Cargando…

Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives

The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin...

Descripción completa

Detalles Bibliográficos
Autores principales: Vasconcelos, Ariana A., Sucupira, Isabela D., Guedes, Alessandra L., Queiroz, Ismael N., Frattani, Flavia S., Fonseca, Roberto J., Pomin, Vitor H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163371/
https://www.ncbi.nlm.nih.gov/pubmed/30200211
http://dx.doi.org/10.3390/md16090304
_version_ 1783359344992059392
author Vasconcelos, Ariana A.
Sucupira, Isabela D.
Guedes, Alessandra L.
Queiroz, Ismael N.
Frattani, Flavia S.
Fonseca, Roberto J.
Pomin, Vitor H.
author_facet Vasconcelos, Ariana A.
Sucupira, Isabela D.
Guedes, Alessandra L.
Queiroz, Ismael N.
Frattani, Flavia S.
Fonseca, Roberto J.
Pomin, Vitor H.
author_sort Vasconcelos, Ariana A.
collection PubMed
description The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.
format Online
Article
Text
id pubmed-6163371
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61633712018-10-11 Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives Vasconcelos, Ariana A. Sucupira, Isabela D. Guedes, Alessandra L. Queiroz, Ismael N. Frattani, Flavia S. Fonseca, Roberto J. Pomin, Vitor H. Mar Drugs Article The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities. MDPI 2018-08-30 /pmc/articles/PMC6163371/ /pubmed/30200211 http://dx.doi.org/10.3390/md16090304 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vasconcelos, Ariana A.
Sucupira, Isabela D.
Guedes, Alessandra L.
Queiroz, Ismael N.
Frattani, Flavia S.
Fonseca, Roberto J.
Pomin, Vitor H.
Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_full Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_fullStr Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_full_unstemmed Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_short Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
title_sort anticoagulant and antithrombotic properties of three structurally correlated sea urchin sulfated glycans and their low-molecular-weight derivatives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163371/
https://www.ncbi.nlm.nih.gov/pubmed/30200211
http://dx.doi.org/10.3390/md16090304
work_keys_str_mv AT vasconcelosarianaa anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT sucupiraisabelad anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT guedesalessandral anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT queirozismaeln anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT frattaniflavias anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT fonsecarobertoj anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives
AT pominvitorh anticoagulantandantithromboticpropertiesofthreestructurallycorrelatedseaurchinsulfatedglycansandtheirlowmolecularweightderivatives