PPARγ activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via Erk1/2-mediated down-regulation of Egr-1

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Title
PPARγ activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via Erk1/2-mediated down-regulation of Egr-1
Author(s)
Kyung Sun Heo; Dong Uk Kim; Miyoung Nam; Seung-Tae Baek; Hye Mi Lee; Hye Rim Hwang; Song Kyu Park; Young Woo Park; S Lee; C S Myung; Kwang Lae Hoe
Bibliographic Citation
Korean Journal of Lipidology, vol. 17, no. 1, pp. 11-18
Publication Year
2007
Abstract
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) , γ, and / , 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.
Keyword
Low-density lipoproteinsEgr-1MAP kinasePPARSmooth muscle cellTroglitazone
ISSN
I000-0017
Publisher
Korea Soc-Assoc-Inst
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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