Session: 321. Blood Coagulation and Fibrinolytic Factors: Coagulation and Fibrinolytic Factors: Regulation of Coagulation
Hematology Disease Topics & Pathways:
Biological Processes, molecular interactions
Approach and Results: We found that cellular Fn-EDA levels were significantly elevated in plasma of venous thromboembolism (VTE) patients that positively correlated with body mass index (BMI). To investigate whether Fn-EDA promotes venous thrombosis in obese condition, WT and Fn-EDA-/- mice were either fed a control or high-fat diet (HF-diet) for 12-weeks. DVT was induced by inferior vena cava stenosis and evaluated after 48 hours. We found that HF diet-fed WT mice exhibited increased DVT susceptibility compared with control diet-fed WT mice. In contrast, HF-fed Fn-EDA-/- mice exhibited significantly reduced thrombus weight and decreased incidence (%) of DVT compared with HF-fed WT mice that was concomitant with improved blood flow, reduced neutrophil content and citrullinated histone H3-positive cells (a marker of NETosis) in IVC thrombus. Exogenous Fn-EDA potentiated NETosis in neutrophils stimulated with thrombin-activated platelets via TLR4. Genetic deletion of TLR4 in Fn-EDAfl/fl mice, which constitutively express Fn-EDA, reduced DVT compared with Fn-EDAfl/fl mice.
Conclusion: These results demonstrate a previously unknown role of Fn-EDA in the modulation of DVT, which may be an important mechanism promoting DVT in the setting of obesity.
Disclosures: No relevant conflicts of interest to declare.
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