PPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis

Yasunori Takata, Joey Liu, Fen Yin, Alan R. Collins, Christopher J. Lyon, Chih Hao Lee, Annette R. Atkins, Michael Downes, Grant D. Barish, Ronald M. Evans, Willa A. Hsueh, Rajendra K. Tangirala

Research output: Contribution to journalArticlepeer-review

177 Scopus citations


Activation of the nuclear hormone receptor peroxisome proliferator- activated receptor δ (PPARδ) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPARδ activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPARδ agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RGS4, and RGS5, which was associated with suppression of inflammatory and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated macrophages: PPARδ activation increased both total and free Bcl-6 levels and inhibited AngII activation of MAP kinases, p38, and ERK1/2. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of PPARδ activation to inhibit AngII signaling, which is atheroprotective.

Original languageEnglish (US)
Pages (from-to)4277-4282
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - Mar 18 2008


  • Macrophage
  • Peroxisome proliferator-activated receptor δ
  • Vascular inflammation

ASJC Scopus subject areas

  • General


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