title: Novel benefits of peroxisome proliferator-activated receptors on cardiovascular risk.
abstract: OBJECTIVE
  This review provides an overview of newly described mechanisms by which peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ) regulate several factors associated with cardiovascular risk.
  
  
  RESULTS
  PPAR agonists have known effects on plasma lipoprotein levels, inflammation, and insulin resistance all of which influence the risk of cardiovascular disease. Recent studies provide more detail regarding the mechanisms behind these changes. PPAR-α activation in the enterocyte on HDL and chylomicron formation. PPAR-γ agonists reduce inflammation, in part, through direct effects on adipocytes and regulatory T cells within visceral adipose. PPAR-δ also has a relatively high expression in the macrophage. Incubation of macrophages with PPAR-δ agonists was shown to inhibit foam cell formation induced excessive levels of VLDL remnants.
  
  
  CONCLUSIONS
  Treatments that activate PPAR-α, PPAR-γ, and PPAR-δ alone or in combination have the potential to reduce cardiovascular risk although multiple independent mechanisms. Treatment with PPAR agonists can reduce the burden of atherogenic postprandial lipoproteins and improve vascular function, reduce inflammation and inhibit foam cell formation. All of these would be expected to have favorable effects on cardiovascular risk. The challenge remains to develop compounds that maximize these potential cardiovascular benefits while minimizing undesirable effects of these compounds.
authors.affiliation: Division of Translational Medicine and Human Genetics, Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania, USA. jsmillar@upenn.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Millar
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011345:Fenofibrate / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D000960:Hypolipidemic Agents; D008074:Lipoproteins; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D045162:Thiazolidinediones; D011345:Fenofibrate