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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:808.)
© 2006 American Heart Association, Inc.

Vascular Biology

PPAR Gene Transfer Sustains Apoptosis, Inhibits Vascular Smooth Muscle Cell Proliferation, and Reduces Neointima Formation After Balloon Injury in Rats

Soo Lim; Cheng Ji Jin; Min Kim; Sung Soo Chung; Ho Seon Park; In Kyu Lee; Choon Taek Lee; Young Min Cho; Hong Kyu Lee; Kyong Soo Park

From the Seoul National University College of Medicine, Department of Internal Medicine (S.L., C.J.J., M.K., S.S.C., H.S.P., C.T.L., Y.M.C., H.K.L., K.S.P); and Kyungpook National University School of Medicine (I.K.L), Korea.

Correspondence to Kyong Soo Park, MD, PhD, Seoul National University College of Medicine, Department of Internal Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea 110-744. E-mail kspark{at}snu.ac.kr

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

Methods and Results— To investigate the effect of PPAR gene modulation on neointima formation after balloon injury, we delivered adenoviral vectors expressing the wild-type (WT) dominant negative (DN) PPAR, or a control gene (ß-galactosidase [BG]) into carotid artery after balloon injury in rosiglitazone (a PPAR ligand)-treated (R+) (3 mg/kg/d) and nontreated (R–) rats. Two weeks after gene delivery, in both R+ and R– animals, the PPAR-WT gene transfer showed a significantly lower intima-media ratio (IMR) than control group. Moreover, the delivery of a PPAR-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 PPAR-WT gene transferred group than in the PPAR-DN group.

Conclusions— In vivo transfer of the PPAR-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 PPAR overexpression itself has a protective role against restenosis after balloon injury.

There is debate as to whether protective effect of PPAR ligands on atherosclerosis is dependant on the PPAR gene itself or other pathway. We found that transfer of the PPAR wild-type gene inhibited neointima formation after balloon injury, which indicates that PPAR overexpression itself has a protective role against restenosis.

Key Words: PPAR • vascular smooth muscle • neointima • proliferation • apoptosis

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