Objective— There is still debate as to whether antiatherosclerotic effect of PPARγ ligands is dependant on PPARγ gene itself or some other pathway.

Methods and Results— To investigate the effect of PPARγ gene modulation on neointima formation after balloon injury, we delivered adenoviral vectors expressing the wild-type (WT) dominant negative (DN) PPARγ, or a control gene (β-galactosidase [BG]) into carotid artery after balloon injury in rosiglitazone (a PPARγ ligand)-treated (R+) (3 mg/kg/d) and nontreated (R−) rats. Two weeks after gene delivery, in both R+ and R− animals, the PPARγ-WT gene transfer showed a significantly lower intima-media ratio (IMR) than control group. Moreover, the delivery of a PPARγ-DN form showed the highest IMR (in R+WT, 0.51±0.15; R+BG, 0.89±0.14; R+DN, 1.20±0.18, P<0.05 and in R−WT, 0.91±0.21; R−BG, 1.44±0.23; R−DN, 1.74±0.29, P<0.05). Proliferation and migration showed same result pattern as IMR. In addition, apoptotic indices were significantly higher in the PPARγ-WT gene transferred group than in the PPARγ-DN group.

Conclusions— In vivo transfer of the PPARγ-WT gene was found to inhibit smooth muscle proliferation, sustain apoptosis, and reduce neointima formation after balloon injury irrespective of rosiglitazone treatment. These results indicate that PPARγ overexpression itself has a protective role against restenosis after balloon injury.