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

Background-Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 gamma activators on the expression of Ang II type 1 receptor (AT(1)-R) in cultured vascular smooth muscle cells (VSMCs). Methods and Results-AT(1)-R mRNA and AT(1)-R protein levels were determined by Northern blot analysis and radioligand binding assay, respectively. Natural PPAR gamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2), as well as Tro, reduced the AT(1)-R mRNA expression and the AT(1)-R protein level. The PPAR gamma activators also reduced the calcium response of VSMCs to Ang II. PPAR gamma activators suppressed the AT(1)-R promoter activity measured by luciferase assay but did not affect the AT(1)-R MRNA stability, suggesting that the suppression occurs at the transcriptional level. Conclusions-PPAR gamma activators reduced the AT(1)-R expression and calcium response to Ang II in VSMCs, Downregulation of AT(1)-R may contribute to the inhibition of neointimal formation by PPAR gamma activators.