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. 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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Blocking LDL retention with antibodies against sulfated glycosaminoglycans of proteoglycans decreases LDL modification and atherosclerosis.
“blocking of LDL retention with antibodies generated against the sulfated glycosamino-glycans of proteoglycans decreases LDL modification and atherosclerosis48.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [48]
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Hellberg, S., Ahmed, O., Zhang, Y., Nunzio, G. D., Björck, H. M., Francis, R., Fagerberg, L., Gisterå, A., Zhang, X., Metso, J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.13.512086 · Cited by 1 · see citing works
Self-citationInhibition of macrophage metabolism by oxLDL
Katouah, H. A. (2012) · UC Research Repository (University of Canterbury) · doi:10.26021/6511
Delgado-Roche, L., Acosta, E., Soto, Y., Hernández-Matos, Y., Bécquer, M. A., Álvarez, D., Fernández-Sánchez, E. M., Vázquez, A., & Delgado-Roche, C. L. (2015) · Revista de Ciencias Farmacéuticas y Alimentarias
Self-citationDelgado-Roche, L., Hernández-Matos, Y., Simón, G. G., López, A. M., & Pardo‐Andreu, G. L. (2015) · Revista de Ciencias Farmacéuticas y Alimentarias
Lipid: Extracellular Matrix Interactions as Therapeutic Targets in the Atherosclerosis of Diabetes
Kamato, D., & Little, P. J. (2023) · Contemporary diabetes · doi:10.1007/978-3-031-26681-2_12
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Self-citationStudy on the Anti-Inflammatory Activity of Chondroitin Sulfate-Curcumin Amphiphilic Polymers
高, 继. (2025) · Hans Journal of Biomedicine · doi:10.12677/hjbm.2025.154081
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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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