Platelet activation and hyperresponsiveness in patients with Obesity

Obesity is characterized by a state of chronic low-grade inflammation with metabolic disorders. Studies have shown that an elevated prothrombotic state in which platelets are activated is observed in obesity. Alterations in platelet function resulting from metabolic disorders contribute to an elevated propensity for thrombus formation and arterial occlusion, increasing the high cardiometabolic risk. Nonetheless, the mechanisms of platelet activation and responsiveness in obesity remain poorly understood. Our hypothesis is that platelet activation in obesity contributes to tromboinflammation. To investigate that, platelets were isolated from obese and eutrophic individuals and analyzed for the platelet activation markers CD62P, CD63, PAC-1 and Tissue Factor (TF) by flow cytometry. The study was approved by the ethics committee 5.736.117. Our results showed a higher percentage of patients's activated platelets with surface expression of CD63, dense granules marker, and activated conformation αIIbβ3 integrin, but not CD62P (P-selectin) expression, compared to eutrophic controls. TF is a membrane glycoprotein that initiates the extrinsic pathway of coagulation. We then analyzed TF expression on platelets. Our results showed a higher percentage of patient’s activated platelets with surface expression of TF. In addition, to investigate the platelet hyperresponsiveness, platelets were stimulated with optimal (0,5 U/mL) and suboptimal (0,05 U/mL) concentrations of thrombin and analyzed with the same activation markers by flow cytometry. Our results showed that platelets from obese patients are hyperresponsive to suboptimal thrombin dose compared to controls. These data show that obesity patients present increased platelet activation and hyperresponsiveness.