Expression of tumor necrosis factor-alpha-converting enzyme and tumor necrosis factor-alpha in human myocarditis

OBJECTIVES We determined whether tumor necrosis factor-alpha-converting enzyme (TACE) is expressed with tumor necrosis factor-alpha (TNF-alpha) in myocarditis. BACKGROUND Tumor necrosis factor-alpha-converting enzyme, which has recently been identified as belonging to the family of metalloproteinase disintegrin proteins, is responsible for the conversion of TNF-alpha precursor to its mature form. METHODS We examined TACE and TNF-alpha expressions in endomyocardial biopsy tissues obtained from 14 patients with myocarditis and five control subjects by using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS Expression of TNF alpha and TACE messenger ribonucleic acid (mRNA) was significantly greater in the myocarditis group than in the control group. A positive correlation was found between TNF-alpha and TACE mRNAs (r = 0.83, p < 0.05). Six patients with severe myocarditis underwent repeat biopsies. Although TNF-alpha and TACE mRNAs were expressed at high levels in the initial biopsies, a marked decrease was noted in the repeat biopsies. The immunostainings for TNF-alpha and TACE were positive in the myocytes and interstitial cells of myocardium obtained from patients with myocarditis. Expression of TACE and TNF-alpha mRNAs was greater in the subgroup in New York Heart Association functional class III or IV than in the subgroup in class I or II. Expression of TACE and TNF-alpha mRNA was correlated positively with left ventricular volume (TNF-alpha: r = 0.85; TACE: r = 0.80) and negatively with left ventricular systolic function (TNF-alpha: r = -0.85; TACE: r = -0.85). CONCLUSIONS These findings indicate that the expression of TNF-alpha and TACE may have important implications in the pathogenesis of myocarditis and may influence advanced cardiac dysfunction in myocarditis. (T Am Coil Cardiol 2000;36:1288-94) (C) 2000 by the American College of Cardiology.