title: PPARs as therapeutic targets in cardiovascular disease.
abstract: BACKGROUND
  The role of peroxisome proliferator-activated receptors PPARα, PPARδ and PPARγ in cardiovascular disease is receiving widespread attention. As ligand-activated nuclear receptors, they play a role in regulation of lipid and glucose metabolism. This feature of the PPARs has been successfully exploited to treat systemic metabolic diseases, like hyperlipidemia and type-2 diabetes. Indirectly, their lipid lowering effect also leads to a reduction of the risk for cardiovascular diseases, primarily atherosclerosis.
  
  
  METHODS
  The pleiotropic effects of each of the PPAR isotypes on vascular and cardiac disease are discussed, with special emphasis on the molecular mechanism of action and on preclinical observations. The mechanism underlying the beneficial effect of PPARs is not confined to whole body metabolism, but also includes modulation of other vital processes, such as inflammation and cell fate (proliferation, differentiation, apoptosis).
  
  
  RESULTS
  A large body of preclinical studies indicates that, in addition to their effect on atherogenesis, PPAR ligands also impact on ischemic heart disease and the development of cardiac failure. It remains to be established to what extent these intriguing observations can be translated into clinical practice.
  
  
  CONCLUSIONS
  The versatile mechanism of action extends the potential therapeutic profile of the PPARs enormously. Conversely, this versatility makes it harder to attain a specific therapeutic effect, without increasing the risk of undesirable side effects. The future challenge will be to design PPAR-based therapeutic strategies that minimize the detrimental side effects.
authors.affiliation: Maastricht University, Cardiovascular Research Institute Maastricht, Department of Physiology, 6200 MD Maastricht, The Netherlands. Marc.vanBilsen@FYS.Unimaas.NL
authors.forename: Marc
authors.initials: M
authors.lastname: van Bilsen
authors.forename: Frans A
authors.initials: FA
authors.lastname: van Nieuwenhoven
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008024:Ligands; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism
chemical_list: D008024:Ligands; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors