Activated tumour necrosis factor-α shedding process is associated with in-hospital complication in patients with acute myocardial infarction

Abstract

TACE [TNF-alpha (tumour necrosis factor-alpha)-converting enzyme] plays an essential role in the shedding of TNF-alpha, which could affect the outcome of AMI (acute myocardial infarction). To investigate the clinical significance of the TACE-TNF-alpha system in AMI, we examined TACE-mediated TNF-alpha synthesis in PBMCs (peripheral blood mononuclear cells), which are a possible source of TNF-alpha in AMI. Forty-one patients with AMI and 15 healthy subjects (HS) were enrolled in the present study. PBMCs were isolated from peripheral blood on day 1 and 14 after the onset of AMI. TACE and TNF-alpha mRNA levels and intracellular median fluorescence intensity were measured by real-time RT (reverse transcriptase)-PCR and flow cytometry respectively. TACE-mediated TNF-alpha production was evaluated in cultured PBMCs with PMA, which is known to activate TACE. Spontaneous TACE and TNF-alpha levels were higher in AMI patients than in HS (P<0.001). TACE and TNF-alpha levels in PMA-stimulated PMBCs were markedly increased in AMI patients compared with HS (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in AMI. Although spontaneous and stimulated levels of TACE and TNF-alpha decreased 14 days after the onset of AMI, levels in AMI patients were higher than in HS. In AMI patients with in-hospital complications (n=15; pump failure in ten, recurrent myocardial infarction in one, malignant ventricular arrhythmia in three and cardiac death in one), spontaneous and stimulated levels of TACE and TNF-alpha were higher than in patients without complications (P<0.01). These levels were higher in AMI patients with in-hospital complications 14 days after onset. These results demonstrate that TACE-mediated TNF-alpha maturation in PBMCs may play an important role in poor outcomes from AMI, suggesting that TACE may be a potential target for the inhibition of cellular TNF-alpha production in AMI.