title: Is the antithrombotic effect of sulfated galactans independent of serpin?
abstract: BACKGROUND
  Sulfated galactans are polysaccharides with heterogeneous structures that frequently show anticoagulant activity. Their anticoagulant mechanisms are complex and distinct from those observed for heparin. Sulfated galactans act through a combination of effects involving serpin-dependent and serpin-independent mechanisms. Interestingly, these polymers can also induce blood coagulation due to activation of factor XII (FXII).
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: A-L G
authors.initials: AL
authors.lastname: Quinderé
authors.forename: G R C
authors.initials: GR
authors.lastname: Santos
authors.forename: S-N M C G
authors.initials: SN
authors.lastname: Oliveira
authors.forename: B F
authors.initials: BF
authors.lastname: Glauser
authors.forename: B P
authors.initials: BP
authors.lastname: Fontes
authors.forename: I N L
authors.initials: IN
authors.lastname: Queiroz
authors.forename: N M B
authors.initials: NM
authors.lastname: Benevides
authors.forename: V H
authors.initials: VH
authors.lastname: Pomin
authors.forename: P A S
authors.initials: PA
authors.lastname: Mourão
mesh_terms: D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D002852:Chromatography, Ion Exchange; D005685:Galactans / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015843:Serpins / Q000502:physiology*; D013431:Sulfates / Q000737:chemistry*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D005685:Galactans; D015843:Serpins; D013431:Sulfates
keywords: anticoagulant drugs; antithrombotic agents; bleeding; coagulation factor XII; heparin sodium