Preview

Complex Issues of Cardiovascular Diseases

Advanced search

CYTOCHROME C IS A MITOCHONDRIAL DAMAGE MARKER: ASSOCIATIONS WITH CLINICAL PARAMETERS AND QUALITY OF LIFE OF HEART FAILURE PATIENTS WITH CORONARY ARTERY DISEASE

https://doi.org/10.17802/2306-1278-2025-14-4-18-27

Abstract

Highlights

  • The association of cytochrome C concentration, a marker of mitochondrial damage, with the left ventricular ejection fraction (LVEF), exercise tolerance and quality of life in heart failure (HF) patients with reduced and mildly reduced LVEF of ischemic etiology has been shown. The obtained results emphasize the importance of mitochondrial dysfunction in the pathogenesis of HF.

 

Abstract

Background. A feature of the pathogenesis of chronic heart failure (HF) in patients with coronary artery disease (CAD) is the development of myocardial dysfunction against the background of repeated episodes of ischemia/reperfusion. Damage to the mitochondria of cardiomyocytes leads to stimulation of cell death and the release of mitochondrial DNA and mitochondrial enzymes into the interstitium and blood. Cytochrome C is one of the mitochondrial proteins released into the systemic circulation, but the clinical significance of cytochrome C in HF remains poorly understood.

Aim. The aim of this study was to search for associations between cytochrome C concentration and clinical characteristics of HF of ischemic etiology, including quality of life, as well as to analyze the dynamics of cytochrome C in the postoperative period after coronary artery bypass grafting (CABG).

Methods. The study included 30 patients aged 67 (58; 71) years with HF with reduced (HFrEF) and mildly reduced (HFmrEF) left ventricular ejection fraction (LVEF), who were scheduled for CABG. All patients underwent collection of complaints, anamnesis, standard laboratory and instrumental dates. Quality of life was assessed using the Kansas Cardiomyopathy Questionnaire (KCCQ). Blood samples for determination of cytochrome C concentration were taken before CABG and on days 3 and 10 after surgery. Statistical processing of the results was performed using IBM SPSS 21.0.

Results. The cytochrome C concentration before CABG in the study cohort was 24.1 (17.1; 31.1) ng/ml. Patients were divided into two equal groups (n = 15) depending on the cytochrome C level: group 1 included patients with cytochrome C concentration less than or equal to the median value, group 2 – with cytochrome C concentration values ​​greater than the median. Patients in group 2 had lower values ​​of distance in the six-minute walk test: 341 (232; 370) m, compared with group 1 – 400 (310; 440) m (p = 0.048). Lower values ​​of quality of life were recorded in patients of group 2 (p = 0.046). The value of LVEF was also statistically significantly different in the analyzed groups: 44.5 (36.5; 48.3) % and 30 (28; 44) %, respectively, in groups 1 and 2 (p = 0.029). In addition, it was shown that in group 1, on the third day after CABG, a statistically significant increase in the concentration of cytochrome C was recorded (p = 0.05), while in group 2, no pronounced dynamics of this indicator in the perioperative period were revealed.

Conclusion. Elevated blood cytochrome C concentrations in patients with HFrEF and HFmrEF and coronary artery disease are associated with lower LVEF values, a shorter six-minute walk distance, and worse quality of life. Cytochrome C dynamics after CABG depended on the initial concentration of this marker.

About the Authors

Elena A. Kuzheleva
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

Candidate of Medical Sciences, Researcher, Department of Myocardial Pathology, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



Alla A. Garganeeva
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

Doctor of Medical Sciences, Professor, Head of the Department of Myocardial Pathology, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



Olga V. Tukish
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

Candidate of Medical Sciences, Researcher, Department of Myocardial Pathology, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



Ekaterina E. Syromyatnikova
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

Resident, Department of Myocardial Pathology, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



Beligma B. Dorzhieva
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

Resident, Department of Myocardial Pathology, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



Oksana N. Ogurkova
Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”
Russian Federation

PhD, researcher, Department of Clinical Laboratory Diagnostics, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation



References

1. Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023 Jan 18;118(17):3272-3287. doi: 10.1093/cvr/cvac013. Erratum in: Cardiovasc Res. 2023 Jun 13;119(6):1453. doi: 10.1093/cvr/cvad026.

2. Shlyakhto E. V., Belenkov Yu. N., Boytsov S. A., Villevalde S. V., Galyavich A. S., Glezer M. G., et ak. Interim analysis of a prospective observational multicenter registry study of patients with chronic heart failure in the Russian Federation "PRIORITET-CHF": initial characteristics and treatment of the first included patients. Russian Journal of Cardiology. 2023;28(10):5593. doi:10.15829/1560-4071-2023-5593

3. Canepa M, Anastasia G, Ameri P, Vergallo R, O'Connor CM, Sinagra G, Porto I. Characterization of ischemic etiology in heart failure with reduced ejection fraction randomized clinical trials: A systematic review and meta-analysis. Eur J Intern Med. 2025 Feb 11:S0953-6205(25)00042-1. doi: 10.1016/j.ejim.2025.02.004. Epub ahead of print. PMID: 39939263.

4. Panza JA, Ellis AM, Al-Khalidi HR, et al. Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy. N Engl J Med. 2019 Aug 22;381(8):739-748. doi: 10.1056/NEJMoa1807365

5. Heusch G. Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease. Med. 2024 Jan 12;5(1):10-31. doi: 10.1016/j.medj.2023.12.007. PMID: 38218174.

6. Khoynezhad A, Jalali Z, Tortolani AJ. Apoptosis: pathophysiology and therapeutic implications for the cardiac surgeon. Ann Thorac Surg. 2004 Sep;78(3):1109-18. doi: 10.1016/j.athoracsur.2003.06.034. PMID: 15337071.

7. Cocchi MN, Salciccioli J, Yankama T, Chase M, Patel PV, Liu X, et al. Predicting Outcome After Out-of-Hospital Cardiac Arrest: Lactate, Need for Vasopressors, and Cytochrome c. J Intensive Care Med. 2020 Dec;35(12):1483-1489. doi: 10.1177/0885066619873315. Epub 2019 Aug 29. PMID: 31466497.

8. Andersen LW, Liu X, Montissol S, Holmberg MJ, Fabian-Jessing BK, Donnino MW; Center for Resuscitation Science Research Group. Cytochrome c in patients undergoing coronary artery bypass grafting: A post hoc analysis of a randomized trial. J Crit Care. 2017 Dec;42:248-254. doi: 10.1016/j.jcrc.2017.08.006.

9. Garganeeva A.A., Kuzheleva E.A., Tukish O.V., Vitt K.N., Andreev S.L., Muslimova E.F., Korepanov V.A., Afanasiev S.A., Gulya M.O., Syromyatnikova E.E., Vladimirova E.A., Stepanov I.V. Possibilities of diagnosis of mitochondrial dysfunction in chronic heart failure. Siberian Journal of Clinical and Experimental Medicine. 2024;39(3):51–57. https://doi.org/10.29001/2073-8552- 2024-39-3-51-57

10. Alves-Figueiredo H, Silva-Platas C, Lozano O, Vázquez-Garza E, Guerrero-Beltrán CE, Zarain-Herzberg A, García-Rivas G. « A systematic review of post-translational modifications in the mitochondrial permeability transition pore complex associated with cardiac diseases. Biochim Biophys Acta Mol Basis Dis. 2021 Jan 1;1867(1):165992. doi: 10.1016/j.bbadis.2020.165992

11. Paraskevaidis I, Kourek C, Farmakis D, Tsougos E., «Mitochondrial Dysfunction in Cardiac Disease: The Fort Fell. Biomolecules. 2024 Nov 29;14(12):1534. doi: 10.3390/biom14121534. PMID: 39766241; PMCID: PMC11673776.

12. Galyavich A. S., Tereshchenko S. N., Uskach T. M., Ageev F. T., Aronov D. M., Arutyunov G. P., et al. 2024 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2024;29(11):6162. doi: 10.15829/1560-4071-2024-6162.

13. Goedeke L, Ma Y, Gaspar RC, Nasiri A, Lee J, Zhang D, Galsgaard KD, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard BT, Haedersdal S, Wu X, Stack J, Dufour S, Butrico GM, Kahn M, Perry RJ, Cline GW, Young LH, Shulman GI. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. J Clin Invest. 2024 Dec 16;134(24):e176708. doi: 10.1172/JCI176708.

14. Shu H, Hang W, Peng Y, Nie J, Wu L, Zhang W, Wang DW, Zhou N. Trimetazidine Attenuates Heart Failure by Improving Myocardial Metabolism via AMPK. Front Pharmacol. 2021 Sep 15;12:707399. doi: 10.3389/fphar.2021.707399. PMID: 34603021; PMCID: PMC8479198.

15. Shah YR, Turgeon RD. Impact of SGLT2 Inhibitors on Quality of Life in Heart Failure Across the Ejection Fraction Spectrum: Systematic Review and Meta-analysis. CJC Open. 2023 Dec 10;6(4):639-648. doi: 10.1016/j.cjco.2023.12.002.

16. Nassiri S, Van de Bovenkamp AA, Remmelzwaal S, Sorea O, de Man F, Handoko ML. Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis. Open Heart. 2024 May 8;11(1):e002579. doi: 10.1136/openhrt-2023-002579. PMID: 38719498; PMCID: PMC11086535.


Supplementary files

Review

For citations:


Kuzheleva E.A., Garganeeva A.A., Tukish O.V., Syromyatnikova E.E., Dorzhieva B.B., Ogurkova O.N. CYTOCHROME C IS A MITOCHONDRIAL DAMAGE MARKER: ASSOCIATIONS WITH CLINICAL PARAMETERS AND QUALITY OF LIFE OF HEART FAILURE PATIENTS WITH CORONARY ARTERY DISEASE. Complex Issues of Cardiovascular Diseases. 2025;14(4):18-27. (In Russ.) https://doi.org/10.17802/2306-1278-2025-14-4-18-27

Views: 19


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2306-1278 (Print)
ISSN 2587-9537 (Online)