Antithrombotic and anticomplementary properties of a very low molecular mass dermatan sulfate.
BACKGROUND
Dermatan sulfate, a sulfated glycosaminoglycan, acts as an anticoagulant by accelerating the inhibition of thrombin by heparin cofactor II.


METHODS
A low molecular mass dermatan sulfate was obtained by peroxy-radical depolymerization from a parent dermatan sulfate. Chemical characterization of this low molecular mass dermatan sulfate shows a material of approximately 5 kDa that conserves sulfated sequences (2-O-sulfation of the iduronic acid units and/or 4 or 6 positions of galactosamina N acetyl) essential for dermatan sulfate-heparin cofactor II interaction with more sulphated proportion (27.7+/-1.9 microg% vs 11.5+/-0.8 microg%, P<0.05 n=6, low molecular mass dermatan sulfate vs dermatan sulfate).


RESULTS
After a single intravenous administration of low molecular dermatan sulfate in rats, fibrinolytic activity increased simultaneously with thrombin clotting time prolongation. Low molecular dermatan sulfate showed an inhibitory effect on classical complement activation pathway reaching a maximum during the first hour. Furthermore, low molecular dermatan sulfate was as effective as dermatan sulfate to prevent thrombus formation and to diminish thrombus weight in a rat venous thrombosis model.


CONCLUSIONS
The results indicate that peroxy-radical depolymerization of dermatan sulfate produced a low molecular dermatan sulfate with profibrinolytic, thrombolytic, antithrombotic and anticomplement properties. We conclude that low molecular dermatan sulfate may be an effective adjunct in the management of thrombotic events.
Fabiana Alberto
María
M
Academia Nacional de Medicina, Avenida Las Heras 3092, (C1425AUM) Ciudad Autónoma de Buenos Aires, Argentina.
Giaquinta Romero
Diego
D
Lazzari
María
M
Calabrese
Graciela C
GC
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D003165:Complement System Proteins / Q000378:metabolism; D003871:Dermatan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006461:Hemolysis; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D003871:Dermatan Sulfate; D003165:Complement System Proteins; D013917:Thrombin