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CD36-mediated cholesterol efflux is associated with PPARγ activation via a MAPK-dependent COX-2 pathway in macrophages

Bujold, Kim, Rhainds, David, Jossart, Christian, Febbraio, Maria, Marleau, Sylvie, Ong, Huy·2009·Cardiovascular Research
DOI 10.1093/cvr/cvp118
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Abstract

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 (PPARgamma)-liver X receptor alpha (LXRalpha)-ATP-binding cassette (ABC) transporter pathway. However, the mechanism involved in PPARgamma 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 PPARgamma 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 PPARgamma. 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 cyclooxygenase-2 (COX-2) expression, leading to PPARgamma activation. In agreement, EP 80317-mediated cholesterol efflux was abrogated by inhibitors of PPARgamma, ERK1/2, and COX-2 as well as ABC transporter inhibitors, whereas a p38 mitogen-activated protein kinase inhibitor had no effect. Conclusion…

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Metadata

Authors
Bujold, K., Rhainds, D., Jossart, C., Febbraio, M., Marleau, S., & Ong, H.
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2009-04-17
Volume
83
Issue
3
Pages
457-464
ISSN
  • 1755-3245
  • 0008-6363
DOI
10.1093/cvr/cvp118
Cited by
54
References
1
Language
en

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