Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy

The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocard ium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiompopathy. Left ventricular en zyme activities, mRNA and protein levels of the hydrogen peroxide scavengin g enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxi de anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD ) superoxide dismutases were measured, In failing myocardium, there was a s ignificant decrease in CAT activity (4.83 +/- 0.32 U/mg v 6.59 +/- 0.52, P< 0.01) despite unchanged mRNA expression and protein levels, GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As in direct free radical markers, similar levels of the products of lipid peroxi dation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyr osin content were measured, The decrease in CAT activity appears to be a po st-transcriptional mechanism. A decreased myocardial capacity to scavenge h ydrogen peroxide might lead to a shift in the intracellular redox balance w hich potentially results in activation of redox sensitive signalling pathwa ys, Direct reactive oxygen species mediated damage was not detected by the methods applied. (C) 2000 Academic Press.