BIOLOGICAL AND CLINICAL RELEVANCE OF EARLY ENDOTHELIAL PROGENITOR CELLS RESEARCH

Endothelial Progenitor Cells (EPC) were first described in 1997 and since that they have been the subject of numerous investigative studies exploring the potential of these cells in the process of cardiovascular damage and repair. Whilst their exact definition and mechanism of action remains unclear, they are directly influenced by different cardiovascular risk factors and have a definite role to play in defining cardiovascular risk. We have studied the proliferative activity of early circulating EPC as well as the number of EPC endothelial colony-forming units (CFU-EC) in a carefully selected groups of patients: 18 with arterial hypertension, 19 - healthy control and 58 with chronic heart failure (36 with ischemic heart disease vs 36 with dilated cardiomyopathy). The study shows reduced CFU-EC as in patients with arterial hypertension and in patients with chronic heart failure. Changing the proliferative abilities of cells is closely related to pathological remodeling of the left ventricle and elevated SCORE index. Study colony-forming ability of early EPC maintains its position as an important prognostic biomarker reflecting the angiogenic potential.

циркулирующие эндотелиальные клетки-предшественники, гипертоническая болезнь, артериальная гипертензия, хроническая сердечная недостаточность, дилатационная кардиомиопатия, circulating endothelial progenitor cells, essential hypertension, dilated cardiomyopathy, ischemic heart disease

1. Asahara T., Murohara T., Sullivan A. et al. Isolation of putative endothelial progenitor cells for angiogenesis // Science. - 1997. - Vol. 275, № 5302. - P. 964-967.

2. Isner J.M., Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization // J. Clin. Invest. - 1999. - Vol. 103, № 9. - P. 1231-1236.

3. Kalka C., Masuda H., Takahashi T. et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization // Proc. Natl. Acad. Sci. USA. - 2000. - Vol. 97, № 7. - P. 3422-3427.

4. Hristov M., Erl W., Weber P.C. Endothelial progenitor cells: mobilization, differentiation, and homing // Arterioscler. Thromb. Vasc. Biol. - 2003. - Vol. 23, № 7. - P. 1185-1189.

5. Urbich C., Dimmeler S. Endothelial progenitor cells. Characterization and role in vascular biology // Cir. Res. - 2004. - Vol. 95, № 4. - P. 343-353.

6. Schatteman G.C., Dunnwald M., Jiao C. Biology of bone marrow-derived endothelial cell precursors // Am. J. Physiol. Heart Circ. Physiol. 2007. - Vol. 292, № 1. - P. H1-18.

7. Zampetaki A., Kirton J.P., Xu Q. Vascular repair by endothelial progenitor cells // Cardiovasc. Res. - 2008. - Vol. 78, № 3. - P. 413-421.

8. Timmermans F., Plum J., Yöder M.C. et al. Endothelial progenitor cells: identity defined? // J. Cell Mol. Med. - 2009. - Vol. 13, № 1. - P. 87-102.

9. Hill J.M., Zalos G., Halcox J.P.J. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk // N. Engl. J. Med. - 2003. - Vol. 348, № 7. - P. 593-600.

10. Werner N., Kosiol S., Schiegl T. et al. Circulating endothelial progenitor cells and cardiovascular outcomes // N. Engl. J. Med. - 2005. - Vol. 353, № 10. - P. 999-1007.

11. Rohde E., Bartmann C., Schallmoser K. et al. Immune Cells Mimic the Morphology of Endothelial Progenitor Colonies In Vitro // Stem Сеlls. - 2007. - Vol. 25, № 7. - P. 1746-1752.

12. Watt S.M., Athanassopoulos A., Harris A.L., Tsaknakis G. Human endothelial stem/progenitor cells, angiogenic factors and vascular repair // J. R. Soc. Interface. - 2010. -Vol. 7, Supp. 6. - P. S731-S751.

13. Devereux R.B., Reinchek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method // Circulation. - 1977. - Vol. 55, № 4. - P. 613-618.

14. Celermajer D.S., Soresen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis // Lancet. - 1992. - Vol. 340, № 8828. - P. 1111-1115.

15. Hirooka Y., Egashira K., Imaizumi T. et al. Effect of L-arginine on acetylcholine-induced endothelium-dependent vasodilation differs between the coronary and forearm vasculatures in humans // J. Am. Coll. Cardiol. - 1994. - Vol. 24, № 4. - P. 948-955.

16. Vogel R.A. Measurement of endothelial function by brachial artery flow-mediated vasodilatation // Am. J. Cardiol. - 2001. - Vol. 88, № 2A. - P. 31E-34E.

17. Peichev M., Naiyer A.J., Pereira D. et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors // Blood. - 2000. - Vol. 95, № 3. - P. 952-958.

18. Case J., Mead L.E., Bessler W.K. et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors // Exp. Hematol. - 2007. - Vol. 35, № 7. - P.1109-1118.

19. Harraz M., Jiao C., Hanlon H.D. et al. CD34-blood-derived human endothelial cell progenitors // Stem Cells. - 2001. - Vol. 19, № 4. - P. 304-312.

20. Rohde E., Malischnik C., Thaler D. et al. Blood Monocytes Mimic Endothelial Progenitor Cells // Stem Сells. - 2006. - Vol. 24, № 2. - P. 357-367.

21. Hirschi K.K., Ingram D.A., Yoder M.C. Assessing Identity, Phenotype, and Fate of Endothelial Progenitor Cells // Arterioscler. Thromb. Vasc. Biol. - 2008. - Vol. 28, № 9. - P. 1584-1595.

22. Elsheikh E., Uzunel M., He Z. et al. Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity // Blood. - 2005. - Vol. 106, № 7. - P. 2347-2355.

23. Zampetaki A., Kirton J.P., Xu Q. Vascular repair by endothelial progenitor cells // Cardiovasc. Res. - 2008. - Vol. 78, № 3. - P. 413-421.

24. Watt S.M., Gullo F., van der Garde M. et al. The angiogenic properties of mesenchymal stem/stromal cells and their therapeutic potential // British Medical Bulletin. - 2013. - Vol. 108. - P. 25-53.

25. Smith J.N.P., Calvi L.M. Concise Review: Current Concepts in Bone Marrow Microenvironmental Regulation of Hematopoietic Stem and Progenitor Cells // Stem Сells. - 2013. - Vol. 31, № 6. - P. 1044-1050.

26. Rehman J., Li J., Orschell C.M., March K.L. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors // Circulation. - 2003. - Vol. 107, № 8. - P. 1164-1169.

27. Fortini C., Toffoletto B., Fucili A. et al. Circulating stem cell vary with NYHA stage in heart failure patients // J. Cell. Mol. Med. - 2011. - Vol. 15, № 8. - P. 1726-1736.

28. Siddique A., Shantsila E., Lip G.Y., Varma C. Endothelial progenitor cells: what use for the cardiologist? // J. Angiogenes. Res. - 2010. - Feb 22; 2: 6. [Электронный ресурс] doi: 10.1186/2040-2384-2-6

29. Hayflick L., Moorhead P.S. The serial cultivation of human diploid cell strains // Exp. Cell Res. - 1961. - Vol. 25. - P. 585-621.

30. Chen J., Goligorsky M.S. Premature senescence of endothelial cells: Methusaleh’s dilemma // Am. J. Physiol. Heart Circ. Physiol. - 2006. - Vol. 290, № 5. - P. H1729-H1739.

31. Pu D.R., Liu L. HDL slowing down endothelial progenitor cells senescence: a novel anti-atherogenic property of HDL // Med. Hypotheses. - 2008. -Vol. 70, № 2. - P. 338-342.

32. Libby P., Ridker P.M., Hansson G.K. Inflammation in atherosclerosis: from pathophysiology to practice // J. Am. Coll. Cardiol. - 2009. - Vol. 54, № 23. - P. 2129-2138.

33. Verma S., Kuliszewski M.A., Shu-Hong Li et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation and function // Circulation. - 2004. - Vol. 109, № 17. - P. 2058-2067.

34. Spiel A.O., Mayr F.B., Leitner J.M. et al. Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation // Thromb Res. - 2008. - Vol. 123, № 1. - P. 108-113.

35. Kissel C.K., Lehmann R., Assmus B. et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure // J. Am. Coll. Cardiol. - 2007. - Vol. 49, № 24. - P. 2341-2349.