PPARS in inflammation, atherosclerosis and thrombosis.
PPARs are transcription factors which regulate lipid and lipoprotein metabolism, glucose homeostasis and cellular differentiation. PPARalpha enhances fatty acid oxidation whereas PPARgamma promotes adipogenesis and fatty acid storage in adipose tissue. Both PPARalpha and PPARgamma improve glucose homeostasis. PPARalpha and PPARgamma are activated by the pharmacological agents fibrates and glitazones respectively, and by natural fatty acid derivatives, including inflammation mediators. PPARs are expressed in the different cell types of human atherosclerotic lesions where they regulate the expression of genes involved in the inflammatory response and lipid homeostasis. PPARs modulate the recruitment and adhesion of leukocytes and monocytes to the atherosclerotic lesion. PPARs furthermore control macrophage lipid homeostasis through their action on scavenger receptors and by regulating genes involved in the first steps of the reverse cholesterol transport pathway. Finally, PPARs regulate genes controlling thrombogenicity associated with plaque rupture. These observations suggest that PPARs modulate atherosclerosis development by acting at both metabolic and vascular levels. This review will essentially focus on the functions of PPARalpha and PPARgamma in immunoregulation, vascular inflammation and thrombosis associated to atherosclerosis.
Duez
H
H
UR545 INSERM, Départment d'Athérosclérose, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille, France.
Fruchart
J C
JC
Staels
B
B
D001161:Arteriosclerosis / Q000503:physiopathology*; D007121:Immunocompetence; D007249:Inflammation / Q000503:physiopathology*; D008024:Ligands; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors