Key result
Dilated cardiomyopathy is linked to markedly higher myocardial TACE mRNA expression vs controls.
Why the study?
Tumor necrosis factor-alpha (TNF-alpha) and its converting enzyme (TACE) have been implicated in dilated cardiomyopathy, but their myocardial expression and relation to clinical severity were unclear.
Case-Control (n=35)
Absolute Event Rate: 2.52% vs 0.03%
p-value: p=<0.05
Increased myocardial TACE expression is associated with elevated TNF-alpha expression and correlates with clinical severity (lower LVEF and higher LVESD) in patients with dilated cardiomyopathy.
Supports TACE as a potential TNF-alpha mediator in DCM; hypothesis-generating for targeted inhibition.
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). TNF-alpha-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-alpha in the mature form. The aim of this study was to determine whether TACE is expressed with TNF-alpha in myocardium and whether levels of TACE and TNF-alpha are related to clinical severity of DCM. METHODS AND RESULTS: Endomyocardial tissues were obtained from 30 patients with DCM and 5 control subjects. TNF-alpha and TACE mRNA levels were measured by a novel real-time quantitative reverse transcriptase-polymerase chain reaction method. Expression of TNF-alpha and TACE proteins was determined by immunohistochemical analysis. TNF-alpha mRNA was expressed in DCM patients (TNF-alpha/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 ratio 2.52+/-0.59 vs 0.03+/-0.02, P<0.05). A positive correlation was found between TNF-alpha and TACE mRNA levels (r=0.779, P<0.001). TACE and TNF-alpha immunostaining was observed in myocytes in patients with DCM. When 2 subgroups of DCM were divided on the basis of left ventricular end-systolic diameter (LVESD) of 45 mm and left ventricular ejection fraction (LVEF) of 40%, the DCM subgroup with high LVESD (>/=45 mm) showed significantly greater expression of TACE (P=0.02) and TNF-alpha (P=0. 001) than did the low LVESD subgroup (<45 mm). In addition, the DCM subgroup with lower LVEF (<40%) showed higher expression of TACE (P=0.006) and TNF-alpha (P=0.01) than did the subgroup with high LVEF (>/=40%). CONCLUSIONS: This study has shown that increased myocardial TACE expression is associated with elevated myocardial TNF-alpha expression in both mRNA and protein levels in clinically advanced DCM.
No takes yet. Share an insight, caveat, or question.
Satoh et al. (1999) conducted a case-control in Dilated Cardiomyopathy (n=35). Dilated Cardiomyopathy vs. Control subjects was evaluated on TACE mRNA expression (TACE/GAPDH ratio) (p=<0.05). Patients with dilated cardiomyopathy had significantly greater myocardial TACE mRNA expression than control subjects (TACE/GAPDH ratio 2.52 vs 0.03, P<0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: