Cited by 113Proteoglycans and glycosaminoglycans researchSeaweed-derived Bioactive CompoundsBlood Coagulation and Thrombosis Mechanisms

Sulfation pattern of the fucose branch is important for the anticoagulant and antithrombotic activities of fucosylated chondroitin sulfates

Chen, Shiguo, Li, Guoyun, Wu, Nian, Guo, Xin, Liao, Ningbo, Ye, Xingqian, Liu, Donghong, Xue, Changhu +1 more·2013·Biochimica et Biophysica Acta (BBA) - General Subjects

Abstract

Background The aim is to compare the structures, anticoagulant and antithrombotic activities of two fucosylated chondroitin sulfates isolated from sea cucumbers Isostichopus badionotus (fCS-Ib) and Pearsonothuria graeffei (fCS-Pg), which were known to have different sulfation patterns on the fucose branches.Methods The structures of fCSs were identified using 2D NMR. Anticoagulant activities were measured by activated partial thromboplastin time (APTT) and thrombin time (TT), and inhibition of factors IIa, Xa and XIIa was assessed in vitro. Antithrombotic activity was determined ex vivo by measuring the length and weight of the thrombus generated.Results The two fCSs had identical chondroitin sulfate E backbones and similar fucose branches, but different sulfation patterns of the fucose branches. The fucose branch in fCS-Ib was mainly 2,4-O-sulfated whereas that in fCS-Pg was mainly 3,4-O-sulfated. In vitro assay indicated that fCS-Pg possessed much lower potency than fCS-Ib in prolonging APTT/TT and in inhibition of thrombin. However, they both exhibited similar inhibitory effects on factor X activation by intrinsic tenase complex, and on thrombus generation. Furthermore, both fCSs significantly activated factor XII, which has been proved to be associated with adverse clinical events associated with heparin contaminated by oversulfated chondroitin sulfate.Conclusion The 2,4-O-sulfated fucose branch is the key structural factor of fCSs for prolonged APTT/TT and inhibition of thrombin, whereas the inhibitory effect of fCSs on factor X, XII activation and thrombus generation was attributed to the overall structure of fCS polysaccharide. GENERAL IMPORTANCE: Both fCSs have well defined structures and can be readily quality-controlled, and therefore may be potential alternatives for heparin as anticoagulant and antithrombotic drugs.

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Crossref · 10.1016/j.bbagen.2013.01.001

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  • Polysaccharides from marine animals demonstrate diverse biological properties, including anticoagulant, antithrombotic, antioxidative, neuroprotective, and antiviral activity.

    “These compounds demonstrate diverse biological properties, including anticoagulant and antitrombotic [131,132,133], antioxidative [134], neuroprotective [135,136], and antiviral activity as well [8,137].”

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Authors
Chen, S., Li, G., Wu, N., Guo, X., Liao, N., Ye, X., Liu, D., Xue, C., & Chai, W.
Affiliations
  • Zhejiang University (CN)
  • Ocean University of China (CN)
  • Imperial College London (GB)
Corresponding author
  • Ye, Xingqian
  • Xue, Changhu
Venue
Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher
Elsevier BV
Published
2013-04
Volume
1830
Issue
4
Pages
3054-3066
ISSN
0304-4165 (ISSN-L)
OpenAlex
W1968205748
Cited by
113
References
37
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 16 · 2018: 13 · 2017: 15 · 2016: 8 · 2015: 5 · 2014: 13 · 2013: 6
FWCI
6.19
Type
journal article
Language
en
Open access
closed
Locations
  • Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
fucosylated chondroitin sulfate, anticoagulant activity, antithrombotic activity, Isostichopus badionotus, factor Xa inhibition, factor XII activation, thrombin inhibition, heparin alternatives, thrombus formation
MeSH terms
Adult, Animals, Anticoagulants, Chondroitin Sulfates, Factor XII, Fibrinolytic Agents, Humans, Male, Magnetic Resonance Spectroscopy, Sea Cucumbers, Factor Xa Inhibitors

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