Peroxisome proliferator-activated receptor-γ-mediated effects in the vasculature

Sheng Zhong Duan, Michael G. Usher, Richard M. Mortensen

Research output: Contribution to journalReview articlepeer-review

214 Scopus citations

Abstract

Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear receptor and transcription factor in the steroid superfamily. PPAR-γ agonists, the thiazolidinediones, are clinically used to treat type 2 diabetes. In addition to its function in adipogenesis and increasing insulin sensitivity, PPAR-γ also plays critical roles in the vasculature. In vascular endothelial cells, PPAR-γ activation inhibits endothelial inflammation by suppressing inflammatory gene expression and therefore improves endothelial dysfunction. In vascular smooth muscle cells, PPAR-γ activation inhibits proliferation and migration and promotes apoptosis. In macrophages, PPAR-γ activation suppresses inflammation by regulating gene expression and increases cholesterol uptake and efflux. A recurring theme in many cell types is the modulation of the innate immunity system particularly through altering the activity of the nuclear factor κB. This system is likely to be even more prominent in modulating disease in vascular cells. The effects of PPAR-γ in the vascular cells translate into the beneficial function of this transcription factor in vascular disorders, including hypertension and atherosclerosis. Both human genetic studies and animal studies using transgenic mice have demonstrated the importance of PPAR-γ in these disorders. However, recent clinical studies have raised significant concerns about the cardiovascular side effects of thiazolidinediones, particularly rosiglitazone. Weighing the potential benefit and harm of PPAR-γ activation and exploring the functional mechanisms may provide a balanced view on the clinical use of these compounds and new approaches to the future therapeutics of vascular disorders associated with diabetes.

Original languageEnglish (US)
Pages (from-to)283-294
Number of pages12
JournalCirculation research
Volume102
Issue number3
DOIs
StatePublished - Feb 2008

Keywords

  • Macrophages
  • PPAR-γ, vascular endothelial cells
  • Vascular disorders
  • Vascular smooth muscle cells

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