Role of sodium tungstate as a potential antiplatelet agent

PURPOSE: Platelet inhibition is a key strategy in the management of atherothrombosis. However, the large variability in response to current strategies leads to the search for alternative inhibitors. The antiplatelet effect of the inorganic salt sodium tungstate (Na(2)O(4)W), a protein tyrosine phosphatase 1B (PTP1B) inhibitor, has been investigated in this study. METHODS: Wild-type (WT) and PTP1B knockout (PTP1B(−/−)) mice were treated for 1 week with Na(2)O(4)W to study platelet function with the platelet function analyzer PFA-100, a cone-and-plate analyzer, a flat perfusion chamber, and thrombus formation in vivo. Human blood aliquots were incubated with Na(2)O(4)W for 1 hour to measure platelet function using the PFA-100 and the annular perfusion chamber. Aggregometry and thromboelastometry were also performed. RESULTS: In WT mice, Na(2)O(4)W treatment prolonged closure times in the PFA-100 and decreased the surface covered (%SC) by platelets on collagen. Thrombi formed in a thrombosis mice model were smaller in animals treated with Na(2)O(4)W (4.6±0.7 mg vs 8.9±0.7 mg; P<0.001). Results with Na(2)O(4)W were similar to those in untreated PTP1B(−)/(−) mice (5.0±0.3 mg). Treatment of the PTP1B(−)/(−) mice with Na(2)O(4)W modified only slightly this response. In human blood, a dose-dependent effect was observed. At 200 μM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T) decreased with Na(2)O(4)W. Neither the aggregating response nor the viscoelastic clot properties were affected. CONCLUSION: Na(2)O(4)W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na(2)O(4)W may be acting on platelet PTP1B, other potential targets should not be disregarded.