Orphan nuclear receptor small heterodimer partner inhibits
angiotensin II-stimulated PAI-1 expression in vascular smooth
muscle cells
- Affiliated Author(s)
- 김미경; 류성열; 김윤년; 박근규
- Alternative Author(s)
- Kim, Mi Kyung; Ryu, Seong Yeol; Kim, Yoon Nyun; Park, Keun Gyu
- Journal Title
- Experimental and Molecular Medicine.
- ISSN
- 1226-3613
- Issued Date
- 2010
- Abstract
- 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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