NF-κB is a key mediator of cerebral aneurysm formation
NF-κB is a key mediator of cerebral aneurysm formation
复制标题
DOI：
10.1161/circulationaha.107.728303
复制
发表时间：
2007-12-11
期刊：
影响因子：
37.8
通讯作者：
Hashimoto, Nobuo
中科院分区：
文献类型：
--
作者：
Aoki, Tomohiro;Kataoka, Hiroharu;Hashimoto, Nobuo
背景-尽管最近诊断和治疗取得了进步，但脑动脉瘤（CA）破裂引起的蛛网膜下腔出血仍然是一种危及生命的疾病。近年来的研究表明，巨噬细胞介导的慢性炎症反应在CA的发病机制中起着积极的作用。我们研究了核因子-κ B（NF-κ B）在CA形成的发病机制中的作用在本study.Methods和Results-In实验诱导CA大鼠，NF-κ B被激活在脑动脉壁的动脉瘤形成的早期阶段与下游基因的表达上调。NF-κ B p50亚基缺陷小鼠显示CA形成的发生率降低，巨噬细胞浸润到动脉壁中的程度减少。NF-κ B诱饵寡核苷酸在大鼠动脉瘤形成早期给药时也可防止CA形成。NF-κ B诱骗寡核苷酸显著抑制巨噬细胞浸润和下游基因表达。在人类CA壁，NF-κ B B也被激活，特别是在intima.Conclusions-Our数据表明，NF-κ B B起着至关重要的作用，作为一个关键的调节器在启动CA的发展，通过诱导一些炎症基因相关的巨噬细胞的招聘和激活。NF-κ B B可能代表CA新的药物治疗的治疗靶点。
Background-Subarachnoid hemorrhage caused by the rupture of cerebral aneurysm (CA) remains a life- threatening disease despite recent diagnostic and therapeutic advancements. Recent studies strongly suggest the active participation of macrophage-mediated chronic inflammatory response in the pathogenesis of CA. We examined the role of nuclear factor-kappa B (NF-kappa B) in the pathogenesis of CA formation in this study.Methods and Results-In experimentally induced CAs in rats, NF-kappa B was activated in cerebral arterial walls in the early stage of aneurysm formation with upregulated expression of downstream genes. NF-kappa B p50 subunit deficient mice showed a decreased incidence of CA formation with less macrophage infiltration into the arterial wall. NF-kappa B decoy oligodeoxynucleotide also prevented CA formation when it was administered at the early stage of aneurysm formation in rats. Macrophage infiltration and expression of downstream genes were dramatically inhibited by NF-kappa B decoy oligodeoxynucleotide. In human CA walls, NF-kappa B also was activated, especially in the intima.Conclusions-Our data indicate that NF-kappa B plays a crucial role as a key regulator in the initiation of CA development by inducing some inflammatory genes related to macrophage recruitment and activation. NF-kappa B may represent a therapeutic target of a novel medical treatment for CA.