(Circulation. 2000;102:1834.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Peroxisome Proliferator-Activated Receptor 
Activators Downregulate Angiotensin II Type 1 Receptor in Vascular Smooth Muscle Cells
From the Departments of Cardiovascular Medicine (K.T., T.I., T.T., Y.F., N.I., A.T.) and Molecular Cardiology (K.H., H.K.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Correspondence to Toshihiro Ichiki, MD, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan. E-mail ichiki{at}cardiol.med.kyushu-u.ac.jp
Background—Peroxisome
proliferator-activated receptor 
(PPAR)
activators, such as troglitazone (Tro), not only improve
insulin resistance but also suppress the neointimal
formation after balloon injury. However, the precise mechanisms have
not been determined. Angiotensin II (Ang II) plays crucial
roles in the pathogenesis of atherosclerosis,
hypertension, and neointimal formation after angioplasty.
We examined the effect of PPAR activators on the
expression of Ang II type 1 receptor (AT1-R) in cultured
vascular smooth muscle cells (VSMCs).
Methods and Results—AT1-R mRNA and AT1-R
protein levels were determined by Northern blot analysis and
radioligand binding assay, respectively. Natural PPAR
ligand 15-deoxy-
12,14-prostaglandin
J2, as well as Tro, reduced the AT1-R mRNA
expression and the AT1-R protein level. The PPAR
activators also reduced the calcium response of VSMCs to
Ang II. PPAR activators suppressed the AT1-R
promoter activity measured by luciferase assay but did not affect the
AT1-R mRNA stability, suggesting that the suppression
occurs at the transcriptional level.
Conclusions—PPAR activators reduced the
AT1-R expression and calcium response to Ang II in VSMCs.
Downregulation of AT1-R may contribute to the inhibition of
neointimal formation by PPAR activators.
Key Words: receptors • prostaglandins • troglitazone • angiotensin • muscle, smooth • cells
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