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An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases.
Thromb Haemost. 2008 Mar; 99(3):531-8.TH

Abstract

Sulfated galactan from the red alga Botryocladia occidentalis has a potent anticoagulant activity, due to its ability to enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. It is less active than unfractionated heparin in arterial thrombosis, but in a venous thrombosis presents a dual effect, inhibiting thrombosis in low but not in high doses. This dual effect on venous thrombosis is a consequence of two actions, one that inhibits thrombin and factor Xa and one that induces factor XII activation. In order to dissociate these effects, we prepared derivatives of the sulfated galactan with low molecular weights. Two fractions that were similar in size to unfractionated heparin and low-molecular-weight heparin were obtained. As the molecular weight decreased, the ability to activate factor XII and to promote inhibition of coagulation proteases in the presence of antithrombin and heparin cofactor II diminished. At approximately 5 kDa, the sulfated galactan fragment had no effect on factor XII activation, and showed the same effect as unfractionated heparin in a venous thrombosis model. The approximately 5-kDa fragment is an antithrombotic with several advantages: i) It is as active as unfractionated heparin in venous thrombosis, but it has little activity in arterial thrombosis; ii) It inhibits venous thrombosis with very little anticoagulant effect; iii) It does not cause bleeding; and iv) It is not obtained from mammals.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Melo FR
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Mourão PA
No affiliation info available

MeSH

AnimalsAnticoagulantsAntithrombinsBleeding TimeBlood CoagulationBlood Coagulation TestsDisease Models, AnimalDose-Response Relationship, DrugFactor XIIaFactor XaFactor Xa InhibitorsFemaleFibrinolytic AgentsGalactansHemorrhageHeparinHeparin Cofactor IIHumansMaleMolecular WeightProtease InhibitorsRatsRats, WistarRhodophytaSulfatesThrombinThrombosisVenous Thrombosis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18327401

Citation

Melo, Fábio R., and Paulo A S. Mourão. "An Algal Sulfated Galactan Has an Unusual Dual Effect On Venous Thrombosis Due to Activation of Factor XII and Inhibition of the Coagulation Proteases." Thrombosis and Haemostasis, vol. 99, no. 3, 2008, pp. 531-8.
Melo FR, Mourão PA. An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases. Thromb Haemost. 2008;99(3):531-8.
Melo, F. R., & Mourão, P. A. (2008). An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases. Thrombosis and Haemostasis, 99(3), 531-8. https://doi.org/10.1160/TH07-10-0649
Melo FR, Mourão PA. An Algal Sulfated Galactan Has an Unusual Dual Effect On Venous Thrombosis Due to Activation of Factor XII and Inhibition of the Coagulation Proteases. Thromb Haemost. 2008;99(3):531-8. PubMed PMID: 18327401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor XII and inhibition of the coagulation proteases. AU - Melo,Fábio R, AU - Mourão,Paulo A S, PY - 2008/3/11/pubmed PY - 2008/5/16/medline PY - 2008/3/11/entrez SP - 531 EP - 8 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 99 IS - 3 N2 - Sulfated galactan from the red alga Botryocladia occidentalis has a potent anticoagulant activity, due to its ability to enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. It is less active than unfractionated heparin in arterial thrombosis, but in a venous thrombosis presents a dual effect, inhibiting thrombosis in low but not in high doses. This dual effect on venous thrombosis is a consequence of two actions, one that inhibits thrombin and factor Xa and one that induces factor XII activation. In order to dissociate these effects, we prepared derivatives of the sulfated galactan with low molecular weights. Two fractions that were similar in size to unfractionated heparin and low-molecular-weight heparin were obtained. As the molecular weight decreased, the ability to activate factor XII and to promote inhibition of coagulation proteases in the presence of antithrombin and heparin cofactor II diminished. At approximately 5 kDa, the sulfated galactan fragment had no effect on factor XII activation, and showed the same effect as unfractionated heparin in a venous thrombosis model. The approximately 5-kDa fragment is an antithrombotic with several advantages: i) It is as active as unfractionated heparin in venous thrombosis, but it has little activity in arterial thrombosis; ii) It inhibits venous thrombosis with very little anticoagulant effect; iii) It does not cause bleeding; and iv) It is not obtained from mammals. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/18327401/An_algal_sulfated_galactan_has_an_unusual_dual_effect_on_venous_thrombosis_due_to_activation_of_factor_XII_and_inhibition_of_the_coagulation_proteases_ DB - PRIME DP - Unbound Medicine ER -