Simvastatin decreases myocardial tumor necrosis factor alpha content in heart transplant recipients.
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.
Wallace
Cynthia K
CK
Baylor College of Medicine, 6550 Fannin, Houston, Texas 77030, USA.
Stetson
Sonny J
SJ
Küçüker
Seref A
SA
Becker
Katy A
KA
Farmer
John A
JA
McRee
Susan C
SC
Koerner
Michael M
MM
Noon
George P
GP
Torre-Amione
Guillermo
G
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*
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin