title: PPARγ in coronary atherosclerosis: in vivo expression pattern and correlations with hyperlipidemic status and statin treatment.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in regulation of macrophage inflammation and in atherosclerosis. Herein we investigate the influence of statin treatment on PPARγ expression in coronary artery disease.
  
  
  METHODS
  PPARγ expression was investigated in coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients with stable or unstable coronary syndromes or undergoing cardiac transplantation for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry. Plaque components and tissue factor immunoreactivity were also investigated. Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients. Furthermore, PPARγ expression was evaluated in patients peripheral blood monocytes and in monocytic U937 cells after atorvastatin incubation, by Western blot analysis.
  
  
  RESULTS
  PPARγ expression was higher in coronary plaques and peripheral blood monocytes of statin-treated patients, and it significantly increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP levels were lower in statin-treated than untreated hypercholesterolemic patients and comparable with normolipidemic subjects. PPARγ immunoreactivity was localized to neointima and media, its distribution pattern being different from that of tissue factor.
  
  
  CONCLUSIONS
  PPARγ expression was enhanced in statin-treated patients with different distribution and behavior as compared to atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In vitro studies showed increased PPARγ expression in monocytes after atorvastatin incubation. These findings provide further evidence as to the protective role of statins in coronary artery disease and their influence on PPARγ expression in coronary plaques and on the inflammatory status of patients.
authors: Department of Anatomic, Ultrastructural and Molecular Pathology, Pisa University Hospital, Pisa, Italy. angelapucci@libero.it
authors: Angela
authors: A
authors: Pucci
authors: Luisa
authors: L
authors: Formato
authors: Maruska
authors: M
authors: Muscio
authors: Elvis
authors: E
authors: Brscic
authors: Stefania
authors: S
authors: Pizzimenti
authors: Francesca
authors: F
authors: Ferroni
authors: Marco
authors: M
authors: Ribezzo
authors: Cristina
authors: C
authors: Toaldo
authors: Piergiorgio
authors: P
authors: Pettazzoni
authors: Eric
authors: E
authors: Ciamporcero
authors: Giuseppina
authors: G
authors: Barrera
authors: Mauro
authors: M
authors: Rinaldi
authors: Laura
authors: L
authors: Bergamasco
authors: Imad
authors: I
authors: Sheiban
authors: Maria Teresa
authors: MT
authors: Spinnler
mesh_terms: D000328:Adult; D000368:Aged; D001158:Arteries / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism; D020298:U937 Cells
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047495:PPAR gamma