Expression of tumor necrosis factor-alpha--converting enzyme and tumor necrosis factor-alpha in human myocarditis.
OBJECTIVE
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.
Satoh
M
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine, Japan. satohm@iwate-med.ac.jp
Nakamura
M
M
Satoh
H
H
Saitoh
H
H
Segawa
I
I
Hiramori
K
K
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D015342:DNA Probes / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009205:Myocarditis / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D015342:DNA Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human