Fenofibrate Inhibits Tissue Factor Expression And Preliminary Appliance Of Whole Blood TiFaCT Assay In Monitoring Thrombogenicity

Objective: To construct a cell model which tissue factor(TF) mRNA is induced expression in monocytes, and investigate the effects of fenofibrate on the TF expression and TF procoagulant activity (PCA) induced by lipopolysaccharide (LPS). Meanwhile, to preliminarily evaluate whole blood Tissue Factor Clotting Time( TiFaCT ) assay on monitoring thrombogenicity risk in patients of thrombotic disease.Methods: Constructed a cell model of TF mRNA was induced expression in monocytes with different LPS concentration or different incubated time. Pretreated monocytes with fenofibrate of different concentration, and studied the effects of fenofibrate on LPS-induced TFmRNA,TF protein levels and TF-PCA which were measured by RT-PCR,flow cytometry and TiFaCT respectively. We measured whole blood basal and LPS-induced TF-PCA with whole blood TiFaCT assay in patients with thrombotic disease and normal controls.Results: 1 We Constructed a cell model of TF mRNA was induced expression in monocytes with 10μg/ml LPS incubated for 3h. Compared to the LPS-stimulated THP-1 cells, fenofibrate inhibited LPS-induced TFmRNA,TF protein expression and TF-PCA to 66%,47% and 29%,respectively (P<0.05). 50μmol/L fenofibrate didn't affect basal TF-PCA but inhibited LPS-induced TF-PCA obviously.2 We measured TF-PCA with whole blood TiFaCT assay and found patients with thrombotic disease had a higher basal TF-PCA and LPS-induced TF-PCA , which were (1.33±0.53)AU and (9.42±4.79)AU, compared with normal controls that was(0.31±0.29)AU and (1.59±1.26) AU, respectively. The LPS-induced whole blood TF-PCA in patients of thrombotic disease with disseminated intravascular coagulation (DIC) was higher than that in the non-DIC group.Conclusions: 1 We had constructed a cell model of tissue factor mRNA which was induced expression in monocytes.2 The data indicated that fenofibrate inhibited LPS-induced TF expression and TF-PCA, but did not affect basal TF-PCA. The results suggest that fenofibrate have an application prospect of anti-thrombosis.3 The patients with thrombotic disease had a higher baseline TF-PCA and LPS-induced TF-PCA, compared with normal controls. The LPS induced whole blood TF-PCA in patients sufferring from thrombotic disease with DIC group was higher than non-DIC group. These results showed that the whole blood TiFaCT assay should have a potential role in evaluating the risks of thrombogenicity in patients with thrombotic disease.