title: Direct antiatherosclerotic effects of PPAR agonists.
abstract: OBJECTIVE
  Peroxisome proliferator activated receptors (PPARs) are ligand-dependent transcription factors that mediate a range of important metabolic functions by transactivation, transrepression or corepression of various gene targets. PPAR agonists also have direct antiatherosclerotic effects, independent of their metabolic effects on glucose and lipid homeostasis. The purpose of this review is to evaluate the currently available evidence for a direct vasculoprotective effect of PPAR agonists.
  
  
  RESULTS
  Current studies have emphasized PPAR-mediated effects on inflammatory and immune responses, oxidative stress, the renin-angiotensin system and modulation of plaque composition. Furthermore, it has become evident that the relative activation of the different PPAR isoforms and the contribution of transactivation of target genes against transrepression of transcription factors need to be considered when assessing the vasculoprotective effects of PPAR agonists.
  
  
  CONCLUSIONS
  It is anticipated that the antiatherosclerotic effects of PPAR agonists observed in experimental studies will translate into reduced cardiovascular events. This promise is yet to be realized in short-to-medium term studies. Given the central role of the PPAR in gene regulation, particularly in metabolic states, it is possible that more targeted modulation of PPAR signalling may hold many rewards for the prevention of atherosclerosis.
authors.affiliation: Diabetes Division, Albert Einstein JDRF Centre for Diabetes Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. Karin.jandeleit-dahm@bakeridi.edu.au
authors.forename: Karin A M
authors.initials: KA
authors.lastname: Jandeleit-Dahm
authors.forename: Anna
authors.initials: A
authors.lastname: Calkin
authors.forename: Chris
authors.initials: C
authors.lastname: Tikellis
authors.forename: Merlin
authors.initials: M
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D000069437:Pharmacological Phenomena; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms