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-Δ^12,14-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.