Peroxisome proliferator-activated receptor γ activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells

Kotaro Takeda, Toshihiro Ichiki, Tomotake Tokunou, Yuko Funakoshi, Naoko Iino, Katsuya Hirano, Hideo Kanaide, Akira Takeshita

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Background - Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2, as well as Tro, reduced the AT1-R mRNA expression and the AT1-R protein level. The PPARγ activators also reduced the calcium response of VSMCs to Ang II. PPARγ 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 - PPARγ 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 PPARγ activators.

Original languageEnglish
Pages (from-to)1834-1839
Number of pages6
JournalCirculation
Volume102
Issue number15
DOIs
Publication statusPublished - Oct 10 2000

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Angiotensin Type 1 Receptor
Peroxisome Proliferator-Activated Receptors
Vascular Smooth Muscle
Smooth Muscle Myocytes
Down-Regulation
troglitazone
Angiotensin II
Calcium-Sensing Receptors
Radioligand Assay
Messenger RNA
RNA Stability
Luciferases
Angioplasty
Northern Blotting
Insulin Resistance
Atherosclerosis
Proteins
Ligands
Hypertension
Calcium

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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Peroxisome proliferator-activated receptor γ activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. / Takeda, Kotaro; Ichiki, Toshihiro; Tokunou, Tomotake; Funakoshi, Yuko; Iino, Naoko; Hirano, Katsuya; Kanaide, Hideo; Takeshita, Akira.

In: Circulation, Vol. 102, No. 15, 10.10.2000, p. 1834-1839.

Research output: Contribution to journalArticle

Takeda, Kotaro ; Ichiki, Toshihiro ; Tokunou, Tomotake ; Funakoshi, Yuko ; Iino, Naoko ; Hirano, Katsuya ; Kanaide, Hideo ; Takeshita, Akira. / Peroxisome proliferator-activated receptor γ activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. In: Circulation. 2000 ; Vol. 102, No. 15. pp. 1834-1839.
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