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PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats
Cited 54 time in
Web of Science
Cited 56 time in Scopus
- Authors
- Issue Date
- 2006-01-21
- Publisher
- American Heart Association
- Citation
- Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):808-13. Epub 2006 Jan 19.
- Keywords
- Animals ; Balloon Dilatation ; Carotid Arteries/*pathology/physiopathology ; Carotid Artery Injuries/genetics/pathology/prevention & control ; Cells, Cultured ; Gene Expression Regulation ; Gene Transfer Techniques ; Genes, fos ; Male ; PPAR gamma/*genetics ; RNA, Messenger/biosynthesis/genetics ; Rats ; Rats, Sprague-Dawley ; Tunica Intima/pathology/physiopathology ; Cell Movement ; Cell Proliferation ; Muscle, Smooth, Vascular/pathology/physiopathology
- Abstract
- 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.
- ISSN
- 1524-4636 (Electronic)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16424348
https://hdl.handle.net/10371/44033
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