Human C‐reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits

Background: High plasma levels of C‐reactive protein (CRP) constitute a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP has prothrombogenic effects. However, whether CRP directly participates in the pathogenesis of thrombosis in vivo has not been fully clarified. Objective: To test whether human CRP (hCRP) affects arterial thrombus formation after balloon injury of smooth muscle cell (SMC)‐rich or macrophage‐rich neointima. Methods: We compared the susceptibility of transgenic (Tg) rabbits expressing hCRP (46.21 ± 13.85 mg L−1, n = 22) and non‐Tg rabbits to arterial thrombus formation after balloon injury of SMC‐rich or macrophage‐rich neointima. Results: Thrombus size on SMC‐rich or macrophage‐rich neointima was significantly increased, and was accompanied by an increase in fibrin content in hCRP‐Tg rabbits, as compared with non‐Tg rabbits. Thrombus size did not significantly differ between SMC‐rich and macrophage‐rich neointima in hCRP‐Tg rabbits. Tissue factor (TF) mRNA expression and activity in these neointimal lesions were significantly increased in hCRP‐Tg rabbits as compared with non‐Tg rabbits. The degree of CRP deposition correlated with the elevated TF expression and thrombus size on injured neointima. In addition, hCRP isolated from hCRP‐Tg rabbit plasma induced TF mRNA expression and activity in rabbit cultured vascular SMCs. Conclusions: These results suggest that elevated plasma hCRP levels promote thrombus formation on injured SMC‐rich neointima by enhancing TF expression, but have no additive effects in macrophage‐rich neointima.