In vivo and in vitro effects of low molecular weight heparan sulphate on the human fibrinolytic enzyme system.
The aim of this study was to evaluate the effects of a preparation of low molecular weight heparan sulphate (LMW-HS) on the fibrinolytic system. Twenty-five healthy volunteers received LMW-HS by mouth in three separate experiments. In the first experiment, 10 volunteers received either 80 mg LMW-HS or placebo in a single-blind cross-over study; blood samples were taken before and 1, 2, 3 and 6 h after treatment. LMW-HS caused an increase in global fibrinolysis, the effect being greatest after 2-3 h and disappearing by 6 h. However, neither plasminogen activator activity nor tissue-type plasminogen activator (tPA) antigen levels were changed. In the second experiment, daily doses of 80 mg LMW-HS were administered to 10 volunteers for 7 days; this regimen did not produce a statistically significant increase in fibrinolytic activity for the whole group although some individuals did respond markedly. In the third experiment, 160 mg LMW-HS administered to five volunteers did not affect ADP- and collagen-induced platelet aggregation. In vitro, LMW-HS added to plasma at concentrations of 20 and 30 micrograms/ml, brought about a significant increase in apparent plasminogen activator activity. These results suggest that the increased fibrinolytic activity seen after LMW-HS is due to the recruitment of additional amounts of tPA in the ex vivo test system. LMW-HS had no effect on plasminogen activator inhibitor.
Division of Biomedical Sciences, King's College London, Strand, UK.
N A
NA
Marsh
G V
GV
Born
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D003094:Collagen / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D010960:Plasminogen Activators / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000244:Adenosine Diphosphate; D003094:Collagen; D006497:Heparan Sulfate; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator