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.
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.
Santos
Joana C
JC
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ, CEP 21941-590, Brazil.
Mesquita
Juliana M F
JM
Belmiro
Celso L R
CL
da Silveira
Carolina B M
CB
Viskov
Christian
C
Mourier
Pierre A
PA
Pavão
Mauro S G
MS
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
D000925:Anticoagulants; D000991:Antithrombins; D006493:Heparin