Abstract 10756: Resistin Stimulates Platelet P-selectin Expression via p38 MAPK Signal Pathway
Objection: Resistin is one of the important adipokines elevated in metabolic syndrome, closely associated with insulin resistance, inflammation, CHD and atherosclerosis. Yet reisitin’s regulation on platelet function and thrombosis development has not been revealed.
Methods: (1) Platelet-rich plasma (PRP) from 8 healthy human volunteers were pre-incubated with different concentrations of resistin, or pre-treated with MAPK signal pathway inhibitors prior to resistin treatment. Maximum platelet activation was determined in the presence of ADP (10uM), or thrombin (0.05U/ml). (2) Four weeks old C57BL/6 male mice were randomly grouped to receive intraperitoneal injection with either resistin (33ug/kg.d) or vehicle for 14 days, respectively. PRP obtained from mice were pre-incubated with or without resistin 30min prior to ADP activation. The effects of resistin on platelet function were examined by measuring the P-selectin expression with flow cytometry.
Results: (1) P-selectin levels of 50ng/ml resistin and 10uM ADP treated platelet were both significantly elevated (51.74±5.2%, 52.96±2.88% respectively vs. control 35.12±2.62%, p<0.05). (2) Thrombin also increased p-selectin levels significantly, which was further enhanced by resistin and thrombin coincubation, (50.41±3.59% vs.45.08±2.7%, P=0.02). Only P38 MAPK inhibitor SB203580 significantly attenuated resistin stimulated P-selectin expression on human platelets (25.22±8.34% vs 51.74±5.2%,P<0.001). (3) Platelet P-selectin levels of the mice treated with resistin for 2 weeks increased significantly compared to those of vehicle treated controls ( P<0.001, n=4). (4) Incubated the PRP with 50ng/ml resistin for 30min of vehicle-treated mice increased P-selectin markedly (P <0.05,n=4). (5) Resistin treatment significantly enhanced ADP stimulated P-selectin expression (P<0.001, n=4).
Conclusions: Resistin directly affects the platelet function and enhance thrombin stimulated P-selectin expression on human platelets through p38 MAPK signal pathway. Long term elevated levels of resistin significantly stimulate mice platelet activation, which may help to explore the mechanisms of prothrombotic state in patients with metabolic syndrome.
- © 2011 by American Heart Association, Inc.