiatherogenic effect of chP3R99-LALA treatment seems to be associated with a reduction of aortic oxidative stress. These results contribute in understanding the molecular mechanisms associated with chP3R99-LALA atheroprotection and support the use of anti-GAG antibody-based immunotherapy as a potential tool to treat the atherosclerosis.
authors: Center of Studies for Research and Biological Evaluations, Pharmacy and Food Sciences College, University of Havana, Havana, Cuba.
authors: L
authors: L
authors: Delgado-Roche
authors: E
authors: E
authors: Acosta
authors: Y
authors: Y
authors: Soto
authors: Y
authors: Y
authors: Hernández-Matos
authors: A
authors: A
authors: Olivera
authors: E
authors: E
authors: Fernández-Sánchez
authors: A M
authors: AM
authors: Vázquez
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006025:Glycosaminoglycans / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000888:Antibodies, Anti-Idiotypic; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein