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

S. A. Afanasiev, V. A. Korepanov, N. P. Babushkina, T. Rebrova, E. Muslimova, M. Golubenko, A. A. Garganeeva, T. Atabekov
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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.
线粒体的功能能力和线粒体基因组多态性是影响慢性冠心病心律失常发生的因素
目的研究威胁生命的心律失常(CRD)的冠状动脉疾病(CAD)患者的线粒体功能状态和线粒体 DNA(mtDNA)多态性。我们调查了 45 名无并发症的 CAD 患者和 120 名患有 CRD 的 CAD 患者的静脉血样本。在丙酮酸-苹果酸和琥珀酸缓冲液中,以及在棕榈酸(PA)存在的情况下,测定了 V3 和 V4 状态下白细胞线粒体的耗氧量。在复杂性 CAD 患者中,测定了 mtDNA 单倍群和呼吸链复合体蛋白编码基因及线粒体 rRNA 的替换。统计分析采用 Mann-Whitney 检验、Wilcoxon 检验和带有 Yates 校正的 Chi-square 检验。在 CAD 和有 CRD 的 CAD 中,完整线粒体的耗氧率在丙酮酸-苹果酸或琥珀酸缓冲液中没有差异。在无并发症的 CAD 患者中,补充 PA 可提高线粒体在琥珀酸和丙酮酸-苹果酸缓冲液中的耗氧量。大多数(41%)患有 CAD 和 CRD 的患者是单倍群 "H "的携带者,在这一指标上,样本与未并发 CAD 的患者没有差异。然而,并发 CAD 患者的 mtDNA 的特点是呼吸链和 rRNA 基因中更频繁地合并携带两个或更多的错义置换。冠心病和危及生命的心律失常患者的线粒体功能储备降低。冠心病合并危及生命的心律失常患者的主要 mtDNA 单倍群频率分布与人群相符。这类患者的 mtDNA 的特点是电子传递链蛋白和 rRNA 基因的组合多态性携带频率较高。
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