Inflammatory signaling pathway containing TRAF6 contributes to neointimal formation via diverse mechanisms.
Inflammatory signaling pathway containing TRAF6 contributes to neointimal formation via diverse mechanisms.
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DOI：
10.1016/j.cardiores.2004.06.014
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发表时间：
2004-10
影响因子：
10.8
通讯作者：
T. Miyahara;H. Koyama;T. Miyata;H. Shigematsu;J. Inoue;T. Takato;H. Nagawa
中科院分区：
文献类型：
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作者：
T. Miyahara;H. Koyama;T. Miyata;H. Shigematsu;J. Inoue;T. Takato;H. Nagawa
目的：探讨含肿瘤坏死因子受体相关因子6(TRAF6)的炎症信号在兔颈动脉球囊损伤模型中对新生内膜形成的影响。通过体内电穿孔的方法将TRAF6的显性负性(DN)形式转移到兔颈总动脉球囊损伤模型上，观察其对球囊损伤后血管内膜损伤形成的影响。结果：成功地将含有TRAF6 DNA序列的表达载体转入动脉壁细胞，并在损伤后显著抑制核因子-κB(NF-κB)活性，证实了其对炎症信号的抑制作用。形态计量学分析显示，损伤后7天内膜病变的形成受到明显抑制。伤后2天，巨噬细胞在中膜的复制和积聚明显减少，细胞凋亡率增加。伤后4天，细胞向内膜迁移受到抑制。细胞外信号调节蛋白1/2(ERK1/2)活性在伤后2小时表达下调。结论：TRAF6除促进炎症细胞浸润和抑制细胞凋亡外，还参与细胞的复制和迁移。
Objective:The purpose of this study was to investigate the contribution of inflammatory signaling containing tumor necrosis factor receptor-associated factor 6 (TRAF6) to neointimal formation in a balloon injury model of rabbit carotid artery.Methods:Male Japanese white rabbits fed a normal diet were used. We transferred the dominant negative (DN) form of TRAF6 to a rabbit carotid artery that was subjected to balloon injury by in vivo electroporation method, and then evaluated its effect on intimal lesion formation after balloon injury.Results:An expression plasmid vector containing the TRAF6 DN sequence was successfully transferred to arterial wall cells, and its inhibitory effect on inflammatory signaling was confirmed by the marked suppression of nuclear factor-κB (NFκB) activity after injury. Morphometric analyses revealed significant inhibition of intimal lesion formation at 7 days after injury. Cell replication and accumulation of macrophages in the media were significantly decreased, and apoptosis was enhanced on day 2. Cell migration to the intima was suppressed on day 4. Extracellular signal-regulated kinase1/2 (ERK1/2) activity at 2 h after injury was also down-regulated. Interestingly, intimal cell replication was significantly blocked when TRAF6 DN was transfected at 7 days after injury.Conclusion:TRAF6 plays important roles in cell replication and migration, besides promotion of inflammatory cell infiltration and suppression of apoptosis.