Differential effects of sodium spirulan on the secretion of fibrinolytic proteins from vascular endothelial cells: Enhancement of plasminogen activator activity

Abstract

Sodium spirulan (Na-SP) is a sulfated polysaccharide with Mr ∼220000 isolated from the blue-green alga Spirulina platensis. Na-SP influences the blood coagulation-fibrinolytic system by activation of heparin co-factor II in vitro, although it has been incompletely understood whether the polysaccharide can act on vascular endothelial cell functions. In the present study, we investigated the effects of Na-SP on the fibrinolytic activity of human coronary endothelial cells in a culture system. It was found that Na-SP enhances the activity of tissue-type and urokinase-type plasminogen activators in the conditioned medium of the cells through induction of urokinase-type plasminogen activator secretion and inhibition of plasminogen activator inhibitor type 1 (PAI-1) secretion. The inhibitory effect of Na-SP on PAI-1 secretion was maintained even when sodium ion was removed or replaced by calcium ion, while it disappeared with desulfation, indicating that metal ion is not required but the sulfate group is essential for the inhibition of endothelial PAI-1 secretion by Na-SP. The present study revealed that Na-SP not only shows a strong antithrombin effect through activation of heparin cofactor II but also exhibits a fibrinolytic property through differential effects on endothelial fibrinolytic protein secretion.