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Aim. To study content of resident progenitor cardiomyocytes in endomyocardial biopsy samples of patients with dilated cardiomyopathy (DCM) and heart failure (HF) at different disease stages and relate it to patient clinical characteristics.

Material and methods. Resident progenitor cardiomyocytes were studied in endomyocardial biopsy samples from 14 patients (age from 26 to 52 years old) with DCM and HF by immunofluorescence method. Results were analyzed individually for each patient.

Results. Resident progenitor cardiomyocytes expressing simultaneously stem cell markers c-kit, MDR-1 and early cardiomyocyte differentiation markers GATA-4 and Nkx2.5 were found in endomyocardial biopsy samples from patients with DCM and HF. Resident progenitor cardiomyocytes detected by these cell markers were found in all patients at all disease stages.

Conclusion. Results show that the myocardial regenerative processes exist at all stages of the disease progression.

About the Authors

T. G. Kulikova
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

O. V. Stepanova
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

M. P. Valihov
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

A. Yu. Shhedrina
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

A. N. Samko
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

V. P. Masenko
Russian Cardiology Research and Production Complex, Moscow
Russian Federation

S. N. Tereshhenko
Russian Cardiology Research and Production Complex, Moscow
Russian Federation


1. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002;347:1397-402.

2. Stewart S, MacIntyre K, Hole DJ, et al. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001;3:315-22.

3. CihakovaD., Rose N.R. Pathogenesis of myocarditis and dilated cardiomyopathy.Adv Immunol 2008;99:9.

4. Dhalla NS, Saini-Chohan HK, Rodriguez-Leyva D, et al. Subcellular remodeling may induce cardiac dysfunction in congestive heart failure. Cardiovasc Res 2009; 81:429-38.

5. Distefano G, Siacca P. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure. Italian Journal of Pediatrics 2012; 38:41

6. Kuwahara K, Nakao K. New molecular mechanisms for cardiovascular disease: transcriptional pathways and novel therapeutic targets in heart failure. J Pharmacol Sci 2011; 116:337-42

7. Diwan A, Dorn GW II. Decompensation of cardiac hypertrophy: cellular mechanisms and novel therapeutic targets. Physiology 2007; 22:56-64

8. Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol 2010; 72: 19-44.

9. Bergmann O, Zdunek S, Alkass K, et al. Identification of cardiomyocyte nuclei and assessment of ploidy for the analysis of cell turnover. Exp Cell Res 2011; 317: 188-94.

10. Bergmann O, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte renewal in humans. Science 2009; 324: 98-102.

11. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOSTrandomised controlled clinical trial. Lancet 2004; 364: 141-48.

12. Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 1199-209.

13. Janssens S, Dubois C, Bogaert J, et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006; 367: 113-21.

14. Zimmet H, Porapakkham P, Porapakkham P, et al. Shortand long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. Eur J Heart Fail 2011; 14: 91-105.

15. Assmus B, Rolf A, Erbs S, et al, and the REPAIR-AMI Investigators. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail 2010; 3: 89-96.

16. Strauer BE, Yousef M, Schannwell CM. The acute and long-term effects ofintracoronary Stem cell Transplantation in 191 patients with chronic heARt failure: the STAR-heart study. Eur J Heart Fail 2010;12(7):721-9.

17. OrlicD, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-05.

18. Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2002;416: 542-45.

19. Mirotsou M, Jayawardena TM, Schmeckpeper J, et al. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 2011; 50: 280-89.

20. Goumans M-J, de Boer TP, Smits AM, et al.TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res 2007; 1: 138-49.

21. van Vliet P, Roccio M, Smits AM, et al. Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Neth Heart J 2008;16:163-9.

22. Smits AM, van Vliet P, Metz CH, et al. Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology. Nat Protoc 2009; 4:232-43.

23. Boer TPD, Veen TABV, Jonsson MKB, et al. Human cardiomyocyte progenitor cell derived cardiomyocytes display a maturated electrical phenotype. J Mol Cell Cardiol 2010; 48: 254-60.

24. van Vliet P, Smits AM, de Boer TP, et al. Foetal and adult cardiomyocyte progenitor cells have different developmental potential. J Cell Mol Med 2010; 14: 861-70.

25. Hierlihy AM, Seale P, Lobe CG, et al. The post-natal heart contains a myocardial stem cell population. FEBS Lett 2002; 530: 239-243.

26. Bearzi C, Rota M,Hosoda T, et al.Human cardiac stem cells. Proc NatlAcad Sci U SA2007;104:1406873.

27. Pevsner-Fischer M, Morad V, Cohen-Sfady M et al. Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 2007;109(4):1422-32.

28. Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 2003; 100: 12313-18,

29. Matsuura K, Nagai T, Nishigaki N, et al. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 2004; 279: 11384-91.

30. Hsieh PCH, Segers VFM, Davis ME, et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 2007;13:970-4.

31. Torella D, Ellison GM, Mèndez-Ferrer S, et al. Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med 2006;3(Suppl 1):s8-s13.

32. Smith RR, Barile L, Cho HC, et al. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endo¬myocardial biopsy specimens. Circulation 2007; 115: 896-908.

33. Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA 2005; 102: 8692-7.

34. Pouly J, Bruneval P, Mandet C, et al. Cardiac stem cells in the real world.J Thorac Cardiovasc Surg 2008; 135: 673-678.

35. Majno G, Joris I. Apoptosis, oncosis and necrosis. Am J Pathol 1995;146:3-15.

36. Kostin S. Pathways of myocyte death: implications for development of clinical laboratory biomarkers. Adv Clin Chem 2005;40:37-98.

37. Vigliano CA, Cabeza Meckert PM, Diez M, et al. Cardiomyocyte hypertrophy, oncosis, and autophagic vacuolization predict mortality in idiopathic dilated cardiomyopathy with advanced heart failure. J Am Coll Cardiol 2011;57:1523-31.

38. Kostin S, Pool L, Elsasser A, et al. Myocytes die by multiple mechanisms in failing human hearts. Circ Res 2003;92:715-24.

39. Hein S, Arnon E, Kostin S, et al. Progression from compensated hypertrophy to failure in the pressureoverloaded human heart: structural deterioration and compensatory mechanisms. Circulation 2003;107:984-91.

40. Elsasser A, Voigt AM, Nef H, et al. Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death. J Am Coll Cardiol 2004;43:2191-9.

41. Twerenbold R, Jaffe A, Reichlin T, Reiter M, Mueller C: High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J 2012; 33(5):579-86.

42. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 2011;304:250312.

43. Hessel MH, Michielsen EC, Atsma DE, et al. Release kinetics of intact and degraded troponin I and T after irreversible cell damage. Exp Mol Pathol 2008;85:90-5.

For citation:

Kulikova T.G., Stepanova O.V., Valihov M.P., Shhedrina A.Y., Samko A.N., Masenko V.P., Tereshhenko S.N. RESIDENT PROGENITOR CARDIAC CELLS IN PATIENTS WITH DILATED CARDIOMYOPATHY AND CONGESTIVE HEART FAILURE. Rational Pharmacotherapy in Cardiology. 2014;10(2):203-211. (In Russ.)

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