Functional ability of mitochondria and mitochondrial genome polymorphism as factors affecting arrhythmogenesis in chronic coronary artery disease

Abstract

Aim. To investigate functional state of mitochondria and mitochondrial DNA (mtDNA) polymorphism in coronary artery disease (CAD) patients with life-threatening cardiac rhythm disorders (CRD).Methods. We investigated venous blood samples of 45 patients with uncomplicated CAD and 120 CAD patients with CRD. Oxygen consumption rate of mitochondrias of leukocytes in V3 and V4 states were determined in pyruvate-malate and succinate buffers, as well as in the presence of palmitic acid (PA). In patients with complicated CAD, mtDNA haplogroup and substitutions in gene encoding proteins of the respiratory chain complexes and mitochondrial rRNA were determined. Statistical analysis was performed using Mann-Whitney, Wilcoxon tests and Chi-square test with Yates’ correction.Results. In CAD and CAD with CRD, oxygen consumption rate of intact mitochondria did not different in either pyruvate-malate or succinate buffers. In uncomplicated CAD, PA supplementation increases oxygen consumption rate by mitochondria in both succinate and pyruvate-malate buffers. The majority of patients (41%) with CAD and CRD were carriers of the haplogroup «H» and, in this indicator, the sample did not differ from patients with uncomplicated CAD. However, mtDNA of patients with complicated CAD was characterized by a more frequent combined carriage of two and more missense substitutions in genes of respiratory chain and rRNA.Conclusion. Mitochondria of patients with coronary artery disease and life-threatening cardiac rhythm disorders have reduced functional reserve. The distribution of frequencies of main mtDNA haplogroups of patients with coronary artery disease with life threatening cardiac rhythm disorders corresponds to the population. The mtDNA of such patients is characterized by a high frequency of carriage of combined polymorphisms in gene of electron transport chain proteins and rRNA.