Effect of PGC-1α on TNF-α-Induced MCP-1 and VCAM-1 Expression and NF-κB Activation in Human Aortic Smooth Muscle and Endothelial Cells
- Affiliated Author(s)
- 김윤년; 김혜순; 이인규
- Alternative Author(s)
- Kim, Yoon Nyun; Kim, Hye Soon; Lee, In Kyu
- Journal Title
- Antioxidants & Redox Signaling
- Issued Date
- 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-κB pathway. Several lines of evidence suggest that peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) is an important regulator of intracellular ROS levels. However, no studies have examined the effects of PGC-1α on this process. We investigated the effects of PGC-1α on inflammatory molecule expression and activity of the redox-sensitive transcription factor, NF-κB, in vascular cells. PGC-1α expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and α-lipoic acid. Tumor necrosis factor-α (TNF-α), 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-1α 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-κB activity and MCP-1 and VCAM- 1 induced by TNF-α are suppressed. Our data support the possibility that agents stimulating PGC-1α expression in the vasculature aid in preventing the development of atherosclerosis.
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