title: Simvastatin decreases myocardial tumor necrosis factor alpha content in heart transplant recipients.
abstract: BACKGROUND
  Statins improve patient survival and decrease rejection episodes in heart transplant recipients. We studied the effects of simvastatin treatment on myocardial tumor necrosis factor alpha (TNF-alpha) expression; TNF-alpha is a potent pro-inflammatory cytokine associated with hypertrophy and fibrosis in heart transplant recipients.
  
  
  METHODS
  We randomized 10 consecutive heart transplant recipients to receive either 20 mg/day simvastatin (n = 5) or placebo (n = 5) for 6 months after cardiac transplantation. Routine surveillance endomyocardial biopsy specimens were obtained from all patients. We analyzed tissues for myocardial TNF-alpha content, total collagen content, and myocyte size using semiquantitative immunohistochemistry.
  
  
  RESULTS
  Myocyte size and total collagen content of placebo and simvastatin groups did not show a statistically significant difference at any biopsy time point. Myocardium TNF-alpha content (% tissue area stained) at 1 week after transplantation was similar in the simvastatin and placebo groups. At the 24(th) week after transplantation, when compared with Week 1 values, we found a significant decrease in myocardium TNF-alpha content in the simvastatin group (15.0% +/- 2.3% vs 5.8% +/- 2.4%, p = 0.02) that was not observed in the placebo group (15.0% +/- 1.5% vs 12.0% +/- 2.6%, p = not significant).
  
  
  CONCLUSIONS
  Simvastatin treatment in heart transplant recipients decreased myocardium TNF-alpha expression. This decrease did not translate into a difference in the markers of hypertrophy. However, decreased myocardial TNF-alpha may be a marker of a general statin-mediated decrease in inflammation in the transplanted heart that leads to improved graft and patient survival.
authors.affiliation: Baylor College of Medicine, 6550 Fannin, Houston, Texas 77030, USA.
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Wallace
authors.forename: Sonny J
authors.initials: SJ
authors.lastname: Stetson
authors.forename: Seref A
authors.initials: SA
authors.lastname: Küçüker
authors.forename: Katy A
authors.initials: KA
authors.lastname: Becker
authors.forename: John A
authors.initials: JA
authors.lastname: Farmer
authors.forename: Susan C
authors.initials: SC
authors.lastname: McRee
authors.forename: Michael M
authors.initials: MM
authors.lastname: Koerner
authors.forename: George P
authors.initials: GP
authors.lastname: Noon
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000378:metabolism / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006984:Hypertrophy / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin