S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Genomic Medicine (분자유전체의학전공) Journal Papers (저널논문_분자유전체의학전공)
PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats
- Lim, Soo; Jin, Cheng Ji; Kim, Min; Chung, Sung Soo; Park, Ho Seon; Lee, In Kyu; Lee, Choon Taek; Cho, Young Min; Lee, Hong Kyu; Park, Kyong Soo
- Issue Date
- American Heart Association
- Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):808-13. Epub 2006 Jan 19.
- Animals; Balloon Dilatation; Carotid Arteries/*pathology/physiopathology; Carotid Artery Injuries/genetics/pathology/prevention & control; *Cell Movement; *Cell Proliferation; Cells, Cultured; Gene Expression Regulation; Gene Transfer Techniques; Genes, fos; Male; *Muscle, Smooth, Vascular/pathology/physiopathology; PPAR gamma/*genetics; RNA, Messenger/biosynthesis/genetics; Rats; Rats, Sprague-Dawley; Tunica Intima/pathology/physiopathology
- OBJECTIVE: There is still debate as to whether antiatherosclerotic effect of PPARgamma ligands is dependant on PPARgamma gene itself or some other pathway. METHODS AND 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.
- 1524-4636 (Electronic)