Effects Of Resistin Of Mice Platelet Function

BackgroundMetabolic syndrome (Mts), is a syndrome involves multiple metabolic disorders relatedintensely with cardiovascular diseases, especially obesity, hypertension, hyperglycemia anddyslipoproteinemia. A mass of clinical researches have showed a closely association of themetabolic syndrome with an increased risk of arterial and venous thromboembolism. Themechanism, however, has not been fully elucidated. Investigations have demonstrated thatvascular endothelial dysfunction, fibrinolysis inhibition and platelet activation were involved inthe pathological process of intravascular thrombus formation. Resistin is a recently discoveredadipokinine which is secreted by adipocytes and monocytes. It is not only associated withpathogenesis of insulin resistance, type 2 diabetes mellitus and obesity, but also is an importantvaso-active substance which can directly or indirectly affect the function of endothelial cells,cause local or systemic inflammation, participate in the formation and development of bloodclots. It is closely related to the adverse outcomes of cardiovascular diseases. Clinical studieshave showed that obesity is positively related to blood resistin concentration in patients withacute myocardial infarction, and resistin is likely to play a major role in the atherogenesis and itscomplications, and this action seems to be mostly related to the inflammatory reaction. Somestudies indicated that resistin could induce endothelial dysfunction by promotingendothelin-1(ET-1), intercellular adhesion molecule-1(ICAM-1), plasminogen activatorinhibitor-1 (PAI-1) release. However, whether resistin has effect on platelet function is far fromrevealed.ObjectiveThe purpose of the present study was to observe the effects of resistin on the plateletfunction in male C57BL/6 mice .Mehtods24 male C57BL/6 mice were divided into 3 experimental groups: normal saline treatedgroup (0.9%NS), resistin treated group (33.33ug/kg/day) and blank control group. Afterintraperitoneal injection for 2 weeks, platelet-rich plasma was obtained by centrifugation.Platelet-rich plasma was divided into 2 parts: (1) One part of the platelet-rich plasma was used to determine platelet activation by flow cytometry. (2) One part was used in clot retractionexperiment. The platelet-rich plasma of the blank group also was divided into 2 parts: (1) Onepart of the platelet-rich plasma was divided into 4 groups: controls, 10umol/L ADP treated group,50ng/mL resistin treated group, 10umol/L ADP and 50ng/mL resistin treated group. Aftertreatment respectively, platelet activation was determined by flow cytometry. (2) One part wasdivided into 2 groups: controls, 50ng/mL resistin treated group. After treatment respectively, theplatelet-rich plasma was used in clot retraction experiment.Results1. Short-term human recombined resistin stimulated the clot retraction (P<0.05);2. Long-term human recombined resistin stimulated the clot retraction (P<0.05);3. Short-term human recombined resistin effect increased the expression of P-selectin on plateletmembrane (P<0.05);4. Long-term human recombined resistin effect increased the expression of P-selectin on plateletmembrane (P<0.05);5. Human recombined resistin markedly up-regulated the expression of P-selectin on plateletmembrane induced by ADP (P<0.05).ConclusionHuman recombined resistin stimulated the clot retraction, as well as increased theexpression of P-selectin on platelet membrane. Resistin also enhanced ADP induced P-selectinupregulation, which, therefore, suggest that hight level of resistin may accelerate thrombosis byplatelet activation in metabolic syndrome.