diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM2015124-32diaendo-6771Research ArticleВопросы патогенезаPathogenesisРоль эндотелиальных прогениторных клеток в развитии осложнений сахарного диабетаEndothelial progenitor cells in diabetes complicationsМичуроваМарина СергеевнаMichurovaMarina Cergeevna

Аспирант 

michurovams@gmail.comКалашниковВиктор ЮрьевичKalashnikovVictor Yur'evichVictor9368@gmail.comСмирноваОльга МихайловнаSmirnovaOlga Michailovna

доктор медицинских наук, профессор, главный научный сотрудник отделения программного обучения и лечения

Dr_smr@mail.ruКононенкоИрина ВладимировнаKononenkoIrina Vladimirovna

кандидат медицинских наук, ведущий научный сотрудник отделения программного обучения и лечения

MD, PhD, Leading Researcher in Program Education and Treatment Department in Diabetes Institute.

Shakhtarina@bk.ruИвановаОльга НиколаевнаIvanovaOlga Nikolaevna

кандидат биологических наук, заведующая лабораторией генетики и клинической иммунологии

Genetics2@yandex.ruФГБУ "Эндокринологический научный центр" Минздрава России, МоскваРоссияEndocrinology Research Centre, MoscowRussian Federation2015201220141812432Copyright © Мичурова М.С., Калашников В.Ю., Смирнова О.М., Кононенко И.В., Иванова О.Н., 20152015Мичурова М.С., Калашников В.Ю., Смирнова О.М., Кононенко И.В., Иванова О.Н.Michurova M.C., Kalashnikov V.Y., Smirnova O.M., Kononenko I.V., Ivanova O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/6771

У больных сахарным диабетом (СД) риск развития сердечно-сосудистых заболеваний (ССЗ) в 2?4 раза выше, чем у больных без нарушения углеводного обмена. При СД хроническая гипергликемия запускает ряд патофизиологических механизмов, приводящих к повреждению эндотелия. В настоящее время считается, что в процессе восстановления эндотелия принимают участие циркулирующие клетки-предшественницы, выделяющиеся из костного мозга (КМ). Данные клетки, так называемые эндотелиальные прогениторные клетки (ЭПК), участвуют в поддержании функции эндотелия и способствуют его восстановлению после повреждения, а также образованию новых кровеносных сосудов. Многочисленные литературные данные показывают, что при СД наблюдается снижение количества и нарушение функции ЭПК. Кроме того, у больных СД нарушается адекватная реакция со стороны КМ в ответ на стимулирующие факторы. В данном обзоре рассмотрена роль ЭПК в развитии и прогрессировании микро- и макрососудистых осложнений СД.

Patients with diabetes mellitus (DM) have a 2- to 4-times higher risk of developing cardiovascular complications compared with non-diabetic controls. Hyperglycemia activates pathophysiological mechanisms that damage the endothelium. According to the current views, circulating progenitor cells derived from bone marrow repair the damage. These cells, known as endothelial progenitor cells (EPCs), maintain endothelial homeostasis and contribute to the formation of new vessels. Many clinical studies have reported that EPC population is dysfunctional and declines in numbers in patients with type 1 and type 2 DM. In addition, bone marrow doesn?t respond adequately to mobilizing stimuli in DM. Therefore, EPC alterations might have a pathogenic role in the complications of DM. In this review, EPC alterations will be examined in the context of macrovascular and microvascular complications of DM, highlighting their roles and functions in the progression of the disease.

сахарный диабетэндотелиальные прогениторные клеткиосложнения сахарного диабетасердечно-со- судистые заболеванияdiabetes mellitusendothelial progenitor cellsdiabetic complicationscardiovascular diseaseReferencesAvogaro 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:S94–S101. doi: 10.1016/j.diabres.2008.09.021Avogaro 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:S94–S101. doi: 10.1016/j.diabres.2008.09.021Brownlee M. The Pathobiology of Diabetic Complications: A Unifying Mechanism. Diabetes. 2005;54(6):1615–1625. doi: 10.2337/diabetes.54.6.1615.Brownlee M. The Pathobiology of Diabetic Complications: A Unifying Mechanism. Diabetes. 2005;54(6):1615–1625. doi: 10.2337/diabetes.54.6.1615.Asahara T. Isolation of Putative Progenitor Endothelial Cells for Angiogenesis. Science. 1997;275(5302):964–966. doi: 10.1126/science.275.5302.964.Asahara T. Isolation of Putative Progenitor Endothelial Cells for Angiogenesis. Science. 1997;275(5302):964–966. doi: 10.1126/science.275.5302.964.Ii M, Takenaka H, Asai J, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circulation research. 2006;98(5):697–704. doi: 10.1161/01.RES.0000209948.50943.eaIi M, Takenaka H, Asai J, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circulation research. 2006;98(5):697–704. doi: 10.1161/01.RES.0000209948.50943.eaHazarika S, Dokun AO, Li Y, et al. Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circulation research. 2007;101(9):948–956. doi: 10.1161/CIRCRESAHA.107.160630Hazarika S, Dokun AO, Li Y, et al. Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circulation research. 2007;101(9):948–956. doi: 10.1161/CIRCRESAHA.107.160630Fadini GP, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes care. 2007;30(5):1305–1313. doi: 10.2337/dc06-2305Fadini GP, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes care. 2007;30(5):1305–1313. doi: 10.2337/dc06-2305Authors/Task Force M, Ryden L, Grant PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). European heart journal. 2013;34(39):3035–3087. doi: 10.1093/eurheartj/eht108Authors/Task Force M, Ryden L, Grant PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). European heart journal. 2013;34(39):3035–3087. doi: 10.1093/eurheartj/eht108Khan SS, Solomon MA, McCoy JP. Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry Part B: Clinical Cytometry. 2005;64B(1):1–8. doi: 10.1002/cyto.b.20040.Khan SS, Solomon MA, McCoy JP. Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry Part B: Clinical Cytometry. 2005;64B(1):1–8. doi: 10.1002/cyto.b.20040.Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952–958.Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952–958.Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92(2):362–367.Shi Q, Rafii S, Wu MH, et al. Evidence for circulating bone marrow-derived endothelial cells. Blood. 1998;92(2):362–367.Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95(10):3106–3112.Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95(10):3106–3112.Masuda H, Alev C, Akimaru H, et al. Methodological development of a clonogenic assay to determine endothelial progenitor cell potential. Circulation research. 2011;109(1):20–37. doi: 10.1161/CIRCRESAHA.110.231837Masuda H, Alev C, Akimaru H, et al. Methodological development of a clonogenic assay to determine endothelial progenitor cell potential. Circulation research. 2011;109(1):20–37. doi: 10.1161/CIRCRESAHA.110.231837Case J, Mead LE, Bessler WK, et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp. Hematol. 2007;35(7):1109–1118. doi: 10.1016/j.exphem.2007.04.002.Case J, Mead LE, Bessler WK, et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp. Hematol. 2007;35(7):1109–1118. doi: 10.1016/j.exphem.2007.04.002.Bethel K, Luttgen MS, Damani S, et al. Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction. Physical biology. 2014;11(1):016002. doi: 10.1088/1478-3975/11/1/016002Bethel K, Luttgen MS, Damani S, et al. Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction. Physical biology. 2014;11(1):016002. doi: 10.1088/1478-3975/11/1/016002Hristov M, Erl W, Weber PC. Endothelial progenitor cells: isolation and characterization. Trends in cardiovascular medicine. 2003;13(5):201–206. doi: 10.1016/S1050-1738(03)00077-XHristov M, Erl W, Weber PC. Endothelial progenitor cells: isolation and characterization. Trends in cardiovascular medicine. 2003;13(5):201–206. doi: 10.1016/S1050-1738(03)00077-XFadini GP, Losordo D, Dimmeler S. Critical re-evaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circulation research. 2012;110(4):624–637. doi: 10.1161/CIRCRESAHA.111.243386Fadini GP, Losordo D, Dimmeler S. Critical re-evaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circulation research. 2012;110(4):624–637. doi: 10.1161/CIRCRESAHA.111.243386Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs. Fibrogenesis & tissue repair. 2012;5:4. doi: 10.1186/1755-1536-5-4Caiado F, Dias S. Endothelial progenitor cells and integrins: adhesive needs. Fibrogenesis & tissue repair. 2012;5:4. doi: 10.1186/1755-1536-5-4Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circulation research. 2004;95(4):343–353. doi: 10.1161/01.RES.0000137877.89448.78Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circulation research. 2004;95(4):343–353. doi: 10.1161/01.RES.0000137877.89448.78Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–864. doi: 10.1038/nm1075Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–864. doi: 10.1038/nm1075Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–637. doi: 10.1016/S0092-8674(02)00754-7Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–637. doi: 10.1016/S0092-8674(02)00754-7Krankel N, Adams V, Linke A, et al. Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arteriosclerosis, thrombosis, and vascular biology. 2005;25(4):698–703. doi: 10.1161/01.ATV.0000156401.04325.8fKrankel N, Adams V, Linke A, et al. Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arteriosclerosis, thrombosis, and vascular biology. 2005;25(4):698–703. doi: 10.1161/01.ATV.0000156401.04325.8fYiu 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. doi: 10.1161/ATVBAHA.114.302192Yiu 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. doi: 10.1161/ATVBAHA.114.302192Fadini GP. An underlying principle for the study of circulating progenitor cells in diabetes and its complications. Diabetologia. 2008;51(7):1091–1094. doi: 10.1007/s00125-008-1021-0Fadini GP. An underlying principle for the study of circulating progenitor cells in diabetes and its complications. Diabetologia. 2008;51(7):1091–1094. doi: 10.1007/s00125-008-1021-0Fadini GP, Pucci L, Vanacore R, et al. Glucose tolerance is negatively associated with circulating progenitor cell levels. Diabetologia. 2007;50(10):2156–2163. doi: 10.1007/s00125-007-0732-yFadini GP, Pucci L, Vanacore R, et al. Glucose tolerance is negatively associated with circulating progenitor cell levels. Diabetologia. 2007;50(10):2156–2163. doi: 10.1007/s00125-007-0732-yTepper OM, Galiano RD, Capla JM, et al. Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures. Circulation. 2002;106(22):2781–2786. doi: 10.1161/01.cir.0000039526.42991.93Tepper OM, Galiano RD, Capla JM, et al. Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures. Circulation. 2002;106(22):2781–2786. doi: 10.1161/01.cir.0000039526.42991.93Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53(1):195–199. doi: 10.2337/diabetes.53.1.195Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53(1):195–199. doi: 10.2337/diabetes.53.1.195Кочегура Т.Н., Акопян Ж.А., Шаронов Г.В., и др. Влияние сопутствующего сахарного диабета 2 типа на количество циркулирующих прогениторных клеток у больных с ишемической кардиомиопатией. // Сахарный диабет. – 2011. – №3 – С. 36–43. [Kochegura TN, Akopyan ZA, Sharonov GV, et al. The influence of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells in patients with ischemic cardiomyopathy. Diabetes mellitus. 2011;14(3):36–43.] doi: 10.14341/2072-0351-6222Кочегура Т.Н., Акопян Ж.А., Шаронов Г.В., и др. Влияние сопутствующего сахарного диабета 2 типа на количество циркулирующих прогениторных клеток у больных с ишемической кардиомиопатией. // Сахарный диабет. – 2011. – №3 – С. 36–43. [Kochegura TN, Akopyan ZA, Sharonov GV, et al. The influence of concomitant type 2 diabetes mellitus on the number of circulating progenitor cells in patients with ischemic cardiomyopathy. Diabetes mellitus. 2011;14(3):36–43.] doi: 10.14341/2072-0351-6222Dessapt C, Karalliedde J, Hernandez-Fuentes M, et al. Circulating vascular progenitor cells in patients with type 1 diabetes and microalbuminuria. Diabetes care. 2010;33(4):875–877. doi: 10.2337/dc09-1468.Dessapt C, Karalliedde J, Hernandez-Fuentes M, et al. Circulating vascular progenitor cells in patients with type 1 diabetes and microalbuminuria. Diabetes care. 2010;33(4):875–877. doi: 10.2337/dc09-1468.Brunner S, Schernthaner GH, Satler M, et al. Correlation of different circulating endothelial progenitor cells to stages of diabetic retinopathy: first in vivo data. Investigative ophthalmology & visual science. 2009;50(1):392–398. doi: 10.1167/iovs.08-1748Brunner S, Schernthaner GH, Satler M, et al. Correlation of different circulating endothelial progenitor cells to stages of diabetic retinopathy: first in vivo data. Investigative ophthalmology & visual science. 2009;50(1):392–398. doi: 10.1167/iovs.08-1748Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. Journal of the American College of Cardiology. 2005;45(9):1449–1457. doi: 10.1016/j.jacc.2004.11.067Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. Journal of the American College of Cardiology. 2005;45(9):1449–1457. doi: 10.1016/j.jacc.2004.11.067Choi JH, Kim KL, Huh W, et al. Decreased number and impaired angiogenic function of endothelial progenitor cells in patients with chronic renal failure. Arteriosclerosis, thrombosis, and vascular biology. 2004;24(7):1246–1252. doi: 10.1161/01.ATV.0000133488.56221.4aChoi JH, Kim KL, Huh W, et al. Decreased number and impaired angiogenic function of endothelial progenitor cells in patients with chronic renal failure. Arteriosclerosis, thrombosis, and vascular biology. 2004;24(7):1246–1252. doi: 10.1161/01.ATV.0000133488.56221.4aThum T, Tsikas D, Stein S, et al. Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Journal of the American College of Cardiology. 2005;46(9):1693–1701. doi: 10.1016/j.jacc.2005.04.066Thum T, Tsikas D, Stein S, et al. Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Journal of the American College of Cardiology. 2005;46(9):1693–1701. doi: 10.1016/j.jacc.2005.04.066Bahlmann FH, De Groot K, Spandau JM, et al. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103(3):921–926. doi: 10.1182/blood-2003-04-1284Bahlmann FH, De Groot K, Spandau JM, et al. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103(3):921–926. doi: 10.1182/blood-2003-04-1284Herbrig K, Gebler K, Oelschlaegel U, et al. Kidney transplantation substantially improves endothelial progenitor cell dysfunction in patients with end-stage renal disease. American journal of transplantation. 2006;6(12):2922–2928. doi: 10.1111/j.1600-6143.2006.01555.xHerbrig K, Gebler K, Oelschlaegel U, et al. Kidney transplantation substantially improves endothelial progenitor cell dysfunction in patients with end-stage renal disease. American journal of transplantation. 2006;6(12):2922–2928. doi: 10.1111/j.1600-6143.2006.01555.xMakino H, Okada S, Nagumo A, et al. Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy. Diabetic medicine. 2009;26(2):171–173. doi: 10.1111/j.1464-5491.2008.02638.xMakino H, Okada S, Nagumo A, et al. Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy. Diabetic medicine. 2009;26(2):171–173. doi: 10.1111/j.1464-5491.2008.02638.xButler JM, Guthrie SM, Koc M, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. Journal of Clinical Investigation. 2005;115(1):86–93. doi: 10.1172/JCI200522869Butler JM, Guthrie SM, Koc M, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. Journal of Clinical Investigation. 2005;115(1):86–93. doi: 10.1172/JCI200522869Fadini GP, Sartore S, Baesso I, et al. Endothelial progenitor cells and the diabetic paradox. Diabetes care. 2006;29(3):714–716. doi: 10.2337/diacare.29.03.06.dc05-1834Fadini GP, Sartore S, Baesso I, et al. Endothelial progenitor cells and the diabetic paradox. Diabetes care. 2006;29(3):714–716. doi: 10.2337/diacare.29.03.06.dc05-1834Asnaghi V, Lattanzio R, Mazzolari G, et al. Increased clonogenic potential of circulating endothelial progenitor cells in patients with type 1 diabetes and proliferative retinopathy. Diabetologia. 2006;49(5):1109–1111. doi: 10.1007/s00125-006-0180-0Asnaghi V, Lattanzio R, Mazzolari G, et al. Increased clonogenic potential of circulating endothelial progenitor cells in patients with type 1 diabetes and proliferative retinopathy. Diabetologia. 2006;49(5):1109–1111. doi: 10.1007/s00125-006-0180-0Tan K, Lessieur E, Cutler A, et al. Impaired function of circulating CD34(+) CD45(-) cells in patients with proliferative diabetic retinopathy. Experimental eye research. 2010;91(2):229–237. doi: 10.1016/j.exer.2010.05.012Tan K, Lessieur E, Cutler A, et al. Impaired function of circulating CD34(+) CD45(-) cells in patients with proliferative diabetic retinopathy. Experimental eye research. 2010;91(2):229–237. doi: 10.1016/j.exer.2010.05.012Fadini GP. Is bone marrow another target of diabetic complications? European journal of clinical investigation. 2011;41(4):457–463. doi: 10.1111/j.1365-2362.2010.02417.xFadini GP. Is bone marrow another target of diabetic complications? European journal of clinical investigation. 2011;41(4):457–463. doi: 10.1111/j.1365-2362.2010.02417.xFerraro F, Lymperi S, Mendez-Ferrer S, et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Science translational medicine. 2011;3(104):104ra101. doi: 10.1126/scitranslmed.3002191Ferraro F, Lymperi S, Mendez-Ferrer S, et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Science translational medicine. 2011;3(104):104ra101. doi: 10.1126/scitranslmed.3002191Fadini GP, Albiero M, Vigili de Kreutzenberg S, et al. Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes care. 2013;36(4):943–949. doi: 10.2337/dc12-1084Fadini GP, Albiero M, Vigili de Kreutzenberg S, et al. Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes care. 2013;36(4):943–949. doi: 10.2337/dc12-1084Fadini GP, Ferraro F, Quaini F, et al. Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration. Stem cells translational medicine. 2014;3(8):949–957. doi: 10.5966/sctm.2014-0052Fadini GP, Ferraro F, Quaini F, et al. Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration. Stem cells translational medicine. 2014;3(8):949–957. doi: 10.5966/sctm.2014-0052Fadini GP. A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia. 2014;57(1):4–15. doi: 10.1007/s00125-013-3087-6Fadini GP. A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia. 2014;57(1):4–15. doi: 10.1007/s00125-013-3087-6Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. The New England journal of medicine. 2003;348(7):593–600. doi: 10.1056/NEJMoa022287Hill JM, Zalos G, Halcox JP, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. The New England journal of medicine. 2003;348(7):593–600. doi: 10.1056/NEJMoa022287Vasa M, Fichtlscherer S, Aicher A, et al. Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease. Circulation research. 2001;89(1):e1–e7. doi: 10.1161/hh1301.093953Vasa M, Fichtlscherer S, Aicher A, et al. Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease. Circulation research. 2001;89(1):e1–e7. doi: 10.1161/hh1301.093953Sibal L, Aldibbiat A, Agarwal SC, et al. Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia. 2009;52(8):1464–1473. doi: 10.1007/s00125-009-1401-0Sibal L, Aldibbiat A, Agarwal SC, et al. Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia. 2009;52(8):1464–1473. doi: 10.1007/s00125-009-1401-0Fadini GP, Coracina A, Baesso I, et al. Peripheral Blood CD34+KDR+ Endothelial Progenitor Cells Are Determinants of Subclinical Atherosclerosis in a Middle-Aged General Population. Stroke. 2006;37(9):2277–2282. doi: 10.1161/01.str.0000236064.19293.79Fadini GP, Coracina A, Baesso I, et al. Peripheral Blood CD34+KDR+ Endothelial Progenitor Cells Are Determinants of Subclinical Atherosclerosis in a Middle-Aged General Population. Stroke. 2006;37(9):2277–2282. doi: 10.1161/01.str.0000236064.19293.79Kunz GA, Liang G, Cuculi F, et al. Circulating endothelial progenitor cells predict coronary artery disease severity. American heart journal. 2006;152(1):190–195. doi: 10.1016/j.ahj.2006.02.001Kunz GA, Liang G, Cuculi F, et al. Circulating endothelial progenitor cells predict coronary artery disease severity. American heart journal. 2006;152(1):190–195. doi: 10.1016/j.ahj.2006.02.001Fadini GP, Sartore S, Albiero M, et al. 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. doi: 10.1161/01.atv.0000237750.44469.88Fadini GP, Sartore S, Albiero M, et al. 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. doi: 10.1161/01.atv.0000237750.44469.88Massa M, Rosti V, Ferrario M, et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2004;105(1):199–206. DOI:10.1182/blood-2004-05-1831Massa M, Rosti V, Ferrario M, et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2004;105(1):199–206. DOI:10.1182/blood-2004-05-1831Marti-Fabregas J, Crespo J, Delgado-Mederos R, et al. Endothelial progenitor cells in acute ischemic stroke. Brain and behavior. 2013;3(6):649–655. doi: 10.1002/brb3.175Marti-Fabregas J, Crespo J, Delgado-Mederos R, et al. Endothelial progenitor cells in acute ischemic stroke. Brain and behavior. 2013;3(6):649–655. doi: 10.1002/brb3.175Руда М.М., Арефьева Т.И., Соколова А.В., и др. Циркулирующие предшественники эндотелиальных клеток при нарушенном углеводном обмене у больных ишемической болезнью сердца. // Сахарный диабет. – 2010. – №1. – С. 13–20. [Ruda MM, Aref'eva TI, Sokolova AV, Shestakova MV, Karpov YA, Parfenova EV. Circulating precursors of endothelial cells in patients with CHD and disturbed carbohydrate metabolism. Diabetes mellitus. 2010;13(1):13–20]. doi: 10.14341/2072-0351-6011Руда М.М., Арефьева Т.И., Соколова А.В., и др. Циркулирующие предшественники эндотелиальных клеток при нарушенном углеводном обмене у больных ишемической болезнью сердца. // Сахарный диабет. – 2010. – №1. – С. 13–20. [Ruda MM, Aref'eva TI, Sokolova AV, Shestakova MV, Karpov YA, Parfenova EV. Circulating precursors of endothelial cells in patients with CHD and disturbed carbohydrate metabolism. Diabetes mellitus. 2010;13(1):13–20]. doi: 10.14341/2072-0351-6011Ling L, Shen Y, Wang K, 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):e50739. doi: 10.1371/journal.pone.0050739Ling L, Shen Y, Wang K, 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):e50739. doi: 10.1371/journal.pone.0050739Antonio N, Fernandes R, Soares A, et al. Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum. Cardiovascular diabetology. 2014;13:101. doi: 10.1186/1475-2840-13-101Antonio N, Fernandes R, Soares A, et al. Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum. Cardiovascular diabetology. 2014;13:101. doi: 10.1186/1475-2840-13-101Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. The New England journal of medicine. 2005;353(10):999–1007. doi: 10.1056/NEJMoa043814Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. The New England journal of medicine. 2005;353(10):999–1007. doi: 10.1056/NEJMoa043814Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111(22):2981–2987. doi: 10.1161/CIRCULATIONAHA.104.504340Schmidt-Lucke C, Rossig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111(22):2981–2987. doi: 10.1161/CIRCULATIONAHA.104.504340Schwartzenberg S, Afek A, Charach G, et al. Comparative analysis of the predictive power of different endothelial progenitor cell phenotypes on cardiovascular outcome. World journal of cardiology. 2010;2(9):299–304. doi: 10.4330/wjc.v2.i9.299Schwartzenberg S, Afek A, Charach G, et al. Comparative analysis of the predictive power of different endothelial progenitor cell phenotypes on cardiovascular outcome. World journal of cardiology. 2010;2(9):299–304. doi: 10.4330/wjc.v2.i9.299Fadini GP, Maruyama S, Ozaki T, et al. Circulating progenitor cell count for cardiovascular risk stratification: a pooled analysis. PloS one. 2010;5(7):e11488. doi: 10.1371/journal.pone.0011488Fadini GP, Maruyama S, Ozaki T, et al. Circulating progenitor cell count for cardiovascular risk stratification: a pooled analysis. PloS one. 2010;5(7):e11488. doi: 10.1371/journal.pone.0011488Inoue T, Croce K, Morooka T, et al. Vascular Inflammation and Repair: Implications for Reendothelialization, Restenosis, and Stent Thrombosis. JACC Cardiovascular Interventions. 2011;4(10):1057–1066. doi: 10.1016/j.jcin.2011.05.025Inoue T, Croce K, Morooka T, et al. Vascular Inflammation and Repair: Implications for Reendothelialization, Restenosis, and Stent Thrombosis. JACC Cardiovascular Interventions. 2011;4(10):1057–1066. doi: 10.1016/j.jcin.2011.05.025Bonello L, Harhouri K, Baumstarck K, et al. Mobilization of CD34+KDR+ endothelial progenitor cells predicts target lesion revascularization. Journal of Thrombosis and Haemostasis. 2012;10(9):1906–1913. doi: 10.1111/j.1538-7836.2012.04854.xBonello L, Harhouri K, Baumstarck K, et al. Mobilization of CD34+KDR+ endothelial progenitor cells predicts target lesion revascularization. Journal of Thrombosis and Haemostasis. 2012;10(9):1906–1913. doi: 10.1111/j.1538-7836.2012.04854.xPelliccia F, Cianfrocca C, Rosano G, et al. Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention: a prospective study. JACC Cardiovascular Interventions.. 2010;3(1):78–86. doi: 10.1016/j.jcin.2009.10.020Pelliccia F, Cianfrocca C, Rosano G, et al. Role of endothelial progenitor cells in restenosis and progression of coronary atherosclerosis after percutaneous coronary intervention: a prospective study. JACC Cardiovascular Interventions.. 2010;3(1):78–86. doi: 10.1016/j.jcin.2009.10.020Pelliccia F, Pasceri V, Rosano G, et al. Endothelial progenitor cells predict long-term prognosis in patients with stable angina treated with percutaneous coronary intervention: five-year follow-up of the PROCREATION study. Circulation journal. 2013;77(7):1728–1735. doi: 10.1253/circj.CJ-12-1608Pelliccia F, Pasceri V, Rosano G, et al. Endothelial progenitor cells predict long-term prognosis in patients with stable angina treated with percutaneous coronary intervention: five-year follow-up of the PROCREATION study. Circulation journal. 2013;77(7):1728–1735. doi: 10.1253/circj.CJ-12-1608Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). European journal of cardio-thoracic surgery. 2014;46(4):517-592. doi: 10.1093/ejcts/ezu366Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). European journal of cardio-thoracic surgery. 2014;46(4):517-592. doi: 10.1093/ejcts/ezu366Zhao CT, Wang M, Siu CW, et al. Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress. Cardiovascular diabetology. 2012;11:147. doi: 10.1186/1475-2840-11-147Zhao CT, Wang M, Siu CW, et al. Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress. Cardiovascular diabetology. 2012;11:147. doi: 10.1186/1475-2840-11-147

The authors declare that there are no conflicts of interest present.