Mobilization of endothelial progenitor cells after endovascular interventions in patients with type 2 diabetes mellitus

Cover Page


To investigate the mobilisation of endothelial progenitor cells (EPC) in patients with type 2 diabetes mellitus (T2DM) after endovascular interventions for coronary and peripheral arteries.
Materials and Methods.
The levels of EPC in peripheral blood were determined by flow cytometry in 42 patients prior to endovascular intervention and 2?4 days after surgery. EPC were defined as CD34+ VEGFR2+ CD45- and CD34+ CD133+CD45- cells. Twenty-three patients with T2DM were included in group 1, and 19 patients without metabolic disorders were included in group 2.
The levels of EPC in the peripheral blood of patients with T2DM before and after endovascular interventions were not significantly different. In the subgroup of patients without TDM2, the levels of CD34+VEGFR2 +CD45- cells increased after surgery to 55,5% (p <0,01), and the levels of CD34 + CD133 + CD45- cells increased to 27,7% (p <0,05). After endovascular intervention for the subgroup of patients with T2DM and with the levels of HbA1c ?7,5%, the levels of CD34+VEGFR2+CD45- cells increased to 46,6% (p=0,01), and the levels of CD34+CD133+CD45- cells increased to 40,3 % (p=0,006) compared with the subgroup of patients with T2DM and with HbA1c levels of?7,5%.
The patients with T2DM displayed alterations in EPC mobilisation after endovascular interventions. In addition, the EPC level changes were dependent on glycaemic control. Thus, in the subgroup of patients with T2DM and with good glycaemic control (HbA1c ?7,5%), the EPC levels were significantly higher after endovascular interventions.

About the authors

Marina Sergeevna Michurova

Endocrinology Research Centre, Moscow

Author for correspondence.

Russian Federation MD, PhD-student of Diabetes institution

Victor Yur'evich Kalashnikov

Endocrinology Research Centre, Moscow


Russian Federation MD, PhD, Head of the Emergency and Interventional Cardiology Department

Olga Michailovna Smirnova

Endocrinology Research Centre, Moscow


Russian Federation MD, PhD, Professor, Chief Research Scientist, Department of Program Education and Treatment

Olga Nikolaevna Ivanova

Endocrinology Research Centre, Moscow


Russian Federation PhD, Head of Genetics and Clinical Immunology Laboratory

Sergey Anatol'evich Terekhin

Endocrinology Research Centre, Moscow


Russian Federation MD, PhD, Head of the X-Ray Endovascular Diagnosis and Treatment Room


  1. Avogaro A, de Kreutzenberg SV, Fadini G. Endothelial dysfunction: causes and consequences in patients with diabetes mellitus. Diabetes Research and Clinical Practice 2008;82(Suppl 2):94-101. Available from:
  2. Fadini GP. A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia 2013;57(1):4-15. Available from: PubMed PMID: 24173366. doi: 10.1007/s00125-013-3087-6.
  3. Van Craenenbroeck EM, Van Craenenbroeck AH, van Ierssel S, Bruyndonckx L, Hoymans VY, Vrints CJ, et al. Quantification of circulating CD34+/KDR+/CD45dim endothelial progenitor cells: Analytical considerations. International Journal of Cardiology 2013;167(5):1688-1695. Available from: PubMed PMID: 23171577. doi: 10.1016/j.ijcard.2012.10.047.
  4. Fadini GP. A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia 2014;57(1):4-15. Available from: PubMed PMID: 24173366. doi: 10.1007/s00125-013-3087-6.
  5. Schwartzenberg S, Afek A, Charach G, Rubinstein A, Ben-Shoshan Y, Kissil S, et al. Comparative analysis of the predictive power of different endothelial progenitor cell phenotypes on cardiovascular outcome. WJC 2010;2(9):299-304. Available from: PubMed PMID: 21160606. doi: 10.4330/wjc.v2.i9.299.
  6. Ingram DA. Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 2005;106(5):1525-1531. Available from: PubMed PMID: 15905185. doi: 10.1182/blood-2005-04-1509.
  7. Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs.. Fibrogenesis Tissue Repair 2012;5:4. Available from: PubMed PMID: 22410175. doi: 10.1186/1755-1536-5-4.
  8. Fadini GP, Boscaro E, de Kreutzenberg S, Agostini C, Seeger F, Dimmeler S, et al. Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes. Diabetes Care 2010;33(5):1097-1102. Available from: PubMed PMID: 20150295. doi: 10.2337/dc09-1999.
  9. Makino H, Okada S, Nagumo A, Sugisawa T, Miyamoto Y, Kishimoto I, et al. Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy. Diabet Med 2009;26(2):171-173. Available from: PubMed PMID: 19236621. doi: 10.1111/j.1464-5491.2008.02638.x.
  10. Fadini GP, Sartore S, Baesso I, Lenzi M, Agostini C, Tiengo A, et al. Endothelial Progenitor Cells and the Diabetic Paradox. Diabetes Care 2006;29(3):714-716. Available from: PubMed PMID: 16505536. doi: 10.2337/diacare.29.03.06.dc05-1834.
  11. Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA, et al. Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular Risk. N Engl J Med 2003;348(7):593-600. Available from: doi: 10.1056/NEJMoa022287.
  12. Fadini GP, Maruyama S, Ozaki T, Taguchi A, Meigs J, Dimmeler S, et al. Circulating progenitor cell count for cardiovascular risk stratification: A pooled analysis. PLoS One 2010;5:11488. Available from:
  13. Kunz GA, Liang G, Cuculi F, Gregg D, Vata KC, Shaw LK, et al. Circulating endothelial progenitor cells predict coronary artery disease severity. American Heart Journal 2006;152(1):190-195. Available from: doi: 10.1016/j.ahj.2006.02.001.
  14. Ghani U, Shuaib A, Salam A, Nasir A, Shuaib U, Jeerakathil T, et al. Endothelial Progenitor Cells During Cerebrovascular Disease. Stroke 2005;36(1):151-153. Available from: doi: 10.1161/01.STR.0000149944.15406.16.
  15. Fadini GP. Number and Function of Endothelial Progenitor Cells as a Marker of Severity for Diabetic Vasculopathy. Arteriosclerosis, Thrombosis, and Vascular Biology 2006;26(9):2140-2146. Available from: doi: 10.1161/01.ATV.0000237750.44469.88.
  16. David RB, Almeida ED, Cruz LV, Sebben JC, Feijó IP, Schmidt KE, et al. Diabetes mellitus and glucose as predictors of mortality in primary coronary percutaneous intervention. Arq Bras Cardiol 2014;103(4):323-330. Available from:
  17. Bonello L, Harhouri K, Baumstarck K, Arnaud L, Lesavre N, Piot C, et al. Mobilization of CD34+KDR+ endothelial progenitor cells predicts target lesion revascularization. Journal of Thrombosis and Haemostasis 2012;10(9):1906-1913. Available from: doi: 10.1111/j.1538-7836.2012.04854.x.
  18. Pelliccia F, Pasceri V, Rosano G, Pristipino C, Roncella A, Speciale G, et al. Endothelial Progenitor Cells Predict Long-Term Prognosis in Patients With Stable Angina Treated With Percutaneous Coronary Intervention. Circ J 2013;77(7):1728-1735. Available from: PubMed PMID: 23575363. doi: 10.1253/circj.CJ-12-1608.
  19. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007;45(Suppl S):5-67. Available from:
  20. Fadini GP, Albiero M, Vigili de Kreutzenberg, S, , Boscaro E, Cappellari R, Marescotti M, et al. Diabetes Impairs Stem Cell and Proangiogenic Cell Mobilization in Humans. Diabetes Care 2013;36(4):943-949. Available from: doi: 10.2337/dc12-1084.
  21. Kränkel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K, et al. Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells. Arteriosclerosis, Thrombosis, and Vascular Biology 2005;25(4):698-703. Available from: PubMed PMID: 15662022. doi: 10.1161/01.ATV.0000156401.04325.8f.
  22. Yiu KH, Tse HF. Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function. Arteriosclerosis, Thrombosis, and Vascular Biology 2014;34(6):1136-1143. Available from: PubMed PMID: 24743430. doi: 10.1161/ATVBAHA.114.302192.
  23. Oikawa A, Siragusa M, Quaini F, Mangialardi G, Katare RG, Caporali A, et al. Diabetes Mellitus Induces Bone Marrow Microangiopathy. Arteriosclerosis, Thrombosis, and Vascular Biology 2010;30(3):498-508. Available from: PubMed PMID: 20042708. doi: 10.1161/ATVBAHA.109.200154.
  24. Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, et al. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats. Diabetologia 2006;49(12):3075-3084. Available from: PubMed PMID: 17072586. doi: 10.1007/s00125-006-0401-6.
  25. Ferraro F, Lymperi S, Méndez-Ferrer S, Saez B, Spencer JA, Yeap BY, et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med 2011;3(104):104101. doi: 10.1126/scitranslmed.3002191.
  26. Ling L, Shen Y, Wang K, Jiang C, Fang C, Ferro A, et al. Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization. PLoS One 2012;7(11):50739. doi: 10.1371/journal.pone.0050739.
  27. Kochegura TN, Akopyan ZA, Sharonov GV, Efimenko AY, Ageev FT, Ovchinnikov AG, et al. The influence of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells in patients with ischemiccardiomyopathy. Diabetes mellitus 2011;3(3):36-43. Available from: doi: 10.14341/2072-0351-6222.
  28. Di Stefano R, Chiara Barsotti M, Felice F, Magera A, Lekakis J, Leone A, et al. Smoking and Endothelial Progenitor Cells: A Revision of Literature. CPD 2010;16(23):2559-2566. Available from: PubMed PMID: 20550506. doi: 10.2174/138161210792062939.
  29. Hoetzer GL, MacEneaney OJ, Irmiger HM, Keith R, Van Guilder GP, Stauffer BL, et al. Gender Differences in Circulating Endothelial Progenitor Cell Colony-Forming Capacity and Migratory Activity in Middle-Aged Adults. The American Journal of Cardiology 2007;99(1):46-48. Available from: PubMed PMID: 17196460. doi: 10.1016/j.amjcard.2006.07.061.
  30. Stauffer BL, MacEneaney OJ, Kushner EJ, Cech JN, Greiner JJ, Westby CM, et al. Gender and endothelial progenitor cell number in middle-aged adults. Artery Research 2008;2(4):156-160. Available from: doi: 10.1016/j.artres.2008.10.001.
  31. Humpert PM, Djuric Z, Zeuge U, Oikonomou D, Seregin Y, Laine K, et al. Insulin stimulates the clonogenic potential of angiogenic endothelial progenitor cells by IGF-1 receptor-dependent signaling. Mol Med 2008;14(5-6):301-308. Available from: PubMed PMID: 18309377. doi: 10.2119/2007-00052.Humpert.
  32. Marfella R, Rizzo MR, Siniscalchi M, Paolisso P, Barbieri M, Sardu C, et al. Peri-procedural tight glycemic control during early percutaneous coronary intervention up-regulates endothelial progenitor cell level and differentiation during acute ST-elevation myocardial infarction: Effects on myocardial salvage. International Journal of Cardiology 2013;168(4):3954-3962. Available from: PubMed PMID: 23876463. doi: 10.1016/j.ijcard.2013.06.053.
  33. António N, Fernandes R, Soares A, Soares F, Lopes A, Carvalheiro T, et al. Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum. CardiovascDiabetol 2014;13:101. Available from: doi: 10.1186/1475-2840-13-101.
  34. Chen L, Liao Y, Zeng T, Yu F, Li H, Feng Y. Effects of metformin plus gliclazide compared with metformin alone on circulating endothelial progenitor cell in type 2 diabetic patients. Endocr 2010;38(2):266-275. Available from: PubMed PMID: 20972736. doi: 10.1007/s12020-010-9383-8.
  35. Xiao-Yun X, Zhao-Hui M, Ke C, Hong-Hui H, Yan-Hong X. Glucagon-like peptide-1 improves proliferation and differentiation of endothelial progenitor cells via upregulating VEGF generation. Med Sci Monit 2011;17(2):35-41. Available from: PubMed PMID: 21278683.
  36. Gonçalves A, Leal E, Paiva A, Teixeira Lemos E, , Teixeira F, Ribeiro CF, et al. Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model. Diabetes ObesMetab 2012;14(5):454-463. Available from:
  37. Fadini GP, Avogaro A. Dipeptidyl peptidase-4 inhibition and vascular repair by mobilization of endogenous stem cells in diabetes and beyond. Atherosclerosis 2013;229(1):23-29. Available from: PubMed PMID: 23643052. doi: 10.1016/j.atherosclerosis.2013.04.007.

Supplementary files

There are no supplementary files to display.



Abstract - 1094

PDF (Russian) - 603




Copyright (c) 2014 Michurova M.S., Kalashnikov V.Y., Smirnova O.M., Ivanova O.N., Terekhin S.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies