Tumor Necrosis Factor-α–Converting Enzyme and Tumor Necrosis Factor-α in Human Dilated Cardiomyopathy

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Abstract
Background—Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). TNF-α–converting enzyme (TACE) has recently been purified and its complementary DNA cloned. The expression of TACE results in the production of a functional enzyme that has precursor TNF-α in the mature form. The aim of this study was to determine whether TACE is expressed with TNF-α in myocardium and whether levels of TACE and TNF-α are related to clinical severity of DCM. Methods and Results—Endomyocardial tissues were obtained from 30 patients with DCM and 5 control subjects. TNF-α and TACE mRNA levels were measured by a novel real-time quantitative reverse transcriptase–polymerase chain reaction method. Expression of TNF-α and TACE proteins was determined by immunohistochemical analysis. TNF-α mRNA was expressed in DCM patients (TNF-α/GAPDH ratio 0.85±0.24) but not in control subjects. TACE mRNA expression was significantly greater in DCM patients than in control subjects (TACE/GAPDH rat...