Endothelial Progenitor Cells in Diabetic Vasculopathy
Abstract
BACKGROUND: The discovery of endothelial progenitor cell (EPC) a decade ago by Asahara, et al has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The reduced circulating concentration of EPCs is a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases.
CONTENT: Diabetes is linked to impaired vascular function, including alterations in both endothelial cells and EPCs. A number of studies have shown that individuals with diabetes have decreased level of circulating EPCs and that the severity of disease is inversely proportional to EPC levels. In vitro, hyperglycemia increases the rate of EPC senescence and the angiogenic function of EPCs from patients with either type 1 or type 2 diabetes is impaired such that they are poorly proliferative and fail to incorporate into forming vessel-like structures. Given the comprehensive role of EPC alterations in diabetes complications, modulation of the levels and/or function of EPCs may be considered a potential therapeutic strategy.
SUMMARY: The available data demonstrating that decrease or dysfunction of EPCs may have a prominent role in the pathogenesis of all diabetes complications. Further approaches, such as EPC administration, may represent novel treatments for diabetic vasculopathy in the future. To date, many barriers remain to such a therapeutic approach. Firstly, there is no specific marker for EPC at present. Secondly, techniques of EPC isolation are not standardized, preventing direct comparison between various studies. The long-term effects of transplanted EPCs are currently unknown.
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Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275: 964-6, CrossRef.
Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA. 2000; 97: 3422-7, CrossRef.
Kubota Y, Kishi K, Satoh H, Tanaka T, Nakajima H, Nakajima T. Transplanted endothelial progenitor cells augment the survival areas of rat dorsal flaps. Cell Transplant. 2003; 12: 647-57, CrossRef.
Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation. 2003; 108: 2710-5, CrossRef.
He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004; 35: 2378-84, CrossRef.
Takahashi M, Nakamura T, Toba T, Kajiwara N, Kato H, Shimizu Y. Transplantation of endothelial progenitor cells into the lung to alleviate pulmonary hypertension in dogs. Tissue Eng. 2004; 10: 771-9, CrossRef.
Imanishi T, Moriwaki C, Hano T, Nishio I. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens. 2005; 23: 1831-7, CrossRef.
Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107: 273-80, CrossRef.
Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, et al. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol. 2004; 24: 1442-47, CrossRef.
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascularrisk. N Engl J Med. 2003; 348: 593-600, CrossRef.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005; 353: 999-1007, CrossRef.
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, 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: 2981-7, CrossRef.
Segal MS, Shah R, Afzal A, Perrault CM, Chang K, Schuler A, et al. Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes. 2006; 55: 102-9, CrossRef.
Ii M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, Maruyama K, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res. 2006; 98: 697-704, CrossRef.
Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, et al. Diabetes impairs progenitor cell mobilization after hindlimb ischemiareperfusion injury in rats. Diabetologia. 2006; 49: 3075-84, CrossRef.
Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W, 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, CrossRef.
Kang HJ, Lee HY, Na SH, Chang SA, Park KW, Kim HK, et al. Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial. Circulation. 2006; 114: I145–I151, CrossRef.
Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002; 106: 1913-8, CrossRef.
Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, et al. Intracoronary autologous bonemarrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004; 364: 141-8, CrossRef.
Erbs S, Linke A, Adams V, Lenk K, Thiele H, Diederich KW, et al. Transplantation of blood-derived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebocontrolled study. Circ Res. 2005; 97: 756-62, CrossRef.
Strauer BE, Brehm M, Zeus T, Bartsch T, Schannwell C, Antke C, et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol. 2005; 46: 1651-8, CrossRef.
Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003; 107: 2294-302, CrossRef.
Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factormobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005; 28: 2155-60, CrossRef.
Saigawa T, Kato K, Ozawa T, Toba K, Makiyama Y, Minagawa S, et al. Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells. Circ J. 2004; 68: 1189-93, CrossRef.
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002; 360: 427-435, CrossRef.
Tse HF, Thambar S, Kwong YL, Rowlings P, Bellamy G, McCrohon J, et al. Safety of catheter-based intramyocardial autologous bone marrow cells implantation for therapeutic angiogenesis. Am J Cardiol. 2006; 98: 60-2, CrossRef.
Fadini GP, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care. 2007; 30: 1305-13, CrossRef.
Akasaka T, Yoshida K, Hozumi T, Takagi T, Kaji S, Kawamoto T, et al. Retinopathy identifies marked restriction of coronary flow reserve in patients with diabetes mellitus. J Am Coll Cardiol. 1997; 30: 935-41, CrossRef.
Klein BE, Klein R, McBride PE, Cruickshanks KJ, Palta M, Knudtson MD, et al. Cardiovascular disease, mortality, and retinal microvascular characteristics in type 1 diabetes: Wisconsin Epidemiologic Study of Diabetic Retinopathy. Arch Intern Med. 2004; 164: 1917-24, CrossRef.
Brownlee M. The pathobiology of diabetic complications: a unified mechanism. Diabetes. 2005; 54: 1615-25, CrossRef.
Fadini GP, Agostini C, Avogaro A. Characterization of endothelial progenitor cells. Biochem Biophys Res Commun. 2005; 336: 1-2, CrossRef.
Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005; 45: 321-5, CrossRef.
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, et al. Ischemia- and cytokineinduced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999; 5: 434-8, PMID.
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005; 353: 999-1007, CrossRef.
Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000; 95: 3106-12, PMID.
Handgretinger R, Gordon PR, Leimig T, Chen X, Buhring HJ, Niethammer D, et al. Biology and plasticity of CD133 + hematopoietic stem cells. Ann NY Acad Sci. 2003; 996: 141-51, CrossRef.
Mutin M, Canavy I, Blann A, Bory M, Sampol J, Dignat-George F. Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood. 1999; 93: 2951-8, PMID.
Urbich C, Dimmeler S. Endothelial progenitor cells: Characterization and role in vascular biology. Circ Res. 2004; 95: 343-3, CrossRef.
Liew A, McDermott JH, Barry F, O’Brien T. Endothelial progenitor cells for the treatment of diabetic vasculopathy: panacea or pandora’s box? Diabetes Obes Metab. 2008; 10: 353-66, CrossRef.
Rustemeyer P, Wittkowski W, Jurk K, Koller A. Optimized flow cytometric analysis of endothelial progenitor cells in peripheral blood. J Immunoassay Immunochem. 2006; 27: 77-8, CrossRef.
Hur J, Yon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol. 2004; 24: 288-93, CrossRef.
Yoon CH, Hur J, Park KW, Kim JH, Lee CS, Oh IY, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: The role of angiogenic cytokines and matrix metalloproteinases. Circulation, 2005; 112: 1618-27, CrossRef.
Isner JM, Asahara T. Angiogenesis and vasculogenesis as therapeutic strategies for postnatal neovascularization. J Clin Invest. 1999; 103: 1231-6, CrossRef.
Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003; 107: 1164-9, CrossRef.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995; 1: 27-31, CrossRef.
Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002; 105: 3017-24, CrossRef.
Werner N, Junk S, Laufs U, Link A, Walenta K, Bohm M, et al. Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res. 2003; 93: e17-24, CrossRef.
Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001; 7: 1035-40, PMID.
Hillebrands JL, Klatter FA, van Dijk WD, Rozing J. Bone marrow does not contribute substantially to endothelial-cell replacement in transplant arteriosclerosis. Nat Med. 2002; 8: 194-5, CrossRef.
Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation. 2003; 108: 2710-5, CrossRef.
Fujiyama S, Amano K, Uehira K, Yoshida M, Nishiwaki Y, Nozawa Y, et al. Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Circ Res. 2003; 93: 980-9, CrossRef.
Hu Y, Davison F, Zhang Z, Xu Q. Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells. Circulation. 2003; 108: 3122-7, CrossRef.
Silvestre JS, Gojova A, Brun V, Potteaux S, Esposito B, Duriez M, et al. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation. 2003; 108: 2839-42, CrossRef.
Rossig L, Dimmeler S, Zeiher AM. Apoptosis in the vascular wall and atherosclerosis. Basic Res Cardiol. 2001; 96: 11-22, CrossRef.
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001; 89: e1-7, CrossRef.
Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest. 2001; 108: 399-405, CrossRef.
Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001; 103: 2885-90, CrossRef.
Laufs U, Werner N, Link A, Endres M, Wassmann S, Jurgens K, et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation. 2004; 109: 220-6, CrossRef.
Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002; 109: 625-37, CrossRef.
Hristov M, Erl W, Weber PC. Endothelial progenitor cells: Mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. 2003; 23: 1185-9, CrossRef.
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425: 841-6, CrossRef.
Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem cell biology. Cell. 1997; 88: 287-98, CrossRef.
Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003; 425: 836-41, CrossRef.
Lapidot T, Petit I. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol. 2002; 30: 973-81, CrossRef.
Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ. Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood. 2001; 98: 1289-97, CrossRef.
Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003; 111: 187-96, CrossRef.
Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, et al Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97: 3354-60, CrossRef.
Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med. 2002; 8: 841-9, CrossRef.
Robinson SN, Pisarev VM, Chavez JM, Singh RK, Talmadge JE. Use of matrix metalloproteinase (MMP)-9 knockout mice demonstrates that MMP-9 activity is not absolutely required for G-CSF or Flt-3 ligandinduced hematopoietic progenitor cell mobilization or engraftment. Stem Cells. 2003; 21: 417-27, CrossRef.
Levesque JP, Liu F, Simmons PJ, Betsuyaku T, Senior RM, Pham C, et al. Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood. 2004; 104: 65-72, CrossRef.
Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004; 110: 1933-9, CrossRef.
Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003; 9: 1370-6, CrossRef.
Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrowderived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation. 2003; 108: 3115-21, CrossRef.
Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002; 106: 2781-6, CrossRef.
Li B, Sharpe EE, Maupin AB, Teleron AA, Pyle AL, Carmeliet P, et al. VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization. FASEB J. 2006; 20: 1495-7, CrossRef.
Gassmann M, Fandrey J, Bichet S, Wartenberg M, Marti HH, Bauer C, et al. Oxygen supply and oxygen-dependent gene expression in differentiating embryonic stem cells. Proc Natl Acad Sci USA.1996; 93: 2867-72, CrossRef.
Hoper J, Jahn H. Influence of environmental oxygen concentration on growth and vascular density of the area vasculosa in chick embryos. Int J Microcirc Clin Exp. 1995; 15: 186-92, CrossRef.
Ramirez-Bergeron DL, Runge A, Adelman DM, Gohil M, Simon MC. HIF-dependent hematopoietic factors regulate the development of the embryonic vasculature. Dev Cell. 2006; 11: 81-92, CrossRef.
Yue X, Tomanek RJ. Effects of VEGF(165) and VEGF(121) on vasculogenesis and angiogenesis in cultured embryonic quail hearts. Am J Physiol. 2001; 280: H2240-7, PMID.
Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10: 858-64, CrossRef.
Schmidt A, Brixius K, Bloch W. Endothelial progenitor cells migration during vasculogenesis. Circ Res. 2007; 101: 125-36, CrossRef.
Li X, Han Y, Pang W, Li C, Xie X, Shyy JYJ, et al. AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008; 28: 1789-95, CrossRef.
Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med. 2006; 12: 557-67, CrossRef.
Massberg S, Konrad I, Schurzinger K, Lorenz M, Schneider S, Zohlnhoefer D, et al. Platelets secrete stromal cell-derived factor 1 and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med. 2006; 203: 1221-33, CrossRef.
Zernecke A, Schober A, Bot I, von Hundelshausen P, Liehn EA, Mopps B, et al. SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res. 2005; 96: 784-91, CrossRef.
Rafii DC, Psaila B, Butler J, Jin DK, Lyden D. Regulation of vasculogenesis by platelet-mediated recruitment of bone marrow-derived cells. Arterioscler Thromb Vasc Biol. 2008; 28: 217-22, CrossRef.
Chavakis E, Carmona G, Urbich C, Gottig S, Henschler R, Penninger JM. Phosphatidylinositol-3-kinase -γ is integral to homing functions of progenitor cells. Circ Res. 2008; 102: 942-9, CrossRef.
Mallat Z. PI3Kγ helps an SDF seeking home . . . for EPCs. Circ Res. 2008; 102: 871-2, CrossRef.
Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med. 2001; 7: 1194-201, PMID.
Imanishi T, Hano T, Nishio I. Angiotensin II potentiates vascular endothelial growth factor-induced proliferation and network formation of endothelial progenitor cells. Hypertens Res. 2004; 27: 101-8, CrossRef.
Loomans CJ, De Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, De Boer HC, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004; 53: 195-9, CrossRef.
Imanishi T, Hano T, Sawamura T, Nishio I. Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol. 2004; 31: 407-13, CrossRef.
Tso C, Martinic G, Fan WH, Rogers C, Rye KA, Barter PJ. High-density lippoproteins enhance progenitor-mediated endothelium repair in mice. Arterioscler Thromb Vasc Biol. 2006; 26: 1144-9, CrossRef.
Wang X, Zhu J, Chen J, Shang Y. Effects of nicotine on the number and activity of circulating endothelial progenitor cells. J Clin Pharmacol. 2004; 44: 881-9, CrossRef.
Sandri M, Adams V, Gielen S, Linke A, Lenk K, Krankel N, et al. Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation. 2005; 111: 3391-9, CrossRef.
Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, et al. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005; 12: 407-14, CrossRef.
Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, et al. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: Further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation. 2004; 109: 2058-67, CrossRef.
Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR. A stem cell molecular signature. Science. 2002; 298: 601-4, CrossRef.
Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA. “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science. 2002; 298: 597-600, CrossRef.
He T, Peterson TE, Holmuhamedov EL, Terzic A, Caplice NM, Oberley LW, et al. Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler Thromb Vasc Biol. 2004; 24: 2021-7, CrossRef.
Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, et al. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation. 2005; 111: 1763-70, CrossRef.
Colak E, Majkic-Singh N, Stankovic S, Sreckovic-Dimitrijevic V, Djordjevic PB, Lalic K, et al. Parameters of antioxidative defense in type 2 diabetic patients with cardiovascular complications. Ann Med. 2005; 37: 613-20, CrossRef.
Valgimigli M, Rigolin GM, Fucili A, Porta MD, Soukhomovskaia O, Malagutti P, et al. CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation. 2004; 110: 1209-12, CrossRef.
Haendeler J, Dimmeler S. Inseparably Tied: functional and antioxidative capacity of endothelial progenitor cells. Circ Res. 2006; 98: 157-8, CrossRef.
Schroeter MR, Leifheit M, Sudholt P, Heida NM, Dellas C, Rohm I, et al. Leptin enhances the recruitment of endothelial progenitor cells into neointimal lesions after vascular injury by promoting integrinmediated adhesion. Circ Res. 2008; 103: 536-44, CrossRef.
Hristov M, Zernecke A, Bidzhekov K, Liehn EA, Shagdarsuren E, Ludwig A, et al. Importance of CXC Chemokine Receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res. 2007; 100: 590-7, CrossRef.
Han JK, Lee HS, Yang HM, Hur J, Jun SI, Kim JY, et al. Peroxisome proliferator-activated receptor-δ agonist enhances vasculogenesis by regulating endothelial progenitor cells through genomic and nongenomic activations of phosphatidylinositol 3-kinase/Akt pathway. Circulation. 2008; 118: 1021-33, CrossRef.
Thum T, Tsikas D, Stein S, Schultheiss M, Eigenthaler M, Anker SD, et al. Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. J Am Coll Cardiol. 2005; 46: 1693-701, CrossRef.
Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003; 9: 1370-6, CrossRef.
Sasaki K, Heeschen C, Aicher A, Ziebart T, Honold J, Urbich C, et al. Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy. Proc Natl Acad Sci USA. 2006; 103: 14537-41, CrossRef.
Thum T, Fraccarollo D, Schultheiss M, Froese S, Galuppo P, Widder JD, et al. Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes. 2007; 56: 666-74, CrossRef.
Kissel CK, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol. 2007; 49: 2341-9, CrossRef.
Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007; 3: 640-9, CrossRef.
Sharpless NE, DePinho RA. How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol. 2007; 8: 703-13, CrossRef.
Dimmeler S, Leri A. Aging and disease as modifiers of efficacy of cell therapy. Circ Res. 2008; 102: 1319-30, CrossRef.
Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005; 45: 1449-57, CrossRef.
Jiao C, Fricker S, Schatteman G. The chemokine (C-X-C motif) receptor 4 inhibitor AMD3100 accelerates blood flow restoration in diabetic mice. Diabetologia. 2006; 49: 2786-9, CrossRef.
Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001; 108: 391-7, CrossRef.
Avogaro A, Fadini GP, Gallo A, Pagnin E, de Kreutzenberg S. Endothelial dysfunction in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2006; 16 (Suppl. 1): S39-45, PMID.
Krankel 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. Arterioscler Thromb Vasc Biol. 2005; 25: 698-703, CrossRef.
Seeger FH, Haendeler J, Walter DH, Rochwalsky U, Reinhold J, Urbich C, et al. p38 mitogen-activated protein kinase downregulates endothelial progenitor cells. Circulation. 2005; 111: 1184-91, CrossRef.
Humpert PM, Neuwirth R, Battista MJ, Voronko O, von Eynatten M, Konrade I, et al. SDF-1 genotype influences insulindependent mobilization of adult progenitor cells in type 2 diabetes. Diabetes Care. 2005; 28: 934-6, CrossRef.
Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, et al. Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J. 2006; 27: 2247-55, CrossRef.
Ingram DA, Krier TR, Mead LE, McGuire C, Prater DN, Bhavsar J, et al. Clonogenic endothelial progenitor cells are sensitive to oxidative stress. Stem Cells. 2006; 25: 297-304, CrossRef.
Gadau S, Emanueli C, Van Linthout S, Graiani G, Todaro M, Meloni M, et al. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia. 2006; 49: 405-20, CrossRef.
Marchetti V, Menghini R, Rizza S, Vivanti A, Feccia T, Lauro D, et al. Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling. Diabetes. 2006; 55: 2231-37, CrossRef.
Csaky KG, Baffi JZ, Byrnes GA, Wolfe JD, Hilmer SC, Flippin J, et al. Recruitment of marrow-derived endothelial cells to experimental choroidal neovascularization by local expression of vascular endothelial growth factor. Exp Eye Res. 2004; 78: 1107-16, CrossRef.
Butler JM, Guthrie SM, Koc M, Afzal A, Caballero S, Brooks HL, et al. SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest. 2005; 115: 86-93, CrossRef.
Abaci A, Oguzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation. 1999; 99: 2239-42, CrossRef.
Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003; 26: 2653-64, CrossRef.
Cho HJ, Kim HS, Lee MM, Kim DH, Yang HJ, Hur J, et al. Mobilized endothelial progenitor cells by granulocty-macropahge colony stimulatin factor accelerate reendothelization and reduce vascular inflammation after intravascular radiation. Circulation. 2003; 108: 2918-25, CrossRef.
Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, et al. Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med. 2005; 11: 261-2, CrossRef.
Lee IG, Chae SL, Kim JC. Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of DR. Eye. 2006; 20: 546-52, CrossRef.
Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, et al. Transplantationof progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCAREAMI Trial. J Am Coll Cardiol. 2005; 44: 1690-9, CrossRef.
Duh E, Aiello LP. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes. 1999; 48:1899-906, CrossRef.
Fadini GP, Avogaro A. Autologous transplantation of granulocyte colony–stimulating factor–mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes (Letter). Diabetes Care. 2006; 29: 478-9, CrossRef.
Simo R, Lecube A, Garcia-Arumi J, Carrasco E, Hernandez C. Hepatocyte growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy: its relationship with vascular endothelial growth factor and retinopathy activity. Diabetes Care. 2004; 27: 287-8, CrossRef.
Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, et al. Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes Care. 2002; 25: 2352, CrossRef.
Freyberger H, Brocker M, Yakut H, Hammer J, Effert R, Schifferdecker E, et al. Increased levels of plateletderived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2000; 108: 106-9, CrossRef.
Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN, et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med. 2002; 8: 607-12, CrossRef.
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: 714-6, CrossRef.
Watanabe D, Suzuma K, Matsui S, Kurimoto M, Kiryu J, Kita M, et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med. 2005; 353: 782-92, CrossRef.
Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Duan J, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation. 2001; 103: 897-903, CrossRef.
Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001; 107: 1395-402, CrossRef.
Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001; 98: 10344-9, CrossRef.
Ayach BB, Yoshimitsu M, Dawood F, Sun M, Arab S, Chen M, et al. Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction. Proc Natl Acad Sci USA. 2006; 103: 2304-9, CrossRef.
Ziegelhoeffer T, Fernandez B, Kostin S, Heil M, Voswinckel R, Helisch A, et al. Bone marrow-derived cells do not incorporate into the adult growing vasculature. Circ Res. 2004; 94: 230-8, CrossRef.
Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004; 94: 678-85, CrossRef.
Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, et al. Local delivery of marrow-derived stromal cells augmentscollateral perfusion through paracrine mechanisms. Circulation. 2004; 109: 1543-9, CrossRef.
Ballard VLT, Edelberg JM. Stem cell and the regeneration of the aging cardiovascular system. Circ Res. 2007; 100: 1116-27, CrossRef.
Ballard VL, Edelberg JM. Harnessing hormonal signaling for cardioprotection. Sci Aging Knowledge Environ. 2005; 2005: re6. CrossRef.
Edelberg JM, Tang L, Hattori K, Lyden D, Rafii S. Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res. 2002; 90: e89-93, CrossRef.
Qian HS, de Resende MM, Beausejour C, Huw LY, Liu P, Rubanyi GM, et al. Age-dependent acceleration of ischemic injury in endothelial nitric oxide synthase-deficient mice: potential role of impaired VEGF receptor 2 expression. J Cardiovasc Pharmacol. 2006; 47: 587-93, CrossRef.
Losordo DW, Vale PR, Isner JM. Gene therapy for myocardial angiogenesis. Am Heart J. 1999; 138: S132-41, CrossRef.
Symes JF, Losordo DW, Vale PR, Lathi KG, Esakof DD, Mayskiy M, et al. Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thorac Surg. 1999; 68: 830-6, CrossRef.
Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet. 1996; 348: 370-4, CrossRef.
Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation. 1998; 97: 1114-23, CrossRef.
Xaymardan M, Tang L, Zagreda L, Pallante B, Zheng J, Chazen JL, et al. Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes. Circ Res. 2004; 94: e39-45, CrossRef.
Edelberg JM, Lee SH, Kaur M, Tang L, Feirt NM, McCabe S, et al. Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model: feasibility of restoring impaired angiogenic capacity in the aging heart. Circulation. 2002; 105: 608-13, CrossRef.
Pallante BA, Duignan I, Okin D, Chin A, Bressan MC, Mikawa T, et al. Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms. Circ Res. 2007; 100: e1-11, CrossRef.
Ballard VL, Sharma A, Duignan I, Holm JM, Chin A, Choi R, et al. Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization. FASEB J. 2006; 20: 717-9, CrossRef.
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000; 95 : 952-8, PMID.
Werner N, Priller J, Laufs U, Endres M, Bohm M, Dirnagl U, et al. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Thromb Vasc Biol. 2002; 22: 1567-72, CrossRef.
Spyridopoulos I, Haendeler J, Urbich C, Brummendorf TH, Oh H, Schneider MD, et al. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation. 2004; 110: 3136-42, CrossRef.
Walsh K, Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000; 6: 1004-10, CrossRef.
Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway: Requirement for Flk-1/KDR activation. J Biol Chem. 1998; 273: 30336-43, CrossRef.
Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002; 106: 3009-17, CrossRef.
Waltenberger J. Impaired collateral vessel development in diabetes: potential cellularmechanisms and therapeutic implications. Cardiovasc Res. 2001; 49: 554-60, CrossRef.
Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest. 2000; 106: 571-8, CrossRef.
Awad O, Jiao C, Ma N, Dunnwald M, Schatteman GC. Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors. Stem Cells. 2005; 23: 575-83, CrossRef.
Asai J, Takenaka H, Kusano KF, Ii M, Luedemann C, Curry C, et al. Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cellmediated microvascular remodeling. Circulation. 2006; 113: 2413-24, CrossRef.
Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, et al. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006; 26: 2140-6, CrossRef.
Korbling M, Reuben JM, Gao H, Lee BN, Harris DM, Cogdell D, et al. Recombinant human granulocytecolony-stimulating factor-mobilized and apheresiscollected endothelial progenitor cells: a novel blood cell component for therapeutic vasculogenesis. Transfusion. 2006; 46: 1795-802, CrossRef.
Zbinden S, Zbinden R, Meier P, Windecker S, Seiler C. Safety and efficacy of subcutaneous-only granulocytemacrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease. J Am Coll Cardiol. 2005; 46: 1636-42, CrossRef.
Hill JM, Syed MA, Arai AE, Powell TM, Paul JD, Zalos G, et al. Outcomes and risks of granulocyte colonystimulating factor in patients with coronary artery disease. J Am Coll Cardiol. 2005; 46: 1643-8, CrossRef.
Tamarat R, Silvestre JS, Le Ricousse-Roussanne S, Barateau V, Lecomte-Raclet L, Clergue M, et al. Impairment in ischemia-induced neovascularization in diabetes: bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. Am J Pathol. 2004; 164: 457-66, CrossRef.
Ebrahimian TG, Heymes C, You D, Blanc-Brude O, Mees B, Waeckel L, et al. NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. Am J Pathol. 2006; 169: 719-28, CrossRef.
Rosso A, Balsamo A, Gambino R, Dentelli P, Falcioni R, Cassader M, et al. p53 mediates the accelerated onset of senescence of endothelial progenitor cells in diabetes. J Biol Chem. 2006; 281: 4339-47, CrossRef.
Liew A, Barry F, O’Brien T. Endothelial progenitor cells: diagnostic and therapeutic considerations. Bioessays. 2006; 28: 261-70, CrossRef.
DOI: https://doi.org/10.18585/inabj.v1i2.89
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