Simvastatin decreases myocardial tumor necrosis factor α content in heart transplant recipients

Cynthia K. Wallace, Sonny J. Stetson, Seref A. Küçüker, Katy A. Becker, John A. Farmer, Susan C. McRee, Michael M. Koerner, George P. Noon, Guillermo Torre

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 α (TNF-α) expression; TNF-α 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-α 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-α content (% tissue area stained) at 1 week after transplantation was similar in the simvastatin and placebo groups. At the 24th week after transplantation, when compared with Week 1 values, we found a significant decrease in myocardium TNF-α 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). Conclusion Simvastatin treatment in heart transplant recipients decreased myocardium TNF-α expression. This decrease did not translate into a difference in the markers of hypertrophy. However, decreased myocardial TNF-α may be a marker of a general statin-mediated decrease in inflammation in the transplanted heart that leads to improved graft and patient survival.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2005

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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