Cited by 41Atherosclerosis and Cardiovascular DiseasesProteoglycans and glycosaminoglycans researchCholesterol and Lipid Metabolism

Antiatherosclerotic Effect of an Antibody That Binds to Extracellular Matrix Glycosaminoglycans

Soto, Yosdel, Acosta, Emilio, Delgado, Livan, Pérez, Arlenis, Falcón, Viviana, Bécquer, María A., Fraga, Ángela, Brito, Víctor +7 more·2012·Arteriosclerosis, Thrombosis, and Vascular Biology

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. Methods and 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. Conclusion—: These results support the use of anti-sulfated glycosaminoglycan antibody–based immunotherapy as a potential tool to prevent atherosclerosis.

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  1. Noa M, Mas R. Ateromisol y lesio ´n aterosclero ´tica en conejos inducida por Lipofundín. Progreso en Ciencias Me ´dicas Venezuela. 1992;6: 14 -19.

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Authors
Soto, Y., Acosta, E., Delgado, L., Pérez, A., Falcón, V., Bécquer, M. A., Fraga, Á., Brito, V., Álvarez, I., Griñán, T., Fernández-Marrero, Y., López-Requena, A., Noa, M., Fernández, E., & Vázquez, A. M.
Affiliations
  • Center of Molecular Immunology (Cuba) (CU)
  • From the Center of Molecular Immunology, Havana, Cuba (Y.S., A.P., V.B., T.G., Y.F.-M., A.L.-R., A.M.V.); Center of Studies for Research and Biological Studies, Pharmacy and Food Science College, University of Havana, Havana, Cuba (E.A., L.D., M.A.B., A.F., E.F.); Center for Genetic Engineering and Biotechnology, Havana, Cuba (V.F.); National Institute of Oncology and Radiobiology, Havana, Cuba (I.Á.); Center of National Products, National Center for Scientific Research, Havana, Cuba (M.N.).
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2012-03
Volume
32
Issue
3
Pages
595-604
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W2147399217
Cited by
41
References
59
Citations by year
2025: 3 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 4
FWCI
2.22
Type
journal article
Language
en
Open access
closed
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
atherosclerosis, chondroitin sulfate, sulfated glycosaminoglycans, monoclonal antibodies, immunotherapy, LDL oxidation, proteoglycans, extracellular matrix, macrophage infiltration, antiatherogenic effects, rabbit atherosclerosis model
MeSH terms
Animals, Antibodies, Monoclonal, Antibody Specificity, Biological Transport, Cell Line, Chondroitin Sulfates, Disease Models, Animal, Drug Combinations, Enzyme-Linked Immunosorbent Assay, Foam Cells, Glycosaminoglycans, Immunization, Lipoproteins, LDL, Oxidation-Reduction, Phospholipids, Rabbits, Sorbitol, Rats, Sprague-Dawley, Oxidative Stress, Atherosclerosis, Mice, Rats

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