Clin Res Cardiol 96:Suppl 2 (2007)

P342 - Disbalance of cytochrome c oxidase - subunit composition in pathogenesis of dilated cardiomyopathy
V. Ruppert1, S. Pankuweit1, R. Moosdorf2, B. Maisch1, S. Vogt2
1Klinik für Innere Medizin - Schwerpunkt Kardiologie, Universitätsklinikum Giessen und Marburg, Marburg; 2Klinik für Herz- und thorakale Gefäßchirurgie, Universitätsklinikum Giessen und Marburg, Marburg;
The cytochrome c oxidase (CcO) is known as complex IV of the respiratory chain. It is suspected to be the terminal and determinating enzyme system for electron transfer and mitochondrial membrane potential sustenance essential for ATP- production. The enzyme has 3 structural mitochondrial encoded and 10 regulative nuclear encoded subunits which can be  phosphorylated, occasionally, in case of ischemic myocardium. The phosphorylation status of the CcO- subunits  is suspected to regulate second step of respiratory control.
Because of these pivotal items the dysfunction of CcO- subunit interaction should be investigated for its role in pathogenesis of dilated cardiomyopathy.
In this study we examined both, the mRNA expression of mitochondrial encoded subunit II and nuclear encoded subunit IV of cytochrome c oxidase (CcO) of patients with DCM compared with controls.
Total RNA was extracted from myocardial biopsies (EMB) of patients with a reduced LV ejection fraction (EF) < 0.45 and/or a left ventricular end diastolic dimension (LVEDD) of > 112% of the predicted value were classified as having nonischemic DCM. Real-time PCR analysis was performed with specific primers for subunits II and IV of CcO followed by a melt curve analysis.
Gene expression analysis in EMB of DCM patients assessed by real-time PCR showed a significant decrease of CcO IV mRNA (p < 0.001 vs. controls) but no significant differences in CcO II. Correlations between CcO IV mRNA expression and EF (r=0.543, p<0.001) as well as  LVEDD (r=-0.418 (p<0.01) could be detected.
The decreased mRNA expression may result in reduced Cytochrome c oxidase activity and compromised mitochondrial function. We hypothesize a downregulation of nuclear- encoded regulatory CcO- subunits in nonischemic DCM and subsequent mitochondrial dysfunction. The imbalance of CcO- subunit- downregulation might lead to radical oxygen production and inadequate maintainance of  ATP levels. This dysregulation is likely to contribute in the pathophysiology of the disease.