Figure 5
Figure 5. Antithrombotic effect of PKK and fXII ASO treatments in mouse model of FeCl3-induced mesenteric artery thrombosis. Male Swiss Webster mice were treated with either PKK (A) or fXII (B) ASO at indicated doses administered subcutaneously for 3 weeks (n = 6-8 per treatment group). Mesenteric artery thrombosis was induced by a 3 minute exposure of the mesenteric vein to a 6% FeCl3 solution. Platelets were labeled through subcutaneous injection of Rhodamine-6G and fibrin was labeled through intravenous injection of Alexa 647–conjugated anti-fibrinogen antibody. Continuous recording of venous thrombus formation by confocal intravital microscopy (confocal-IVM) was done for a total period of 70 minutes. Normalized integral intensity for each of 2 channels (fibrin and platelet detection) was plotted against time. Intensities for control group are shown in black, 10 mg/kg/wk dose of PKK and fXII ASOs are shown in blue, 20 mg/kg/wk dose in green, 40 mg/kg/wk dose in yellow, and 80 mg/kg/wk dose in red. Platelet and fibrin content of formed thrombi in the vena cava in different treatment groups at different time points is shown in panel C. Comparison of effects of PKK and fXII protein inhibition in FeCl3-induced platelet aggregation (D) and fibrin accumulation (E) in mesenteric artery. *P ≤ .05, **P ≤ .01 and ***P ≤ .001 compared with untreated control.

Antithrombotic effect of PKK and fXII ASO treatments in mouse model of FeCl3-induced mesenteric artery thrombosis. Male Swiss Webster mice were treated with either PKK (A) or fXII (B) ASO at indicated doses administered subcutaneously for 3 weeks (n = 6-8 per treatment group). Mesenteric artery thrombosis was induced by a 3 minute exposure of the mesenteric vein to a 6% FeCl3 solution. Platelets were labeled through subcutaneous injection of Rhodamine-6G and fibrin was labeled through intravenous injection of Alexa 647–conjugated anti-fibrinogen antibody. Continuous recording of venous thrombus formation by confocal intravital microscopy (confocal-IVM) was done for a total period of 70 minutes. Normalized integral intensity for each of 2 channels (fibrin and platelet detection) was plotted against time. Intensities for control group are shown in black, 10 mg/kg/wk dose of PKK and fXII ASOs are shown in blue, 20 mg/kg/wk dose in green, 40 mg/kg/wk dose in yellow, and 80 mg/kg/wk dose in red. Platelet and fibrin content of formed thrombi in the vena cava in different treatment groups at different time points is shown in panel C. Comparison of effects of PKK and fXII protein inhibition in FeCl3-induced platelet aggregation (D) and fibrin accumulation (E) in mesenteric artery. *P ≤ .05, **P ≤ .01 and ***P ≤ .001 compared with untreated control.

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