Neointimal formation is reduced after arterial injury in human crp transgenic mice
Neointimal formation is reduced after arterial injury in human crp transgenic mice
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DOI：
10.1016/j.atherosclerosis.2008.01.013
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发表时间：
2008-11-01
期刊：
影响因子：
5.3
通讯作者：
Edelman, Elazer R.
中科院分区：
文献类型：
--
作者：
Danenberg, Haim D.;Grad, Etty;Edelman, Elazer R.
目的/方法：CRP水平升高预示着心血管事件发生率的增加和干预后不良结局的发生。有研究表明，CRP也是血管损伤的中介物。携带人C反应蛋白基因(CRPtg)的转基因小鼠在损伤后易发生动脉血栓形成。我们检测了当血栓形成在通过股动脉线损伤时每天使用阿司匹林和肝素控制时，CRP是否类似地调节CRPtg中血管修复的增殖期和增生期。结果：28天时完全血栓形成动脉闭塞在野生型和CRPtg小鼠中是相似的(分别为14%和19%)。28d时CRPtg组新生内膜面积(4190+/-3134mum(2)，n=12)是野生型(10,157+/-8890mum(2，n=11，p<；0.05)的2.5倍。同样，新生内膜/中膜面积比野生型为1.10+/-0.87，CRPtg为0.45+/-0.24(p<；0.05)。损伤后7天，CRPtg组内膜细胞增殖和凋亡细胞数均低于野生型。白细胞浸润率和内皮覆盖率差异无统计学意义。结论：阿司匹林/肝素可抑制CRPtg小鼠血栓形成表型，揭示CRP对股动脉穿线损伤后新生内膜生长的影响。CRPtg组血管损伤后信号通路激活、细胞增殖和新生内膜形成均减少。我们越来越意识到C反应蛋白的多能性作用。曾经被认为只是一个危险因素，最近被认为是有害的因素，CRI？是一种复杂得多的血管生物学调节器。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Objectives/Methods: Elevated CRP levels predict increased incidence of cardiovascular events and poor outcomes following interventions. There is the suggestion that CRP is also a mediator of vascular injury. Transgenic mice carrying the human CRP gene (CRPtg) are predisposed to arterial thrombosis post-injury. We examined whether CRP similarly modulates the proliferative and hyperplastic phases of vascular repair in CRPtg when thrombosis is controlled with daily aspirin and heparin at the time of trans-femoral arterial wire-injury.Results: Complete thrombotic arterial occlusion at 28 days was comparable for wild-type and CRPtg mice (14 and 19%, respectively). Neointimal area at 28d was 2.5 fold lower in CRPtg (4190 +/- 3134 mu m(2), n = 12) compared to wild-types (10,157 +/- 8890 mu m(2), n = 11, p < 0.05). Likewise, neointimal/media area ratio was 1.10 +/- 0.87 in wild-types and 0.45 +/- 0.24 in CRPtg (p < 0.05). Seven days post-injury, cellular proliferation and apoptotic cell number in the intima were both less pronounced in CRPtg than wild-type. No differences were seen ill leukocyte infiltration or endothelial coverage. CRPtg mice had significantly reduced p38 MAPK signaling pathway activation following in C jury.Conclusions: The pro-thrombotic phenotype of CRPtg mice was suppressed by aspirin/heparin, revealing CRP's influence on neointimal growth after trans-femoral arterial wire-injury. Signaling pathway activation, cellular proliferation, and neointimal formation were all reduced in CRPtg following vascular injury. Increasingly we are aware of CRP multipotent effects. Once considered only a risk factor, and recently a harmful agent, CRI? is a far more complex regulator of vascular biology. (C) 2008 Elsevier Ireland Ltd. All rights reserved.