Antithrombotic effect of FXI ASO treatment in mouse models of FeCl3-induced mesenteric vein thrombosis and stenosis-induced IVC thrombosis. Thrombus formation in male BALB/c mice treated with FXI ASO or control ASO (50 mg/kg, subcutaneously) twice weekly for 3 weeks or without treatment (“Untreated”). For testing in the mesenteric vein model, thrombosis was induced by a 3-minute exposure of the mesenteric vein to a 10% FeCl3 solution after intravenous injection of fluorescein-labeled mouse platelets. (A) Continuous recording of venous thrombus formation by intravital microscopy for a total period of 40 minutes or until total occlusion (supplemental Video 1). (B) Time to formation of a 30-μm thrombus or to total occlusion. *P ≤ .05 for FXI ASO-treated group compared with control group. For testing in the stenosis IVC model, 30 male BALB/c mice were treated with FXI ASO (dose ranging from 1.25 mg/kg to 40 mg/kg), control ASO (40 mg/kg), or saline by a twice-weekly subcutaneous injection for a period of 3 weeks. Vena cava thrombosis was induced using a model that combines reduced blood flow with endothelial damage. Twenty-four hours after thrombosis induction, thrombi that had formed in the IVC were collected, fixed in formalin, photographed, and weighed. Thrombus weight relative to saline control mice was calculated. Liver total mRNA was prepared and analyzed for FXI mRNA levels by RT-PCR. (C) The appearance of formed thrombi in the vena cava in different treatment and dosing groups. Thrombus formation in the first mouse of the FXI ASO 40-mg/kg treatment group was completely prevented. (D) Correlation of hepatic FXI mRNA levels and relative thrombus weight in mice treated with FXI ASO at indicated doses.
