title: Antiatherosclerotic effect of an antibody that binds to extracellular matrix glycosaminoglycans.
abstract: OBJECTIVE
  Subendothelial retention of proatherogenic lipoproteins by proteoglycans is critical in atherosclerosis. The aim of this study was to characterize the recognition and antiatherogenic properties of a chimeric monoclonal antibody (mAb) that reacts with sulfated molecules.
  
  
  RESULTS
  chP3R99 mAb recognized sulfated glycosaminoglycans, mainly chondroitin sulfate (CS), by ELISA. This mAb blocked ≈70% of low-density lipoprotein (LDL)-CS association and ≈80% of LDL oxidation in vitro, and when intravenously injected to Sprague-Dawley rats (n=6, 1 mg/animal), it inhibited LDL (4 mg/kg intraperitoneally, 1 hour later) retention and oxidation in the artery wall. Moreover, subcutaneous immunization of New Zealand White rabbits (n=19) with chP3R99 mAb (100 μg, 3 doses at weekly intervals) prevented Lipofundin-induced atherosclerosis (2 mL/kg, 8 days) with a 22-fold reduction in the intima-media ratio (P<0.01). Histopathologic and ultrastructural studies showed no intimal alterations or slight thickening, with preserved junctions between endothelial cells and scarce collagen fibers and glycosaminoglycans. In addition, immunization with chP3R99 mAb suppressed macrophage infiltration in aorta and preserved redox status. The atheroprotective effect was associated with the induction of anti-CS antibodies in chP3R99-immunized rabbits, capable of blocking CS-LDL binding and LDL oxidation.
  
  
  CONCLUSIONS
  These results support the use of anti-sulfated glycosaminoglycan antibody-based immunotherapy as a potential tool to prevent atherosclerosis.
authors.affiliation: Center of Molecular Immunology, University of Havana, 216 St and 15th Ave, PO Box 16040, Atabey, Playa, Havana 11600, Cuba.
authors.forename: Yosdel
authors.initials: Y
authors.lastname: Soto
authors.forename: Emilio
authors.initials: E
authors.lastname: Acosta
authors.forename: Livan
authors.initials: L
authors.lastname: Delgado
authors.forename: Arlenis
authors.initials: A
authors.lastname: Pérez
authors.forename: Viviana
authors.initials: V
authors.lastname: Falcón
authors.forename: María A
authors.initials: MA
authors.lastname: Bécquer
authors.forename: Ángela
authors.initials: Á
authors.lastname: Fraga
authors.forename: Víctor
authors.initials: V
authors.lastname: Brito
authors.forename: Irene
authors.initials: I
authors.lastname: Álvarez
authors.forename: Tania
authors.initials: T
authors.lastname: Griñán
authors.forename: Yuniel
authors.initials: Y
authors.lastname: Fernández-Marrero
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Requena
authors.forename: Miriam
authors.initials: M
authors.lastname: Noa
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández
authors.forename: Ana María
authors.initials: AM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000918:Antibody Specificity; D050197:Atherosclerosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001692:Biological Transport; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000037:antagonists & inhibitors* / Q000276:immunology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000276:immunology; D007114:Immunization; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010743:Phospholipids; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol
chemical_list: D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D010743:Phospholipids; C099252:oxidized low density lipoprotein; C008288:Lipofundin; D013012:Sorbitol; D002809:Chondroitin Sulfates