Scale bars = 50m except for (D) where bar = 100m

Scale bars = 50m except for (D) where bar = 100m. == Discussion == The use of therapeutic agents targeting the arterial wall, especially those aimed at preventing the retention of proatherogenic lipoproteins in the subendothelial matrix, is a promising strategy which has been poorly addressed.14Previously, we reported that chP3R99 mAb prevents atherosclerosis in rabbits; presumably through the induction of autologous anti-CS antibodies generated upon immunization. with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis. Keywords:monoclonal antibodies, glycosaminoglycans, atherosclerosis, technetium-99m, imaging == Abbreviations == percentage of injected dose per gram of tissue Atherosclerotic rabbits chondroitin sulfate chondroitin sulfate proteoglycans dermatan sulfate enzyme-linked immunoadsorbent assay glycosaminoglycan low density lipoprotein monoclonal antibody Non atherosclerotic rabbit New Zealand White rabbits proteoglycans == Introduction == Atherosclerosis is the underlying pathology of most cardiovascular events and the main cause of morbidity and mortality worldwide.1This disease is characterized by a non-resolved inflammatory response triggered by the retention of apoB-containing lipoproteins in the artery wall.2,3Upon entrapment in the intima layer, proatherogenic lipoproteins undergo oxidative and enzymatic modifications thereby increasing their immunogenicity.4These modifications also trigger the uptake of lipoprotein by macrophages and vascular easy muscle cells, which leads to foam cells formation.4,5 Subendothelial retention of low density lipoprotein (LDL) is mediated by electrostatic interactions between positively charged residues on apolipoprotein B-100 (apoB-100) and negatively charged glycosaminoglycans (GAGs) chains on proteoglycans (PGs).6,7A prominent feature of Bz 423 atherosclerosis progression is the accumulation of chondroitin sulfate (CS) and dermatan sulfate (DS) PGs, accompanied by hyperelongation of GAGs side chains.8,9CSPG-LDL complexes have been detected in injured rabbit intima,10and they have also been isolated from human atherosclerotic lesions.11 In a previous work, we characterized the antiatherogenic properties of the chimeric mouse/human monoclonal antibody (mAb) chP3R99, which binds sulfated GAGs, inhibits LDL binding to CS, and abrogates LDL oxidation in vitro. Moreover, rabbits immunized with chP3R99 mAb showed reduced aortic arch lesions and no macrophage infiltration following short-term treatment with Lipofundin 20% (referred to as Lipofundin).12Similar results were observed in ApoE/mice fed with a high-fat high-cholesterol diet in which the administration of chP3R99 mAb reduced the total lesion area in more than 40%.13 In this paper, we demonstrated that chP3R99 mAb preferentially accumulates in rabbit atherosclerotic lesions, supporting the use of anti-GAGs antibodies for the detection and treatment of atherosclerosis. == Results == == chP3R99 mAb reactivity to rabbit atherosclerotic lesions == To evaluate the content of GAG in Rabbit Polyclonal to POLE4 the artery wall, aortic sections from normal and Lipofundin-treated rabbits were stained with Alcian Blue. As depicted inFigure 1, the amounts of GAGs increased in the aortic arch depending on the presence and size of the lesions. Particularly, immunohistochemistry revealed a Bz 423 high content of CS in Bz 423 the aortic lesions of Lipofundin-receiving rabbits, which results in a strong reactivity of chP3R99 mAb in these areas. A lower reactivity was observed in aortic sections from the control rabbits and in Type I AHA lesions, whereas the isotype-matched control (hR3 mAb) did not react with any of the aortic sections. == Physique 1. Bz 423 == chP3R99 mAb reactivity to Lipofundin-induced atherosclerotic plaque from rabbit aorta. GAGs were detected in the artery wall of normal and Lipofundin-treated rabbits by Alcian Blue staining and immunohistochemistry with CS-56 mAb (1 g/mL). Samples from normal aorta and sections corresponding to areas with early and advanced lesions were incubated with chP3R99 mAb or the Bz 423 isotype-matched control hR3 (2 g/mL). Original magnification X20. Scale bars = 100 m. == chP3R99 mAb accumulation in Lipofundin-induced lesions == The accumulation of chP3R99 mAb in atherosclerotic lesions in vivo was addressed by immunofluorescence upon.