Abstract 15833: C-Reactive Protein Increases Tissue Factor Expression and Promotes Thrombosis in Vein Bypass Grafts
Background: Increased expression of C-reactive protein (CRP) is associated with early occlusion of vein bypass grafts (VGs), a major clinical problem in which thrombosis plays a key role. In vitro studies have shown that CRP promotes expression of prothrombotic factors, including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1). However, little is known about the effect of CRP on TF and PAI-1 expression in VGs and post-operative VG thrombosis.
Methods and Results: We studied male transgenic (Tg) mice expressing human CRP under the control of its native promoter. Segments of inferior vena cava from wild-type (WT) and CRP-Tg donors were surgically implanted into transected carotid arteries of WT and CRP-Tg recipients. One week after surgery VGs were harvested and gene expression in them was studied using real-time reverse transcriptase (RT)-PCR. There was no significant difference in VG PAI-1 gene expression between CRP-Tgdonor/CRP-Tgrecipient and WTdonor/WTrecipient mice (n=6/group, P>0.05), whereas VG TF gene expression was 2.4±0.4-fold higher in the former group (P<0.05). Plasma PAI-1 concentration did not differ between groups, whereas plasma CRP was significantly higher in CRP-Tg mice than WT controls. RT-PCR analysis of VGs and livers of CRP-Tgdonor/WTrecipient and CRP-Tgdonor/CRP-Tgrecipient mice revealed that CRP gene expression was robust in liver, but essentially undetectable in VGs. To study the effect of CRP on fibrin formation in VGs we performed surgery in a second series of mice. After 7 days VGs were exposed and subjected to endothelium-denuding mechanical injury. After 60 min (during which time mural fibrin deposition occurred, though lumens did not completely occlude) VGs were excised, rinsed, and pulverized. Extracts were prepared and subjected to quantitative Western blot analysis with a fibrin-specific antibody. VG fibrin formation was 1.8±0.1-fold higher in CRP-Tgdonor/CRP-Tgrecipient vs. WTdonor/WTrecipient mice (n=6/group; P<0.05).
Conclusions: CRP increases TF gene expression in VGs and promotes thrombosis in the early post-surgical period. Our results suggest that increased systemic CRP expression induces pathological changes in VGs that promote thrombosis and contribute to early VG occlusion.
- © 2013 by American Heart Association, Inc.