Effect of cytochrome P450-dependent epoxyeicosanoids on Ristocetin-induced thrombocyte aggregation

摘要: Epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 (CYP)-dependent epoxidation of arachidonic acid (AA) inhibit thrombocyte adhesion to the vascular wall. Upon dietary omega-3 fatty supplementation, EETs are partially replaced eicosapentaenoic (EPA)-derived epoxyeicosatetraenoic (EEQs) and docosahexaenoic (DHA)-derived epoxydocosapentaenoic (EDPs). We hypothesized that epoxy-metabolites may exhibit superior anti-thrombogenic properties compared their AA-derived counterparts. To test this hypothesis, we analyzed effects 11,12-EET, 17,18-EEQ 19,20-EDP on Ristocetin-induced aggregation (RITA), a process mimics The eicosanoids were added for 5, 30, or 60 minutes thrombocyte-rich plasma freshly prepared immediately after blood collection from stringently selected apparently healthy subjects. Thrombocyte was then induced Ristocetin (0.75 mg/mL) assessed turbidimetric measurements. After preincubation, all three significantly decreased rate RITA. effective already at 1 μM, whereas 5-fold higher concentrations required with 11,12-EET. Addition AUDA, an inhibitor soluble epoxide hydrolase, potentiated effect resulting in significant further decrease velocity as well amplitude process. In contrast profound RITA, none reducing collagen- ADP-induced aggregation. These results indicate highly specific role CYP-eicosanoids preventing thromboembolic events suggest formation contribute anti-thrombotic acids.