Modulation of vascular inflammation by PPARs.
The activation of cells in atherosclerotic lesions leads to the release of proinflammatory molecules and the onset of a chronic inflammatory response. Recent evidence suggests that peroxisome proliferator-activated receptors (PPARs) exert their antiinflammatory activities in vascular and immunological cell types such as endothelial cells, vascular smooth muscle cells and monocytes/macrophages. In these cells, PPARs regulate the gene expression of key proteins involved in the vascular inflammation contributing to atherogenesis. By modulating transcription of proinflammatory genes such as cytokines, chemokines, endothelial cell adhesion molecules and metalloproteinases, one can affect the events involved in atherogenesis, such as monocyte/macrophage and lymphocyte recruitment to the arterial wall and foam cell formation. Thus, PPAR agonists have emerged as a potential tool to modulate the inception and progression of atherosclerosis by exerting direct antiinflammatory and antiatherogenic actions at the level of the arterial wall. In this review, we will describe the current understanding of PPARs, the antiinflammatory activities of PPAR agonists and their proposed mechanisms of action.
Tham
Doris M
DM
Department of Internal Medicine, School of Medicine, University of California at Davis, USA. doris.tham@stanfordalumni.org
Wang
Yi-Xin
YX
Rutledge
John C
JC
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D001167:Arteritis / Q000188:drug therapy / Q000378:metabolism*; D002986:Clinical Trials as Topic; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000804:Angiotensin II