lipoproteins in the artery wall, which would complement current therapies. Immunization with apoB100-derived peptides contain- ing one of the PG-binding sites has been considered a promising strategy to block LDL retention in vivo and consequently atherosclerotic development [7]. In addition, endostatin, a fragment of collagen type XVIII released by proteolysis, was shown to interfere with lipoprotein reten- tion in subendothelial matrix. Endostatin exerts antiath- erosclerotic effects mainly interfering with biglycan-LDL binding [8]. Also, imatinib, a platelet-derived growth fac- tor receptor inhibitor, has demonstrated to inhibit GAG synthesis on vascular PG and to reduce LDL binding in vitro and in vivo [9]. Recently, our group demonstrated that chP3R99 mono- clonal antibody (mAb) recognized arterial sulfated GAG; mainly chondroitin sulfate (CS). In vitro studies showed that chP3R99 blocked 70% of LDL-CS association and 80% of LDL oxidation. Also, this antibody inhibited the retention and oxidation of LDL in rat’ s arterial wall in vivo. Moreover, subcutaneous immunization of New Zealand White (NZW) rabbits with chP3R99 and its vari- ant with impaired Fc γ receptor (Fc γR) and complement binding (named chP3R99-LALA) prevented Lipofundin- induced atherosclerotic lesions in a preventive setting. On the other hand, the administration of chP3R99 suppressed The treatment with an anti-glycosaminoglycan antibody reduces aortic oxidative stress in a rabbit model of atherosclerosis L. Delgado-Roche 1 , E. Acosta 2 , Y. Soto 3 , Y. Hernández-Matos 1 , A. Olivera 4 , E. Fernández-Sánchez 1 & A. M. Vázquez 5 1 Center of Studies for Research and Biological Evaluations, Pharmacy and Food Sciences College, University of Havana, Havana, Cuba, 2 Department of Histopathology, Center of Advanced Studies, Havana, Cuba, 3 Immunobiology Direction, Center of Molecular Immunology, Havana, Cuba, 4 Department of Experimental Surgery, CIMEQ Hospital, Havana, Cuba, and 5 Innovation Managing Direction, Center of Molecular Immunology, Havana, Cuba 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 mono- clonal 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 Introduction Cardiovascular diseases are the main cause of morbidity and mortality in the developed countries and the athero- sclerosis is the underlying cause of most of these diseases [1]. The subendothelial retention of low-density lipopro- teins (LDL) is considered a key initiating process in atherogenesis [2,3]. Lipoprotein retention is mediated by the electrostatic interaction with extracellular matrix molecules, mainly glycosaminoglycans (GAG) present in arterial proteoglycans (PG). In the vasculature, reactive oxidant species, including reactive oxygen (ROS), nitro- gen, or halogenating species may oxidatively modify lipids and proteins with deleterious consequences for vascular function [4]. The retained LDL are more susceptible to the action of these biologically active free radical and nonradical species [5]. Oxidative-modified LDL possesses proinflammatory properties which contribute to the ath- erosclerosis development [4]. Despite the cholesterol-lowering effect and anti- inflammatory properties of statins, atherosclerosis contin- ues to progress in a significant proportion of patients [5]. On the other hand, antioxidants have failed in the primary and secondary prevention of cardiovascular diseases [6]. Thus, there is a widespread agreement on the need of therapies directed to avoid the retention of atherogenic Correspondence: Ana María Vázquez, PhD, Innovation Managing Direction, Center of Molecular Immunology, P.O. Box 16040, Havana, Cuba. Tel: + 537‐2143175. Fax: + 537‐2720644. E-mail: maruchi@cim.sld.cu (Received date: 12 December 2012; Accepted date: 31 January 2013; Published online: 27 February 2013) Free Radical Research, April 2013; 47(4): 309–315 © 2013 Informa UK, Ltd. ISSN 1071-5762 print/ISSN 1029-2470 online DOI: 10.3109/10715762.2013.772995 ORIGINAL ARTICLE Free Radic Res Downloaded from informahealthcare.com by Mr Jörgen Granroth on 03/14/13 For personal use only.