Effects of PGC-1α at on TNF-α-induced MCP-1 and VCAM-1 expression and NF-κB activation in human aortic smooth muscle and endothelial cells
Effects of PGC-1α at on TNF-α-induced MCP-1 and VCAM-1 expression and NF-κB activation in human aortic smooth muscle and endothelial cells
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DOI：
10.1089/ars.2006.1456
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发表时间：
2007-03-01
影响因子：
6.6
通讯作者：
Lee, In-Kyu
中科院分区：
文献类型：
--
作者：
Kim, Hye-Jin;Park, Keun-Gyu;Lee, In-Kyu
血管细胞氧化应激增加与动脉粥样硬化的发病机制有关。活性氧（ROS）通过促炎细胞因子/ nf - κ B途径诱导血管炎症。多项证据表明，过氧化物酶体增殖体激活受体- γ辅助激活因子1- α (PGC-1 α)是细胞内ROS水平的重要调节因子。然而，没有研究检测PGC-1 α在这一过程中的作用。我们研究了PGC-1 α对血管细胞中炎症分子表达和氧化还原敏感转录因子nf - κ B活性的影响。PGC-1 α在人主动脉平滑层（HASMCs）和内皮细胞（HAECs）中的表达被amp激活的蛋白激酶激活剂上调，包括二甲双胍、罗格列酮和α -硫辛酸。肿瘤坏死因子- α (tnf - α)是血管炎症发展中的主要促炎因子，通过增加线粒体ROS和NAD(P)H氧化酶活性来刺激细胞内ROS的产生。腺病毒介导的PGC-1 α基因在HASMCs和HAECs中的过表达导致细胞内和线粒体ROS生成以及NAD(P)H氧化酶活性显著降低。因此，tnf - α诱导的NF-kappa B活性和MCP-1和VCAM-1被抑制。我们的数据支持刺激血管中PGC-1 α表达的药物有助于预防动脉粥样硬化发展的可能性。
Increased oxidative stress in vascular cells is implicated in the pathogenesis of atherosclerosis. Reactive oxygen species (ROS) induce vascular inflammation via the proinflammatory cytokine/NF-kappa B pathway. Several lines of evidence suggest that peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1 alpha) is an important regulator of intracellular ROS levels. However, no studies have examined the effects of PGC-1 alpha on this process. We investigated the effects of PGC-1 alpha on inflammatory molecule expression and activity of the redox-sensitive transcription factor, NF-kappa B, in vascular cells. PGC-1 alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid. Tumor necrosis factor-alpha (TNF-alpha), a major proinflammatory factor in the development of vascular inflammation, stimulates intracellular ROS production through an increase in both mitochondrial ROS and NAD(P)H oxidase activity. Adenovirus-mediated overexpression of the PGC-1 alpha gene in HASMCs and HAECs leads to a significant reduction in intracellular and mitochondrial ROS production as well as NAD(P)H oxidase activity. Consequently, NF-kappa B activity and MCP-1 and VCAM-1 induced by TNF-alpha are suppressed. Our data support the possibility that agents stimulating PGC-1 alpha expression in the vasculature aid in preventing the development of atherosclerosis.