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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

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
2006-01-21
Publisher
American Heart Association
Citation
Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):808-13. Epub 2006 Jan 19.
Keywords
AnimalsBalloon DilatationCarotid Arteries/*pathology/physiopathologyCarotid Artery Injuries/genetics/pathology/prevention & controlCells, CulturedGene Expression RegulationGene Transfer TechniquesGenes, fosMalePPAR gamma/*geneticsRNA, Messenger/biosynthesis/geneticsRatsRats, Sprague-DawleyTunica Intima/pathology/physiopathologyCell MovementCell ProliferationMuscle, 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
DOI
https://doi.org/10.1161/01.ATV.0000204634.26163.a7
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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