Age-related aspects of the sirtuin expression level in the cardiomyocytes of patients with dilated cardiomyopathy

DOI: https://doi.org/10.29296/25877305-2022-10-14
Issue: 
10
Year: 
2022

K. Kravchenko(1); Professor K. Kozlov(1, 2), MD; Professor V. Polyakova(3, 4), Biol.D; Professor D. Medvedev(1, 5), MD
1-Saint Petersburg Institute of Bioregulation and Gerontology
2-S.M. Kirov Military Medical Academy, Saint Petersburg
3-Saint Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of Russia
4-Belgorod State National Research University,
5-Research Institute of Hygiene, Occupational Diseases, and Human Ecology, Federal Biomedical Agency of Russia, Saint Petersburg

Sirtuins are among the signaling molecules that may have important prognostic value in dilated cardiomyopathy (DCM). Objective. To study the expression level of sirtuins in the cardiomyocytes of patients with DCM in vitro. Subjects and methods. The study used cardiomyocyte cultures taken during heart biopsy from 3 middle-aged male patients (mean age 52.3±2.6 years) with DCM. A culture of normal human cardiomyocytes served as a control. The investigators applied a primary dissociated cell culturing method and immunofluorescence confocal laser scanning microscopy. To simulate cellular senescence, they employed Passages 3 and 10 cells that corresponded to young and old cultures. Results. At the molecular level, cardiomyocyte aging was accompanied by a decrease in the expression of sirtuins 1, 3, and 6; whereas the expression of sirtuin 2 increased significantly in the old cultures versus the young ones in both the control and DCM groups. The findings suggest may suggest that sirtuins 1, 2, 3, and 6 are involved not only in the pathogenesis of DCM, but also in the mechanisms of aging.

Keywords: 
dilated cardiomyopathy
cardiac cell aging
sirtuins
cell culture
confocal microscopy



References: 
  1. Anderson R., Lagnado A., Maggiorani D. et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 2019; 38 (5): e100492. DOI: 10.15252/embj.2018100492
  2. Anderson R., Richardson G.D., Passos J.F. Mechanisms driving the ageing heart. Exp Gerontol. 2018; 109: 5–15. DOI: 10.1016/j.exger.2017.10.015
  3. Bykov A.T., Dyuzhikov A.A., Malyarenko T.N. Current views on age-related and dependent cardiovascular diseases. Medical Journal. 2015; 3: 7–12.
  4. Cardus A., Uryga A.K., Walters G. et al. SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res. 2013; 97: 571–9. DOI: 10.1093/cvr/cvs352
  5. Elliott P., Andersson B., Arbustini E. et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008; 29: 270–6. DOI: 10.1093/eurheartj/ehm342
  6. Frescas D., Valenti L., Accili D. Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem. 2005; 280 (21): 20589–95. DOI: 10.1074/jbc.M412357200
  7. Gerhart-Hines Z., Rodgers J.T., Bare O. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007; 26 (7): 1913–23. DOI: 10.1038/sj.emboj.7601633
  8. Guzzo-Merello G., Cobo-Marcos M., Gallego-Delgado M. et al. Alcoholic cardiomyopathy. World J Cardiol. 2014; 6 (8): 771–81. DOI: 10.4330/wjc.v6.i8.771
  9. Houtkooper R.H., Pirinen E., Auwerx J. Sirtuins as regu lators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012; 13 (4): 225–38. DOI: 10.1038/nrm3293
  10. Japp A.G., Gulati A., Cook S.A. et al. The Diagnosis and Evaluation of Dilated Cardiomyopathy. J Am Coll Cardiol. 2016; 67 (25): 2996–3010. DOI: 10.1016/j.jacc.2016.03.590
  11. Kanfi Y., Naiman S., Amir G. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012; 483 (7388): 218–21. DOI: 10.1038/nature10815
  12. Kitamura Y.I., Kitamura T., Kruse J.P. FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab. 2005; 2 (3): 153–63. DOI: 10.1016/j.cmet.2005.08.004
  13. Lagouge M., Argmann C., Gerhart-Hines Z. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006; 127 (6): 1109–22. DOI: 10.1016/j.cell.2006.11.013
  14. Liu J., Wu X., Wang X. et al. Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress. Int J Mol Sci. 2013; 14: 5633–49. DOI: 10.3390/ijms14035633
  15. Lopez-Otin C., Blasco M.A., Partridge L. et al. The hallmarks of aging. Cell. 2013; 153 (6): 1194–217. DOI: 10.1016/j.cell.2013.05.039
  16. McNally E.M., Mestroni L. Dilated Cardiomyopathy: Genetic Determinants and Mechanisms. Circ Res. 2017; 121 (7): 731–48. DOI: 10.1161/CIRCRESAHA.116.309396
  17. Merlo M., Cannatà A., Gobbo M. et al. Evolving concepts in dilated cardiomyopathy. Eur J Heart Fail. 2018; 20 (2): 228–39. DOI: 10.1002/ejhf.1103
  18. Michan S., Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007; 404 (1): 1–13. DOI: 10.1042/BJ20070140
  19. Moynihan K.A., Grimm A.A., Plueger M.M. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005; 2 (2): 105–17. DOI: 10.1016/j.cmet.2005.07.001
  20. Narayan N., Lee I.H., Borenstein R. et al. The NAD-dependent deacetylase SIRT2 is required for programmed necrosis. Nature. 2012; 492: 199–204. DOI: 10.1038/nature11700
  21. North B.J., Rosenberg M.A., Jeganathan K.B. et al. SIRT2 induces the checkpoint kinase BubR1 to increase lifes-pan. EMBO J. 2014; 33: 1438–53. DOI: 10.15252/embj.201386907
  22. O’Callaghan C., Vassilopoulos A. Sirtuins at the crossroads of stemness, aging, and cancer. Aging Cell. 2017; 16 (6): 1208–18. DOI: 10.1111/acel.12685
  23. Parodi-Rullán R.M., Chapa-Dubocq X.R., Javadov S. Acetylation of Mitochondrial Proteins in the Heart: The Role of SIRT3. Front Physiol. 2018; 9: 1094. DOI: 10.3389/fphys.2018.01094
  24. Picard F., Kurtev M., Chung N. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004; 429 (6993): 771–6. DOI: 10.1038/nature02583
  25. Pinto Y.M., Elliott P.M., Arbustini E. et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2016; 37: 1850–8. DOI: 10.1093/eurheartj/ehv727
  26. Prozorovski T., Schulze-Topphoff U., Glumm R. Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol. 2008; 10 (4): 385–94. DOI: 10.1038/ncb1700
  27. Rodgers J.T., Lerin C., Haas W. et al. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434 (7029): 113–8. DOI: 10.1038/nature03354
  28. Schultheiss H.P., Fairweather D., Caforio A.L.P. et al. Dilated cardiomyopathy. Nat Rev Dis Primers. 2019; 9 (5): 32. DOI: 10.1038/s41572-019-0084-1
  29. Shimizu I., Minamino T. Cellular senescence in cardiac diseases. J Cardiol. 2019; 74 (4): 313–9. DOI: 10.1016/j.jjcc.2019.05.002
  30. Sun C., Zhang F., Ge X. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007; 6 (4): 307–19. DOI: 10.1016/j.cmet.2007.08.014
  31. Weintraub R.G., Semsarian C., Macdonald P. Dilated cardiomyopathy. Lancet. 2017; 390 (10092): 400–14. DOI: 10.1016/S0140-6736(16)31713-5
  32. Xu Z., Zhang L., Fei X. et al. The miR-29b-Sirt1 axis regulates self-renewal of mouse embryonic stem cells in response to reactive oxygen species. Cell Signal. 2014; 26: 1500–5. DOI: 10.1016/j.cellsig.2014.03.010
  33. Zhang, J., He Z., Fedorova J. Alterations in mitochondrial dynamics with age-related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility. Aging Cell. 2021; 20 (7): e13419. DOI: 10.1111/acel.13419
  34. Дедов Д.В. Комплексная профилактика возраст-ассоциированных и сердечно-сосудистых заболеваний: применение российского натурального препарата БиоДигидрокверцетин торговой марки «Байкальская Легенда». Врач. 2022; 33 (6): 64–7 [Dedov D. Comprehensive prevention of age-related and cardiovascular diseases: the use of the Russian natural remedy BioDihydroquercetin of the Baikal Legend trade mark. Vrach. 2022; 33 (6): 64–7 (in Russ.)]. DOI: 10.29296/25877305-2022-06-11
  35. Обрезан А.Г., Куликов Н.В. Желудочковые экстрасистолии как причина кардиомиопатий. Медицинский альянс. 2018; 4: 70–5 [Obrezan A., Kulikov N. Ventricular extrasystoles as the cause of cardiomyopathy. Meditsinskii al'yans. 2018; 4: 70–5 (in Russ.)].