Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on April 17, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp118
This Article
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
83/3/457    most recent
cvp118v2
cvp118v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bujold, K.
Right arrow Articles by Ong, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bujold, K.
Right arrow Articles by Ong, H.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

CD36-mediated cholesterol efflux is associated with PPAR{gamma} activation via a MAPK-dependent COX-2 pathway in macrophages

Kim Bujold1, David Rhainds1,4, Christian Jossart1, Maria Febbraio3, Sylvie Marleau1 and Huy Ong1,2

1 Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada
2 Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada
3 Department of Cell Biology, Lerner Research Institute, Cleveland, OH, USA

Author for correspondence: Huy Ong, PhD, Faculty of Pharmacy, Université de Montréal, P.O. Box 6128, Station, Centre-Ville, Montréal, Québec, Canada, H3C 3J7; Fax: 514-343-2102, Tel: 514-343-6440; E-mail: huy.ong{at}umontreal.ca

Aims: Growth hormone-releasing peptides (GHRPs) as CD36 selective ligands feature potent anti-atherosclerotic activity that is associated with an upregulation of the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma})-liver X receptor {alpha} (LXR{alpha})-ATP-binding cassette (ABC) transporter pathway. However, the mechanism involved in PPAR{gamma} activation in response to CD36 signalling has yet to be determined. Therefore, the present study aims to elucidate the upstream molecular mechanisms through which EP 80317, a selective CD36 ligand, promotes lipid efflux from macrophages through PPAR{gamma} activation.

Methods and results: [3H]-cholesterol- and [3H]-methylcholine chloride-labelled murine macrophages treated with EP 80317 showed a significant increase in cholesterol and phospholipid efflux to both apolipoprotein A-I and high-density lipoprotein in a CD36-dependent manner. Lipid efflux was associated with enhanced activation of PPAR{gamma}. The signalling pathway by which this CD36 ligand promoted lipid efflux involved an increase in intracellular 15-deoxy-{Delta}12,14-prostaglandin J2 (15d-PGJ2) levels induced by extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent COX-2 expression, leading to PPAR{gamma} activation. In agreement, EP 80317-mediated cholesterol efflux was abrogated by inhibitors of PPAR{gamma}, ERK1/2 and COX-2 as well as ABC transporter inhibitors, whereas a p38 mitogen-activated protein kinase (MAPK) inhibitor had no effect.

Conclusion: These findings suggest a central role for the prostanoid 15d-PGJ2 in PPAR{gamma} activation and the upregulation of the ABC transporter pathway in response to CD36 activation by synthetic GHRPs analogues. The resulting enhanced cholesterol efflux might explain, at least in part, the atheroprotective effect of selective CD36 ligands.

KEYWORDS CD36; cholesterol efflux; COX-2; macrophages; PPAR{gamma}

Time for primary review: 26 Days

4 Present address: Genizon BioSciences Inc., St-Laurent, Québec, Canada


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related Article

Growth hormone-releasing peptides, CD36, and stimulation of cholesterol efflux: cyclooxygenase-2 is the link
Dipak P. Ramji
Cardiovasc Res 2009 83: 419-420. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
D. P. Ramji
Growth hormone-releasing peptides, CD36, and stimulation of cholesterol efflux: cyclooxygenase-2 is the link
Cardiovasc Res, August 1, 2009; 83(3): 419 - 420.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.