Abstract | BACKGROUND: OBJECTIVES: The structure of a complex sulfated galactan from the red alga Acanthophora muscoides was characterized by solution nuclear magnetic resonance. This polysaccharide and another previously characterized algal sulfated galactan from Botryocladia occidentalis were each used in in vitro and in vivo anticoagulant and antithrombotic assays to understand the possible structural determinants of their functional effects. RESULTS AND CONCLUSIONS: The serpin-dependent anticoagulant effects and FXII-related procoagulant effects of the sulfated galactans decreased in parallel with the molecular size. The serpin-independent anticoagulation also correlated with the chemical structure of the sulfated galactans. The sulfated galactan from A. muscoides, which showed mostly serpin-independent anticoagulant activity and reduced activation of FXII, drastically reduced arterial thrombus formation. However, the sulfated galactans produced opposite effects on venous thrombosis; this difference appears to result from the tenuous balance between the various effects on coagulation, including serpin-dependent and serpin-independent anticoagulation and FXIIa-dependent procoagulation. This study of novel sulfated polysaccharides with distinct effects on coagulation and thrombosis helps to establish the minimal structural-function relationship required for the development of antithrombotic drugs.
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Authors | A-L G Quinderé, G R C Santos, S-N M C G Oliveira, B F Glauser, B P Fontes, I N L Queiroz, N M B Benevides, V H Pomin, P A S Mourão |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 12
Issue 1
Pg. 43-53
(Jan 2014)
ISSN: 1538-7836 [Electronic] England |
PMID | 24261511
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 International Society on Thrombosis and Haemostasis. |
Chemical References |
- Anticoagulants
- Antithrombins
- Galactans
- Serpins
- Sulfates
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Topics |
- Anticoagulants
(chemistry, pharmacology)
- Antithrombins
(chemistry, pharmacology)
- Chromatography, Ion Exchange
- Galactans
(chemistry, pharmacology)
- Magnetic Resonance Spectroscopy
- Serpins
(physiology)
- Sulfates
(chemistry)
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