HAC (Russian)
RSCI (Russian)
EBSCO
DOI (USA)
Ulrichsweb (Ulrich’s Periodicals Directory)
Scientific Indexing Services

Age-related features of melatonin receptor expression in the cardiomyocytes of patients with dilated cardiomyopathy

DOI: https://doi.org/10.29296/25877305-2021-09-14
Issue: 
9
Year: 
2021

K. Kravchenko(1); K. Kozlov(1); D. Medvedev(1, 2); Professor V. Polyakova(3, 4), Biol.D;
Professor of the Russian Academy of Sciences; E. Malyutina(4); E. Borisova(5), MD (1)Saint Petersburg
Institute of Bioregulation and Gerontology (2)Research Institute of Hygiene, Occupational Diseases, and
Human Ecology, Federal Biomedical Agency of Russia, Saint Petersburg (3)Saint Petersburg State Pediatric
Medical University, Ministry of Health of Russia (4)Belgorod State National Research University (5)M.F.
Vladimirsky Moscow Regional Research Clinical Institute, Moscow

To understand the pathogenesis of dilated cardiomyopathy (DCM), it is necessary to establish the molecular and cellular mechanisms of myocardial aging, including those associated with melatonin. The latter affects vascular tone, the binding of smooth muscle cells and vascular endothelium to their own receptors (melatonin receptor type 1A (MR1A), melatonin receptor 1B (MR1B)) and acts on the adrenergic and peptidergic (vasointestinal peptide and substance P) endings of perivascular nerves, which allows melatonin to be considered as an important predictor of the development of DCM. The molecular mechanisms of this interaction still remain insufficiently studied. Objective: to study MR1A and MR1V in the cardiomyocytes of patients with DCM in vitro. Methods. Primary dissociated cell cultures and immunofluorescence confocal laser scanning microscopy were used. Passages 3 and 10 cells corresponding to young and old cultures were applied to model cellular senescence. Results. At the molecular level, cardiomyocyte senescence was accompanied by a 3-fold decrease in the level of MR1B expression compared to the old cultures in both the control and the DCM groups (by 1.8 times). Furthermore, there was a 2-fold decrease in MR1A expression in the cell cultures taken from patients with DCM compared with the similar culture of normal cardiomyocytes. The expression of MR1B was significantly lower in the DCM group than that in the control group in passage 3. With aging in the cultures, the level of MR1B expression was significantly lower by 3.9 times in the DCMP group than that in the control group. The similar trends in the studied markers may suggest that both melatonin receptors are involved in the pathogenesis of DCM, which may also be involved in the mechanisms of aging. The findings will be able to expand the concept of DCM and to form its diagnostic panel in people of different ages.

Keywords: 
geriatrics
cardiology
dilated cardiomyopathy
heart cellular senescence
melatonin receptors
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. Shimizu I., Minamino T. Cellular senescence in cardiac diseases. J Cardiol. 2019; 74 (4): 313–9. DOI: 10.1016/j.jjcc.2019.05.002
  3. McNally E.M., Mestroni L. Dilated Cardiomyopathy: Genetic Determinants and Mechanisms. Circ Res. 2017; 121 (7): 731–48. DOI: 10.1161/CIRCRESAHA.116.309396
  4. 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
  5. 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
  6. 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
  7. 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
  8. Weintraub R.G., Semsarian C., Macdonald P. Dilated cardiomyopathy. Lancet. 2017; 390 (10092): 400–14. DOI: 10.1016/S0140-6736(16)31713-5
  9. 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 (2): 270–6. DOI: 10.1093/eurheartj/ehm342
  10. 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
  11. 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
  12. 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
  13. Kurganova Ju.M., Danilov A.B., Gorjachev D.V. Melatonin i bol'. Zhurnal nevrologii i psihiatrii im. SS. Korsakova. 2014; 114 (6): 31–7 [Kurganova Iu.M., Danilov A.B., Goriachev D.V. Melatonin and pain. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014; 114 (6): 31–7 (in Russ.)].
  14. 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
  15. Rapoport S.I., Golichenkov V.A. Melatonin: teorija i praktika. M.: Medpraktika-M, 2009; 100 s. [Rapoport S.I., Golichenkov V.A. Melatonin: teoriya i praktika. M.: Medpraktika-M, 2009; 100 p. (in Russ.)].
  16. Arendt J., Bojkowski C., Folkard S. et al. Some effects of melatonin and the control of its secretion in humans. Ciba Found Symp. 1985; 117: 266–83. DOI: 10.1002/9780470720981.ch16
  17. Arendt J. Melatonin in humans: it’s about time. J Neuroendocrinol. 2005; 17 (8): 537–8. DOI: 10.1111/j.1365-2826.2005.01333.x
  18. Vajhanskaja T.G., Sivitskaja L.N., Kurushko T.V. i dr. Dilatatsionnaja kardiomiopatija: novyj vzgljad na problemu. Rossijskij kardiologicheskij zhurnal. 2019; 4: 35–47 [Vaykhanskaya T.G., Sivitskaya L.N., Kurushko T.V. et al. Dilated cardiomyopathy: reconceptualization of the problem. Russian Journal of Cardiology. 2019; 4: 35–47 (in Russ.)]. DOI: 10.15829/1560-4071-2019-4-35-47