title: Isolation and characterization of a heparin with low antithrombin activity from the body of Styela plicata (Chordata-Tunicata). Distinct effects on venous and arterial models of thrombosis.
abstract: BACKGROUND
  A heparin preparation with low antithrombin activity and different disaccharide composition than mammalian heparin was isolated from the body of the ascidian Styela plicata (Chordata-Tunicata). The disaccharide composition and the effect of the invertebrate glycan on venous and arterial models of thrombosis was investigated.
  
  
  RESULTS
  High performance liquid chromatography of the products formed by a mixture of heparin lyases showed that the ascidian heparin is composed mainly by delta UA(2SO4)-1-->4-beta-d-GlcN(SO4) (47.5%), delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(6SO4) (38.3%) disaccharides and smaller amounts of the disaccharides delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(3SO4)(6SO4) (2.8%) and delta UA(2SO4)-1-->4-beta-d-GlcN(SO4)(3SO4) (8.0%). The invertebrate heparin has an aPTT activity of 18 IU/mg and an antithrombin-mediated antithrombin and anti-factor Xa activities 10-fold lower than that of mammalian heparin. In a venous model of thrombosis in the vena cava, S. plicata heparin inhibits only 80% of thrombosis at a dose 10-fold higher than that of the mammalian heparin that inhibits 100% of thrombosis. However, in an arterio-shunt model of arterial thrombosis, both S. plicata and mammalian heparin possess equivalent antithrombotic activities. It is also shown that at equivalent doses, ascidian heparin has a lower bleeding effect than mammalian heparin.
  
  
  CONCLUSIONS
  The antithrombin-mediated anticoagulant activity of heparin polymers is not directly related to antithrombotic potency in the arterio-venous shunt. The results of the present work suggest that heparin preparations obtained from the body of S. plicata may have a safer therapeutic action in the treatment of arterial thrombosis than mammalian heparin.
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ, CEP 21941-590, Brazil.
authors.forename: Joana C
authors.initials: JC
authors.lastname: Santos
authors.forename: Juliana M F
authors.initials: JM
authors.lastname: Mesquita
authors.forename: Celso L R
authors.initials: CL
authors.lastname: Belmiro
authors.forename: Carolina B M
authors.initials: CB
authors.lastname: da Silveira
authors.forename: Christian
authors.initials: C
authors.lastname: Viskov
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Mourier
authors.forename: Mauro S G
authors.initials: MS
authors.lastname: Pavão
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification* / Q000627:therapeutic use; D000991:Antithrombins / Q000302:isolation & purification* / Q000627:therapeutic use; D006493:Heparin / Q000302:isolation & purification* / Q000627:therapeutic use; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy*; D014561:Urochordata / Q000737:chemistry*; D020246:Venous Thrombosis / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D006493:Heparin