title: PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats.
abstract: OBJECTIVE
  There is still debate as to whether antiatherosclerotic effect of PPARgamma ligands is dependant on PPARgamma gene itself or some other pathway.
  
  
  RESULTS
  To investigate the effect of PPARgamma gene modulation on neointima formation after balloon injury, we delivered adenoviral vectors expressing the wild-type (WT) dominant negative (DN) PPARgamma, or a control gene (beta-galactosidase [BG]) into carotid artery after balloon injury in rosiglitazone (a PPARgamma ligand)-treated (R+) (3 mg/kg/d) and nontreated (R-) rats. Two weeks after gene delivery, in both R+ and R- animals, the PPARgamma-WT gene transfer showed a significantly lower intima-media ratio (IMR) than control group. Moreover, the delivery of a PPARgamma-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 PPARgamma-WT gene transferred group than in the PPARgamma-DN group.
  
  
  CONCLUSIONS
  In vivo transfer of the PPARgamma-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 PPARgamma overexpression itself has a protective role against restenosis after balloon injury.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
authors.forename: Cheng Ji
authors.initials: CJ
authors.lastname: Jin
authors.forename: Min
authors.initials: M
authors.lastname: Kim
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Choon Taek
authors.initials: CT
authors.lastname: Lee
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology* / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D002404:Catheterization; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D016762:Genes, fos; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger