Increased mRNA expression of tumour necrosis factor-alpha and its converting enzyme in circulating leucocytes of patients with acute myocardial infarction.

Abstract

Tumour necrosis factor-alpha (TNF-alpha) plays an important role in myocardial damage in acute myocardial infarction (AMI). It has recently been discovered that TNF-alpha-converting enzyme (TACE) cleaves precursor TNF-alpha into its mature form. However, it remains unknown whether TNF-alpha expression is related to TACE expression in circulating leucocytes in AMI. Blood samples were obtained from 37 patients with AMI within 24 h of onset and eight healthy controls. Plasma TNF-alpha levels were measured by ELISA. Total mRNA was then extracted from circulating leucocytes, and the expression levels of TACE and TNF-alpha mRNAs were determined by reverse transcriptase-PCR. Plasma TNF-alpha levels were significantly higher in patients with Killip's classes III and IV AMIs (17.1+/-5.0 pg/ml, n =11) than in those with Killip's classes I and II AMIs (13.7+/-4.2 pg/ml, n =26), or controls (13.0+/-1.7 pg/ml, n =8) ( P <0.05). There was a significant increase in expression (arbitrary units) of TACE and TNF-alpha mRNAs in circulating leucocytes obtained from patients with Killip's classes I and II AMIs [TACE/glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 2.770+/-0.303; TNF-alpha/GAPDH, 2.123+/-0.475] compared with controls (TACE/GAPDH, 1.498+/-0.209; TNF-alpha/GAPDH, 1.283+/-0.274) ( P <0.01). This increase was even greater in patients with Killip's classes III and IV AMIs (TACE/GAPDH, 3.086+/-0.354; TNF-alpha/GAPDH, 2.808+/-0.422) ( P <0.01). Moreover, there was a significant positive relationship between these mRNA expression levels ( r =0.60, P <0.01). The TACE-TNF-alpha system in circulating leucocytes is stimulated and may have a negative impact on clinical outcome in AMI.