The role of PPARs in atherosclerosis.
Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that regulate lipid and lipoprotein metabolism, glucose homeostasis and inflammation. The PPAR family consists of three proteins, alpha, beta/delta and gamma. Recent data suggest that PPAR alpha and gamma activation decreases atherosclerosis progression not only by correcting metabolic disorders, but also through direct effects on the vascular wall. PPARs modulate the recruitment of leukocytes to endothelial cells, control the inflammatory response and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine production by smooth muscle cells. Experiments using animal models of atherosclerosis and clinical studies in humans strongly support an anti-atherosclerotic role for PPAR alpha and gamma in vivo. Thus, PPARs remain attractive therapeutic targets for the development of drugs used in the treatment of chronic inflammatory diseases such as atherosclerosis. Future research will aim for the development of more potent drugs with co-agonist activity on PPAR alpha, PPAR beta/delta and/or PPAR gamma as well as tissue and target gene-selective PPAR receptor modulators (SPPARMs).
Duval
Caroline
C
U545 INSERM, Dépt d'Athérosclérose, Institut Pasteur de Lille, and Faculté de Pharmacie, Université de Lille II, Lille, France
Chinetti
Giulia
G
Trottein
Francois
F
Fruchart
Jean-Charles
JC
Staels
Bart
B
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D050356:Lipid Metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D000209:Acute-Phase Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D002784:Cholesterol