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

Cited 5 time in Web of Science Cited 5 time in Scopus
Authors
Lee, Kyeong-Min; Seo, Hye-Young; Kim, Mi-Kyung; Min, Ae-Kyung; Kim, Yoon-Nyun; Choi, Hueng-Sik; Park, Wan-Ju; Lee, In-Kyu; Park, Keun-Gyu; Lee, Ki-Up; Park, Young Joo; Ryu, Seong-Yeol
Issue Date
2010-01-31
Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE; Vol.42 1; 21-29
Keywords
angiotensin IImuscle, smooth, vascularatherosclerosisnuclear receptor subfamily 0, group B, member 2transforming growth factor betaplasminogen activator inhibitor 1
Abstract
Angiotensin 11 is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin 11 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-beta 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-beta-stimulated PAI-1 expression. Ad-SHP also inhibited angiotensin II-, TGF-beta- 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 11 treatment. These results suggest that SHP inhibits PAI-1 expression in VSMCs through the suppression of TGF-beta/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.
ISSN
1226-3613
Language
English
URI
http://hdl.handle.net/10371/76567
DOI
https://doi.org/10.3858/emm.2010.42.1.002
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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