Abstract 293: Short-term Increases in Plasma C-Reactive Protein Concentration Accelerate Thrombosis
Background: Transgenic mice chronically over-expressing human C-reactive protein (CRP) demonstrate increased thrombosis. However, it is unknown whether short-term increases in plasma CRP, as are observed in acute inflammatory disorders, alter the thrombotic respons to vascular injury. We tested the hypothesis that short-term up-regulation of CRP accelerates thrombosis.
Methods: Highly purified human CRP (free of detectable endotoxin and extensively dialyzed to remove sodium azide) or vehicle control were administered to male C57BL/6J mice by intraperitoneal injection 16 and 2 hours before surgically exposing the carotid artery and inducing photochemical injury (Rose Bengal/green light model). Time required to form a completely occlusive thrombus was measured and blood coagulation parameters were studied.
Results: Mean occlusion time (OT) was 12.9±1.1 min in mice administered CRP 6 mg/kg/injection vs. 18.5±2.3 min in mice administered vehicle (16 mice/group; P<0.02). However, mean OT of mice administered CRP 1 mg/kg/injection (20.0±2.0 min, n=16) did not differ significantly from vehicle-treated mice. Mean serum CRP concentrations were 18.8±3.1, 4.6±0.6, and 0.04±0.02 μg/mL in mice treated with CRP 6, 1, and 0 mg/kg/injection, respectively. Administration of CRP did not increase plasma thrombin-antithrombin complex concentration, alter prothrombin or activated partial thromboplastin times, or increase tissue factor activity in plasma, liver, or the carotid arterial wall as compared to vehicle control.
Conclusion: Short-term increases in plasma CRP concentration accelerate the thrombotic response of arterial injury, but there is a threshold effect with high plasma CRP concentration appearing necessary to enhance thrombosis. Since plasma CRP concentration can increase markedly during acute illness, our data suggest that CRP may mediate the increased risk of thrombosis observed during acute inflammation. Further studies are necessary to determine the mechanisms by which CRP accelerates thrombosis.