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KMID : 0928520070170010011
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Korean Journal of Lipidology
2007 Volume.17 No. 1 p.11 ~ p.18
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PPARγActivation Abolishes LDL-induced Proliferation of Human Aortic Smooth Muscle Cells via Erk1/2-mediated Down-regulation of Egr-1
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Heo Kyung-Sun
Kim Dong-Uk
Nam Mi-Young
Baek Seung-Tae
Lee Hye-Mi
Hwang Hye-Rim
Park Song-Kyu
Park Young-Woo
Lee Sung-Hou
Myung Chang-Seon
Hoe Kwang-Lae
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Abstract
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Objective: Native LDL would be a mitogenic and chemotactic stimulus of VSMC proliferation in the atherosclerotic lesion where endothelial disruption occurred. Among peroxisome proliferative-activated receptors (PPARs) α, γ, and β/δ, as transcription factors exerting modulatory action in vascular cells, PPARγ exhibits antiatherogenic properties and its agonists are applied to patients in cardiovascular disease. The aim of the study was to investigate the effects of PPARγ agonist troglitazone (TG) on LDL-induced cell proliferation in human aortic smooth muscle cells (hAoSMCs).
Methods: Human AoSMCs were treated with LDL in dose- and time-dependent manners. Cell proliferation was determined by WST-1 and BrdU incorporation assays. The activity of extracellular signal-regulated kinase1/2 (Erk1/2) and early growth response factor 1 (Egr-1) was measured by Western blot using phospho-Erk and Egr-1 antibodies. Specific inhibition of TG on Egr-1 transcriptional expression was determined by Northern blot analysis.
Results: Treatment of hAoSMCs with LDL increased cell proliferation in dose- and time-dependent manners. LDL-induced cell proliferation was accompanied by Erk1/2 activation and sequential up-regulation of Egr-1. PPARγ activation by TG exerted its inhibitory effects on LDL-induced cell proliferation via Erk1/2-dependent down-regulation of Egr-1 in hAoSMCs.
Conclusion: PPARγ activation exerts its beneficial effects on LDL-induced cell proliferation of hAoSMCs.
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KEYWORD
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Low-density lipoproteins, Egr-1, MAP kinase, PPAR, Smooth muscle cell, Troglitazone
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