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Signal transduction regulating intimal cell replication in arterial lesion

信号转导调节动脉病变内膜细胞复制

基本信息

批准号：
12470236
负责人：
KOYAMA Hiroyuki
金额：
$ 6.66万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470236/
关键词：
stent reinjury rabbit TRAF inflammation intimal hyperplasia smooth muscle cell Phosphatidylinositol-3-kinase Pootion kinase C p70^<S6k>血管内ステントラビット再障害モデル Protein kinase B Protein kinase C

项目摘要

1. In order to study the mechanisms of neointimal cell replication, we developed an experimental model of stent implantation to preexisting intimal hyperplasia, which utilized rabbit carotid artery. Briefly, the carotid artery was subjected to ordinary balloon injury with 2F Fogarty catheter, and 28 days later, 3-mm diameter Palmaz stent was implanted in the same carotid artery. Since neointimal hyperplasia had been developed by 28 days after the balloon injury, stent was implanted into the developed intimal lesion, which mimicked clinical setting. The stent implantation promoted intimal cell replication and in-stent lesion formation. Macrophage infiltration around stent strut and leukocyte adhesion to luminal surface were also observed after stent implantation, suggesting that inflammatory reactions played an important role in in-stent lesion formation.2. To investigate how inflammatory reactions in the arterial wall influences intimal lesion formation, we transferred dominant negative (DN) of TRAF-6, potent key component of inflammatory signaling, into the arterial wall by in vivo electroporation method. TRAF-6 DN significantly inhibited medial and intimal cell replication, which was associated with the suppressed activity of ERK1/2 and NF-kB. Further, TRAF-6 DN increased apoptos is in the medial layer, and significantly blocked cell migration from media to intima. These findings indicated that inhibition of inflammatory signaling suppressed intimal lesion formation in the arterial wall.

1.为了研究新生内膜细胞复制的机制，我们建立了兔颈总动脉支架植入的实验模型。简言之，颈动脉用2F Fogarty导管进行普通球囊损伤，28天后，在同一颈动脉中植入直径为3 mm的Palmaz支架。由于球囊损伤后28天已发生新生内膜增生，因此将支架植入到发生的内膜病变中，模拟临床环境。支架植入促进内膜细胞复制和支架内病变形成。支架植入后支架周围巨噬细胞浸润，白细胞粘附于管腔表面，提示炎症反应在支架内病变形成中起重要作用.为了研究动脉壁中的炎症反应如何影响内膜损伤形成，我们通过体内电穿孔方法将TRAF-6（炎症信号传导的有效关键组分）的显性阴性（DN）转移到动脉壁中。TRAF-6 DN显着抑制中膜和内膜细胞复制，这与ERK 1/2和NF-kB活性抑制有关。此外，TRAF-6 DN增加了中膜层中的内皮细胞，并显著阻断了细胞从中膜向内膜的迁移。这些发现表明，抑制炎症信号抑制动脉壁内膜损伤的形成。