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

Background-Peroxisome proliferator-activated receptor gamma (PPAR gamma) ac tivators, such as troglitazone (Tro), not only improve insulin resistance b ut also suppress the neointimal formation after balloon injury. However, th e precise mechanisms have not been determined. Angiotensin II (Ang II) play s crucial roles in the pathogenesis of atherosclerosis, hypertension, and n eointimal formation after angioplasty. We examined the effect of PPAR gamma activators on the expression of Ang II type 1 receptor (AT(1)-R) in cultur ed 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. Nat ural 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. Th e PPAR gamma activators also reduced the calcium response of VSMCs to Ang I I. PPAR gamma activators suppressed the AT(1)-R promoter activity measured by luciferase assay but did not affect the AT(1)-R MRNA stability, suggesti ng that the suppression occurs at the transcriptional level. Conclusions-PPAR gamma activators reduced the AT(1)-R expression and calciu m response to Ang II in VSMCs, Downregulation of AT(1)-R may contribute to the inhibition of neointimal formation by PPAR gamma activators.