Ruusalepp Arno, Yan Zhong-Qun, Carlsen Harald, Czibik Gabor, Hansson Göran K, Moskaug Jan-Øyvind, Blomhoff Rune, Valen Guro
Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Norway.
Cardiovasc Drugs Ther. 2006 Apr;20(2):103-11. doi: 10.1007/s10557-006-6755-7.
The role of nuclear factor kappa-B (NF-kappaB) p105 for vascular inflammatory gene expression and neointima formation after arterial injury was studied. Mice carotid arteries were injured by ligation. Vascular NF-kappaB activation was monitored using a NF-kappaB luciferase reporter mouse. Mice with gene deletion of the NF-kappaB p105 subunit (p50 precursor) and the corresponding wild types were assessed for vascular gene expression and neointimal hyperplasia. NF-kappaB was activated in the injured vessel wall in wild type mice, and this was accompanied by increased expression of the proinflammatory genes tumor necrosis factor alpha, interleukin 1 beta, and inducible nitric oxide synthase. In contrast, NF-kappaB p105 knockout mice had reduced expression of the inflammatory genes and enhanced neointima formation four weeks after ligation. Basic fibroblast growth factor (bFGF) gene expression increased after arterial ligation. A higher percentage of bFGF positive cells were found in lesions from NF-kappaB p105 knock out mice. These data indicate that the p105 subunit of NF-kappaB plays an essential role in vascular healing, and defects in NF-kappaB p105 promote neointima hyperplasia.
研究了核因子κB（NF-κB）p105在动脉损伤后血管炎症基因表达和新生内膜形成中的作用。通过结扎损伤小鼠颈动脉。使用NF-κB荧光素酶报告基因小鼠监测血管NF-κB激活。评估NF-κB p105亚基（p50前体）基因缺失的小鼠和相应野生型小鼠的血管基因表达和内膜增生情况。野生型小鼠损伤血管壁中的NF-κB被激活，同时促炎基因肿瘤坏死因子α、白细胞介素1β和诱导型一氧化氮合酶的表达增加。相比之下，NF-κB p105基因敲除小鼠在结扎四周后炎症基因表达降低，新生内膜形成增强。动脉结扎后碱性成纤维细胞生长因子（bFGF）基因表达增加。在NF-κB p105基因敲除小鼠的病变中发现更高比例的bFGF阳性细胞。这些数据表明，NF-κB的p105亚基在血管愈合中起重要作用，NF-κB p105缺陷促进新生内膜增生。
