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CLINICAL STUDY: HEART FAILURE

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

^a Second Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan
^* Second Department of Pathology, Iwate Medical University School of Medicine, Iwate, Japan

Manuscript received December 3, 1999; revised manuscript received March 21, 2000, accepted May 1, 2000.

Reprint requests and correspondence: Dr. Mamoru Satoh, Second Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Iwate, Japan
satohm{at}iwate-med.ac.jp

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.

Abbreviations and Acronyms   cDNA = complementary deoxyribonucleic acid   CK = creatine kinase   GAPDH = glyceraldehyde-3-phosphate dehydrogenase   mRNA = messenger ribonucleic acid   NYHA = New York Heart Association   RT-PCR = reverse transcriptase polymerase chain reaction   TACE = tumor necrosis factor-alpha–converting enzyme   TNF-alpha = tumor necrosis factor-alpha

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