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.

Keywords::

• atherosclerosis
• glycosaminoglycans
• oxidative stress
• monoclonal antibody

Acknowledgements

The authors want to thank the technical assistance of Dalia R. Álvarez, Milagros Frómeta and María A. Bécquer. Also we acknowledge the support from the Center of Molecular Immunology, Cuba.

Disclosures

Dr. Vázquez is an inventor of patents related with antibodies that recognize sulfatides and sulfated proteoglycans; however, she has signed the assignment of her rights to the assignee Center of Molecular Immunology.