Investigação da ativação plaquetária em pacientes com obesidade

Abstract

Obesity is a condition characterized by chronic low-grade inflammation associated with metabolic alterations. Studies have demonstrated that individuals with obesity exhibit a prothrombotic state characterized by platelet activation and hyperresponsiveness, contributing to an increased propensity for thrombus formation and a higher cardiometabolic risk. However, the mechanisms underlying these processes remain incompletely understood. Therefore, we hypothesized that platelet activation contributes to thromboinflammation in obesity. Blood samples from individuals with obesity and eutrophic controls were collected for platelet isolation and the assessment of platelet activation, as well as the plasma levels of the platelet-derived mediators sCD62P and PF4/CXCL4. Platelet activation was evaluated by flow cytometry using the markers CD62P, CD63, PAC-1, and tissue factor (TF), while the levels of RANTES/CCL5, sCD62P, platelet-derived growth factor (PDGF), and PF4/CXCL4 were quantified in the supernatants of thrombin-stimulated platelets by ELISA. The results showed higher plasma concentrations of CXCL4/ PF4 in individuals with obesity, accompanied by an increased percentage of activated platelets expressing CD63, CD62P (P-selectin), and PAC-1 compared with eutrophic controls, indicating enhanced platelet activation. To investigate platelet hyperresponsiveness, platelets were stimulated with optimal (0.5 U/mL) and suboptimal (0.05 U/mL) concentrations of thrombin and analyzed using the same markers. Platelets from individuals with obesity exhibited increased CD63 expression following stimulation, demonstrating a hyperresponsive phenotype. In contrast, we observed reduced sCD62P secretion by platelets from individuals with obesity following stimulation with the optimal thrombin concentration. When flow cytometry data were stratified according to obesity severity, individuals with class II–III obesity also exhibited lower CD62P expression under the same stimulation conditions, suggesting possible depletion of platelet P-selectin granule stores in obesity. Under basal conditions, individuals with class II–III obesity displayed higher CD62P expression and increased PAC-1 expression following stimulation with the suboptimal thrombin concentration. Collectively, these findings demonstrate increased platelet activation and hyperresponsiveness in obesity, particularly in class II–III obesity, and suggest that chronic platelet activation leads to depletion of platelet P-selectin granule content.