JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 20, 2005; DOI: 10.1124/jpet.105.095125

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.105.095125v1
317/1/37    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, K.
Right arrow Articles by Penn, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, K.
Right arrow Articles by Penn, M. S.


Received for publication September 2, 2005.
Revised December 16, 2005.
Accepted for publication December 19, 2005.

Peroxisome Proliferator-Activated Receptor Gamma Down-Regulates Receptor for Advanced Glycation End Products and Inhibits Smooth Muscle Cell Proliferation in a Diabetic and Non-diabetic Rat Carotid Artery Injury Model

Kai Wang 1*, Zhongmin Zhou 1, Ming Zhang 1, Liming Fan 1, Farhad Forudi 1, Xiaorong Zhou 1, Wu Qu 2, A . Michael Lincoff 1, Ann Marie Schmidt 3, Eric J. Topol 4, Marc S. Penn 1

1 The Cleveland Clinic Foundation 2 College of Physicians & Surgeons, 3 College of Physicians & Surgeons 4 The Cleveland Clinic Foundation, Cleveland

* Address correspondence to: E-mail: wangk{at}ccf.org

Abstract

Diabetes is associated with an increase in circulating advanced glycosylation end-products (AGEs) and the increased expression of the receptor for AGEs (RAGE). Inhibition of AGE:RAGE binding through the administration of soluble RAGE (sRAGE) has been shown to decrease neointimal hyperplasia. Peroxisome proliferator-activated receptor {gamma}(PPAR {gamma}), which inhibits neointimal hyperplasia, has been shown to decrease RAGE expression in cultured endothelial cells. We hypothesized that PPAR{gamma} agonists inhibit neointimal hyperplasia via down-regulation of RAGE in vivo. Methods and Results. Pretreatment of rat aortic smooth muscle cells (SMCs) with PPAR{gamma} agonist rosiglitazone significantly down-regulated RAGE expression and inhibited SMC proliferation in response to the RAGE agonist S100. In vivo studies showed that rosiglitazone decreased RAGE expression and SMC proliferation at 7 days following carotid arterial injury in both diabetic and non-diabetic rats. At 21 days following injury, neointimal formation was significantly decreased in both diabetic and non-diabetic animals that received rosiglitazone. To determine if inhibition of neointimal formation by PPAR{gamma} activation could fully be accounted for by its down-regulation of RAGE, we compared the results obtained in animals treated with sRAGE, PPAR{gamma} activator, and sRAGE+PPAR{gamma} activator. Consistent with PPAR{gamma} working through its effects on RAGE, we found that the addition of PPAR{gamma} activator to sRAGE did not result in any further decrease in neointimal formation. Conclusion. These data demonstrate for the first time that PPAR{gamma} agonists inhibit RAGE expression at sites of arterial injury, and suggest that down-regulation of RAGE by the PPAR{gamma} activation inhibits neointimal formation in response to arterial injury.


Key words: PPAR, RAGE, animal model, arterial injury, inflammation, restenosis


This article has been cited by other articles:


Home page
 Circ. Res.Home page
E. Caglayan and S. Rosenkranz
Living on the Edge: Hypoxia-Induced Tissue Damage
Circ. Res., April 25, 2008; 102(8): 864 - 865.
[Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Joner, A. Farb, Q. Cheng, A. V. Finn, E. Acampado, A. P. Burke, K. Skorija, W. Creighton, F. D. Kolodgie, H. K. Gold, et al.
Pioglitazone Inhibits In-Stent Restenosis in Atherosclerotic Rabbits by Targeting Transforming Growth Factor-{beta} and MCP-1
Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 182 - 189.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.