PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats.
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.
Lim
Soo
S
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
Jin
Cheng Ji
CJ
Kim
Min
M
Chung
Sung Soo
SS
Park
Ho Seon
HS
Lee
In Kyu
IK
Lee
Choon Taek
CT
Cho
Young Min
YM
Lee
Hong Kyu
HK
Park
Kyong Soo
KS
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
D047495:PPAR gamma; D012333:RNA, Messenger