COMPARATIVE ANALYSIS OF MITOCHONDRIAL DNA COPY NUMBERS IN MYOCARDIAL TISSUE IN SUDDEN CARDIAC AND NON-CARDIAC DEATH

The aim of the work is to compare the number of copies of mtDNA in myocardial tissue in persons who died of sudden cardiac and non-cardiac death.

Material and methods. Group of sudden cardiac death (SCD, 150 samples): the autopsy material was collected from those who suddenly died outside the medical and preventive treatment facilities of persons who underwent a forensic medical examination according to a standard protocol. As a control group (n = 150), a sample of individuals (selected by gender and age) was used, which, according to the conclusion of the forensic medical examination, died suddenly from other causes (SD). The study of the number of copies of mtDNA was performed in DNA samples isolated from myocardial tissue by the method of phenol-chloroform extraction, using real-time quantitative PCR (qPCR).

Results. In both studied groups, there are no significant correlations of the number of copies of mtDNA with age in both men and women. In the general regression analysis, with the introduction of age into the model, the difference between the SCD and SD groups was obtained in the number of copies of mtDNA (p = 0.01). When divided by sex in the group of women, there are no differences between SCD and SD in the number of copies of mtDNA (p = 0.089). In men, differences in the number of copies of mtDNA persist between SCD and SD (p = 0.023). High variability in the number of copies of mtDNA in the myocardium was noted even within the same group in individuals of the same sex and of comparable age compared to the variability in the number of copies of mtDNA in peripheral blood leukocytes (according to the literature). This is probably due to the heterogeneity of the groups on the etiology and pathogenesis of sudden death. In men, the decrease in the number of copies of mtDNA in the group with SCD, compared with those who died suddenly from other causes, is more pronounced at the age of 50 years and older.

Conclusion. The number of copies of mtDNA in myocardial tissue in men who have died of SCD is lower, compared with men who died suddenly from other causes (especially over the age of 50 years).

1. Priori S.G., Blomström-Lundqvist C., Mazzanti A., Blom N., Borggrefe M., Camm J., Elliott P.M., Fitzsimons D., Hatala R., Hindricks G., Kirchhof P., Kjeldsen K., Kuck K.H., Hernandez-Madrid A., Nikolaou N., Norekvål T.M., Spaulding C., van Veldhuisen D.J. The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology // G. Ital. Cardiol. (Rome). 2016. Vol. 17, N 2. P. 108–170.

2. Шляхто Е.В., Арутюнов Г.П., Беленков Ю.Н., Ардашев А.В. Национальные рекомендации по определению риска и профилактике внезапной сердечной смерти // Арх. внутр. медицины. 2013. ¹ 4. С. 5–15.

3. Winkel B.G., Jabbari R., Tfelt-Hansen J. How to prevent SCD in the young? // Int. J. Cardiol. 2017. Vol. 237. P. 6–9.

4. Faragli A., Underwood K., Priori S.G., Mazzanti A. Is there a role for genetics in the prevention of sudden cardiac death // J. Cardiovasc. Electrophysiol. 2016. Vol. 27, N 9. P. 1124–1132.

5. Максимов В.Н., Гуражева А.А., Максимова Ю.В. Количество копий митохондриальной ДНК лейкоцитов как маркёр предрасположенности к ИБС и ВСС // Атеросклероз. 2018. Т. 14, ¹ 3. С. 64–69.

6. Максимов В.Н., Малютина С.К., Орлов П.С., Иванощук Д.Е., Михайлова С.В., Шапкина М.Ю., Hubacek J., Holmes M., Bobak М., Воевода М.И. Число копий митохондриальной ДНК лейкоцитов как маркер старения и риска развития возраст-зависимых заболеваний у человека // Успехи геронтологии. 2019. Т. 32, ¹ 3. С. 422–430.

7. Chen S., Xie X., Wang Y., Gao Y., Xie X., Yang J., Ye J. Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: a case-control study // Atherosclerosis. 2014. Vol. 237, N 1. P. 220–226.

8. Latorre-Pellicer A., Moreno-Loshuertos R., Lechuga- Vieco A.V., Sánchez-Cabo F., Torroja C., Acín-Pérez R., Calvo E., Aix E., González-Guerra A., Logan A., Bernad-Miana M.L., Romanos E., Cruz R., Cogliati S., Sobrino B., Carracedo Á., Pérez-Martos A., Fernández-Silva P., Ruíz-Cabello J., Murphy M.P., Flores I., Vázquez J., Enríquez J.A. Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing // Nature. 2016. Vol. 535. P. 561–565.

9. Зиновкин Р.А., Скулачев М.В., Скулачев В.П. Ми- тохондриальный геном и продолжительность жизни (мини-обзор) // Биохимия. 2016. Т. 81, ¹ 12. С. 1669–1674.

10. Воропаев Е.В., Зятьков А.А., Осипкина О.В., Баранов О.Ю., Галиновская Н.В., Доценко В.Н. Метод молекулярно-генетической диагностики процессов клеточной сенесценции на основе количественного анализа генов ядерной и митохондриальной ДНК // Пробл. здоровья и экологии. 2016. ¹ 1. С. 46–50.

11. Ashar F.N., Zhang Y., Longchamps R.J., Lane J., Moes A., Grove M.L., Mychaleckyj J.C., Taylor K.D., Coresh J., Rotter J.I., Boerwinkle E., Pankratz N., Guallar E., Arking D.E. Association of mitochondrial DNA copy number with cardiovascular disease // JAMA Cardiol. 2017. Vol. 2, N 11. P. 1247–1255.

12. Huang J., Tan L., Shen R., Zhang L., Zuo H., Wang D.W. Decreased peripheral mitochondrial DNA copy number is associated with the risk of heart failure and long-term outcomes // Medicine (Baltimore). 2016. Vol. 95, N 15. ID e3323.

13. Zhang Y., Guallar E., Ashar F.N., Longchamps R.J., Castellani C.A., Lane J., Grove M.L., Coresh J., Sotoodehnia N., Ilkhanoff L., Boerwinkle E., Pankratz N., Arking D.E. Association between mitochondrial DNA copy number and sudden cardiac death: findings from the Atherosclerosis Risk in Communities study (ARIC) // Eur. Heart J. 2017. Vol. 38, N 46. P. 3443–3448.

14. Ashar F.N., Moes A., Moore A.Z., Grove M.L., Chaves P.H.M., Coresh J., Newman A.B., Matteini A.M., Bandeen-Roche K., Boerwinkle E., Walston J.D., Arking D.E. Association of mitochondrial DNA levels with frailty and all-cause mortality // J. Mol. Med. (Berl.). 2015. Vol. 93, N 2. P. 177–186.

15. Ajaz S., Czajka A., Malik A. Accurate measurement of circulating mitochondrial DNA content from human blood samples using real-time quantitative PCR // Methods Molec. Biol. 2015. Vol. 1264. P. 117–131.

16. Venegas V., Halberg M.C. Measurement of mitochondrial DNA copy number // Methods Molec. Biol. 2012. Vol. 837. P. 327–335.

17. Liu L.P., Cheng K., Ning M.A., Li H.H., Wang H.C., Li F., Chen S.Y., Qu F.L., Guo W.Y. Association between peripheral blood cells mitochondrial DNA content and severity of coronary heart disease // Atherosclerosis. 2017. Vol. 261. P. 105–110.