Zeitschrift für Kardiologie

, Volume 90, Supplement 3, pp 125–132

Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall

  • G. Chinetti
  • J.-C. Fruchart
  • B. Staels

DOI: 10.1007/s003920170034

Cite this article as:
Chinetti, G., Fruchart, J. & Staels, B. Z Kardiol (2001) 90: 125. doi:10.1007/s003920170034

Summary

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPARα is highly expressed in liver, muscle, kidney and heart, where it stimulates the β:-oxidative degradation of fatty acids. PPARγ is predominantly expressed in intestine and adipose tissue when it triggers adipocyte differentiation and promotes lipid storage. Recently, the expression of PPARα and PPARγ was also reported in cells of the vascular wall, such as monocyte/macrophages, endothelial and smooth muscle cells. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPARα and PPARγ respectively. Furthermore, fatty acid-derivatives and eicosanoids are natural PPAR ligands: PPARα is activated by leukotriene B4, whereas prostaglandin J2 is a PPARγ ligand, as well as some components of oxidized LDL, such as 9- and 13-HODE. These observations suggested a potential role for PPARs not only in metabolic but also in inflammation control and, by consequence, in related diseases such as atherosclerosis. More recently, PPAR activators were shown to inhibit the activation of inflammatory response genes (such as IL-2, IL-6, IL-8, TNFα and metalloproteases) by negatively interfering with the NF-κB, STAT and AP-1 signalling pathways in cells of the vascular wall. Furthermore, PPARs may also control lipid metabolism in the cells of the atherosclerotic plaque. In addition, different clinical trials (such as the LOCAT, BECAIT and VA-HIT) as well as animal studies indicate that PPAR activators may have anti-atherogenic properties by reducing the progression of atherosclerotic lesions. In this review, we summarize the evidence indicating that PPARα and PPARγ directly modulate vessel wall functions, and its consequences in the control of cardiovascular disease.

Key words Transcription factors – gene expression – macrophage – endothelial cell – smooth muscle cell
Abbreviations AP-1: activating protein-1; Apo: apolipoprotein; NFAT: nuclear factor of activated T cells; NSAIDs: non-steroidal antiinflammatory drugs; PPAR: peroxisome proliferator-activated receptor; PPRE: peroxisome proliferator response element; RXR: retinoid X receptor; STAT: signal transducer and activator of transcription.

Copyright information

© Steinkopff Verlag 2001

Authors and Affiliations

  • G. Chinetti
    • 1
  • J.-C. Fruchart
    • 1
  • B. Staels
    • 1
  1. 1.U.325 Inserm, Institut Pasteur de Lille, 1, rue Calmette BP245, 59019 Lille, France, E-mail: bart.staels@pasteur-lille.frFR