Coagulation Factor Xa Stimulates Interleukin-8 Release in Endothelial Cells and Mononuclear Leukocytes

Objective— In acute myocardial infarction (AMI), proinflammatory plasma C-reactive protein values are strongly associated with postinfarction morbidity and mortality. So far, the cause of these inflammatory changes is not well understood. Therefore, we sought to investigate the relationship between the activation of coagulation and subsequent systemic inflammatory changes in AMI. Methods and Results— Factor Xa (FXa) bound to tissue factor pathway inhibitor and prothrombin fragments F1+2 (F1+2) were used as a measure for activated coagulation. To assess systemic inflammatory changes, plasma interleukin (IL)-6 and IL-8 concentrations were analyzed by immunoassay. Blood samples were taken from 21 patients with AMI and 20 patients with stable angina pectoris. In AMI, tissue factor pathway inhibitor FXa but not F1+2 plasma levels were associated with circulating IL-8 (P=0.01). In vitro experiments revealed that FXa stimulated IL-8 and monocyte chemoattractant protein-1 release and RNA expression in endothelial...