The role of PPARs in atherosclerosis

被引:209
作者
Duval, C
Chinetti, G
Trottein, F
Fruchart, JC
Staels, B [1 ]
机构
[1] Inst Pasteur, U545 INSERM, Dept Atherosclerose, F-59019 Lille, France
[2] Univ Lille 2, Fac Pharm, Lille, France
[3] Inst Pasteur, U547 INSERM, Ctr Immunol & Biol Parasitaire, Lille, France
关键词
D O I
10.1016/S1471-4914(02)02385-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 PPARalpha 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 PPARalphad 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 PPARalpha, PPARbeta/delta and/or PPARgamma as well as tissue and target gene-selective PPAR receptor modulators (SPPARMs).
引用
收藏
页码:422 / 430
页数:9
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