Resistin Plays An Important Role On Platelet Function

BackgroundResistin is a newly-discovered protein antagonizing insulin sensitivity. Many researches have demonstrated that it was associated with insulin resistance, inflammation, the development of atherosclerosis and thrombotic diseases in metabolic syndrome. Platelets plays an important role on thrombus growth, contributing to the development of thrombotic diseases, such as, acute myocardial infarction, deep venous thrombosis and stroke. So far, there was no investigation on resistin affecting the platelet function. The present study was to approach whether and how resistin affect platelet function, and if it play the role through p38 MAPK, ERK or TLR-4 signaling pathways.MethodsThe platelet-rich plasma from 8 healthy human volunteers were pre-incubated with different concentrations of resistin, with or without ADP (10uM), or thrombin (0.05U/ml), or pre-treated with inhibitors prior to resistin treatment. Maximum platelet activation was determined by measuring the P-selectin expression on flow cytometry and clot retraction.ResultsResistin significantly elevated platelet activation. At 50ng/ml, the P-selectin exprosure was 48.02±7.61%, which was the highest. Platelet activation stimulated by resistin (50ng/ml) was similar to ADP (10uM), the P-selectin levels were 51.74±5.2% vs 52.96±2.88%, P=0.621, whereas stronger than thrombin (0.05U/ml) (51.74±5.2% vs 45.08±2.7%, P=0.028).Co-incubated the platelets with resistin (50ng/ml) and ADP, didn't further stimulate P-selectin expression significantly (52.96±2.88% vs 55.51±3.91%, P=0.203). In contrast, the platelet expression of P-selectin was further enhanced by co-incubated with resistin and thrombin (45.08±2.7% vs 50.41±3.59%, P=0.02). SB203580 significantly attenuated resistin 's upregulation on P-selectin expression (25.22±8.34% vs 51.74±5.2%, P<0.001), while PD98059 and Anti-TLR4 antibody did not affect the platelet activation by resistin. ConclusionTaken together, our data demonstrated that resistin may directly affect the platelet function by stimulating P-selectin through the p38 MAPK signaling pathway, suggesting that high level of resistin in metabolic syndrome patients may accelerate thrombosis development by platelet activation.