Orphan nuclear receptor small heterodimer partner inhibits angiotensin II-stimulated PAI-1 expression in vascular smooth muscle cells

Kyeong-Min LeeHye-Young SeoMi-Kyung KimAe-Kyung MinSeong-Yeol RyuYoon-Nyun KimYoung Joo ParkHueng-Sik ChoiKi-Up LeeWan-Ju ParkKeun-Gyu ParkIn-Kyu Lee
Dept. of Internal Medicine (내과학); Institute for Medical Science (의과학연구소)
Issue Date
Experimental and Molecular Medicine., Vol.42(1) : 21-29, 2010
Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor- 1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of TGF-β signaling pathways. Here, we investigated whether SHP inhibited angiotensin II-stimulated PAI-1 expression in VSMCs. Adenovirus-mediated overexpression of SHP (Ad- SHP) in VSMCs inhibited angiotensin II- and TGF-β-stimulated PAI-1 expression. Ad-SHP also inhibited angiotensin II-, TGF-β- and Smad3-stimulated PAI-1 promoter activity, and angiotensin II-stimulated AP-1 activity. The level of PAI-1 expression was significantly higher in VSMCs of SHP-/- mice than wild type mice. Moreover, loss of SHP increased PAI-1 mRNA expression after angiotensin II treatment. These results suggest that SHP inhibits PAI-1 expression in VSMCs through the suppression of TGF-β/Smad3 and AP-1 activity. Thus, agents that target the induction of SHP expression in VSMCs might help prevent the development and progression of atherosclerosis. Keywords: angiotensin II; atherosclerosis; muscle, smooth, vascular; nuclear receptor subfamily 0, group B, member 2; plasminogen activator inhibitor 1; transforming growth factor β
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. Journal Papers (연구논문) > 3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
Keimyung Author(s)
김미경; 류성열; 김윤년; 박근규
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