Human C-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits
Human C-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits
复制标题
DOI：
10.1111/j.1538-7836.2010.04086.x
复制
发表时间：
2011-01-01
影响因子：
10.4
通讯作者：
Asada, Y.
中科院分区：
文献类型：
--
作者：
Matsuda, S.;Yamashita, A.;Asada, Y.
背景：高水平的C-反应蛋白(CRP)是心血管事件的有力预测标记物。多项证据表明，C反应蛋白具有促血栓形成作用。然而，C反应蛋白是否直接参与体内血栓形成的发病机制尚未完全阐明。目的：探讨人C反应蛋白(HCRP)对富含平滑肌细胞(SMC)和富含巨噬细胞的新生内膜球囊损伤后血栓形成的影响。方法：比较表达hCRP的转基因兔(46.21+/-13.85 mg L-1，n=22)和非转基因兔对富含SMC或巨噬细胞的新生内膜球囊损伤后血栓形成的易感性。结果：与非TG兔相比，hCRP-TG兔富含SMC或巨噬细胞的新生内膜血栓明显增大，并伴有纤维蛋白含量增加。在hCRP-TG兔富含SMC和富巨噬细胞的新生内膜中，血栓大小没有显著差异。HCRP-TG组与非TG组相比，组织因子(TF)mRNA表达和活性显著增加。C反应蛋白沉积程度与损伤新生内膜组织因子表达升高及血栓大小相关。此外，从hCRP-TG兔血浆中提取的hCRP还可诱导培养的兔血管平滑肌细胞表达Tf基因并激活其活性。结论：血浆hCRP水平升高可能通过促进Tf表达促进富含SMC的损伤新生内膜血栓的形成，但对富含巨噬细胞的新生内膜无相加作用。
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.