Potential implications of vascular wall resident endothelial progenitor cells

Süleyman Ergün; Derya Tilki; Hans-Peter Hohn; Ursula Gehling; Nerbil Kilic

doi:10.1160/TH07-04-0318

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2007; 98(05): 930-939
DOI: 10.1160/TH07-04-0318

Theme Issue Article

Schattauer GmbH

Potential implications of vascular wall resident endothelial progenitor cells

Süleyman Ergün

¹Institute of Anatomy, University Hospital Essen, Essen, Germany

,

Derya Tilki

²Department of Urology, University Hospital Großhadern, Munich, Germany

,

Hans-Peter Hohn

¹Institute of Anatomy, University Hospital Essen, Essen, Germany

,

Ursula Gehling

³Department of Hepatobiliary and Transplant Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany

,

Nerbil Kilic

⁴Department of Internal Medicine, Hematology/Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

› Institutsangaben

Abstract

Summary

A rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorumlike structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.

Keywords

Postnatal vasculogenesis - angiogenesis - tumor - atherosclerosis - vascular adventitia

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Referenzen

References
1 Carmeliet P. Manipulating angiogenesis in medicine. J Intern Med 2004; 255: 538-561.
2 Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 49: 507-521.
3 Folkman J. Angiogenesis: an organizing principle for drug discovery?. Nat Rev Drug Discov 2007; 6: 273-286.
4 Augustin HG, Breier G. Angiogenesis: molecular mechanisms and functional interactions--2nd Kloster Seeon Meeting of the German Priority Research Grant "Angiogenesis". Thromb Haemost 2003; 89: 190-197.
5 Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-257.
6 Folkman J, Browder T, Palmblad J. Angiogenesis research: guidelines for translation to clinical application. Thromb Haemost 2001; 86: 23-33.
7 Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002; 29: 15-18.
8 Folkman J, Watson K, Ingber D. et al. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989; 339: 58-61.
9 Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-674.
10 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967.
11 Asahara T, Takahashi T, Masuda H. et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999; 18: 3964-3972.
12 Carmeliet P, Luttun A. The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis. Thromb Haemost 2001; 86: 289-297.
13 Kalka C, Asahara T, Krone W. et al. Angiogenesis and vasculogenesis. Therapeutic strategies for stimulation of postnatal neovascularization. Herz 2000; 25: 611-622.
14 Kunz GA, Liang G, Cuculi F. et al. Circulating endothelial progenitor cells predict coronary artery disease severity. Am Heart J 2006; 152: 190-195.
15 Asahara T, Isner JM. Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res 2002; 11: 171-178.
16 Khurana R, Simons M. Endothelial progenitor cells: precursors for angiogenesis. Semin Thorac Cardiovasc Surg 2003; 15: 250-258.
17 Murayama T, Asahara T. Bone marrow-derived endothelial progenitor cells for vascular regeneration. Curr Opin Mol Ther 2002; 4: 395-402.
18 Shi Q, Rafii S, Wu MH. et al. Evidence for circulating bone marrow-derived endothelial cells. Blood 1998; 92: 362-367.
19 Vasa M, Fichtlscherer S, Adler K. et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001; 103: 2885-2890.
20 Aicher A, Rentsch M, Sasaki K. et al. Non bone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res 2007; 100: 581-589.
21 Alessandri G, Girelli M, Taccagni G. et al. Human vasculogenesis ex vivo: embryonal aorta as a tool for isolation of endothelial cell progenitors. Lab Invest 2001; 81: 875-885.
22 Ingram DA, Mead LE, Tanaka H. et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 2004; 104: 2752-2760.
23 Ingram DA, Mead LE, Moore DB. et al. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood 2005; 105: 2783-2786.
24 Invernici G, Emanueli C, Madeddu P. et al. Human fetal aorta contains vascular progenitor cells capable of inducing vasculogenesis, angiogenesis, and myogenesis in vitro and in a murine model of peripheral ischemia. Am J Pathol 2007; 170: 1879-1892.
25 Tavian M, Zheng B, Oberlin E. et al. The vascular wall as a source of stem cells. Ann NY Acad Sci 2005; 1044: 41-50.
26 Zengin E, Chalajour F, Gehling UM. et al. Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development 2006; 133: 1543-1551.
27 Barber CL, Iruela-Arispe ML. The ever-elusive endothelial progenitor cell: identities, functions and clinical implications. Pediatr Res 2006; 59: 26R-32R.
28 Liew A, Barry F, O’Brien T. Endothelial progenitor cells: diagnostic and therapeutic considerations. Bioessays 2006; 28: 261-270.
29 Asahara T, Kawamoto A. Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 2004; 287: C572-C579.
30 Lin EH, Hassan M, Li Y. et al. Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence. Cancer 2007; 110: 534-542.
31 Ribatti D, Nico B, Crivellato E. et al. Endothelial progenitor cells in health and disease. Histol Histopathol 2005; 20: 1351-1358.
32 Tepper OM, Sealove BA, Murayama T. et al. Newly emerging concepts in blood vessel growth: recent discovery of endothelial progenitor cells and their function in tissue regeneration. J Investig Med 2003; 51: 353-359.
33 Bagley RG, Walter-Yohrling J, Cao X. et al. Endothelial precursor cells as a model of tumor endothelium: characterization and comparison with mature endothelial cells. Cancer Res 2003; 63: 5866-5873.
34 Basire A, Sabatier F, Ravet S. et al. High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors. Thromb Haemost 2006; 95: 678-688.
35 Delorme B, Basire A, Gentile C. et al. Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells. Thromb Haemost 2005; 94: 1270-1279.
36 Duan H, Cheng L, Sun X. et al. LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue. Thromb Haemost 2006; 96: 807-815.
37 Gehling UM, Ergun S, Schumacher U. et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 2000; 95: 3106-3112.
38 Heeschen C, Aicher A, Lehmann R. et al. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 2003; 102: 1340-1346.
39 Ishikawa M, Asahara T. Endothelial progenitor cell culture for vascular regeneration. Stem Cells Dev 2004; 13: 344-349.
40 Lev EI, Estrov Z, Aboulfatova K. et al. Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix. Thromb Haemost 2006; 96: 498-504.
41 Redondo S, Hristov M, Gumbel D. et al. Biphasic effect of pioglitazone on isolated human endothelial progenitor cells: involvement of peroxisome proliferator- activated receptor-gamma and transforming growth factor-beta1. Thromb Haemost 2007; 97: 979-987.
42 Yang C, Zhang ZH, Li ZJ. et al. Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation. Thromb Haemost 2004; 91: 1202-1212.
43 Gothert JR, Gustin SE, van Eekelen JA. et al. Genetically tagging endothelial cells in vivo: bone marrowderived cells do not contribute to tumor endothelium. Blood 2004; 104: 1769-1777.
44 Jain RK, Duda DG. Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer Cell 2003; 3: 515-516.
45 Ozerdem U, Alitalo K, Salven P. et al. Contribution of bone marrow-derived pericyte precursor cells to corneal vasculogenesis. Invest Ophthalmol Vis Sci 2005; 46: 3502-3506.
46 Rajantie I, Ilmonen M, Alminaite A. et al. Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells. Blood 2004; 104: 2084-2086.
47 Hattori R, Matsubara H. Therapeutic angiogenesis for severe ischemic heart diseases by autologous bone marrow cells transplantation. Mol Cell Biochem 2004; 264: 151-155.
48 Iwaguro H, Yamaguchi J, Kalka C. et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 2002; 105: 732-738.
49 Schaefer A, Meyer GP, Fuchs M. et al. Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial. Eur Heart J 2006; 27: 929-935.
50 Tateishi-Yuyama E, Matsubara H, Murohara T. 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.
51 Urbich C, Dimmeler S. Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. Kidney Int 2005; 67: 1672-1676.
52 Wollert KC, Meyer GP, Lotz J. et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141-148.
53 Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension 2005; 45: 321-325.
54 Kalka C, Tehrani H, Laudenberg B. et al. VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg 2000; 70: 829-834.
55 Schmidt-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: 2981-2987.
56 Vasa 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. Circ Res 2001; 89: E1-E7.
57 Werner N, Nickenig G. Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy?. Arterioscler Thromb Vasc Biol 2006; 26: 257-266.
58 Dimmeler S, Vasa-Nicotera M. Aging of progenitor cells: limitation for regenerative capacity?. J Am Coll Cardiol 2003; 42: 2081-2082.
59 Hoetzer GL, Van Guilder GP, Irmiger HM. et al. Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. J Appl Physiol 2007; 102: 847-852.
60 Scheubel RJ, Zorn H, Silber RE. et al. Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol 2003; 42: 2073-2080.
61 Beaudry P, Hida Y, Udagawa T. et al. Endothelial progenitor cells contribute to accelerated liver regeneration. J Pediatr Surg 2007; 42: 1190-1198.
62 Hattori K, Dias S, Heissig B. et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 2001; 193: 1005-1014.
63 Lyden D, Hattori K, Dias S. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7: 1194-1201.
64 Takahashi T, Kalka C, Masuda H. et al. Ischemiaand cytokine-induced mobilization of bone marrowderived endothelial progenitor cells for neovascularization. Nat Med 1999; 5: 434-438.
65 Heissig 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: 625-637.
66 Thum T, Fraccarollo D, Galuppo P. et al. Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells. Cardiovasc Res 2006; 70: 50-60.
67 Aicher A, Heeschen C, Sasaki K. et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation 2006; 114: 2823-2830.
68 Goon PK, Boos CJ, Stonelake PS. et al. Circulating endothelial cells in malignant disease. Fut. Oncol 2005; 1: 813-820.
69 Kopp HG, Ramos CA, Rafii S. Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of tumor and ischemic tissue. Curr Opin Hematol 2006; 13: 175-181.
70 Spring H, Schuler T, Arnold B. et al. Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci USA 2005; 102: 18111-18116.
71 Sun B, Zhang S, Ni C. et al. Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow. Stem Cells Dev 2005; 14: 292-298.
72 Arbab AS, Pandit SD, Anderson SA. et al. Magnetic resonance imaging and confocal microscopy studies of magnetically labeled endothelial progenitor cells trafficking to sites of tumor angiogenesis. Stem Cells 2006; 24: 671-678.
73 Dome B, Timar J, Dobos J. et al. Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res 2006; 66: 7341-7347.
74 Li B, Sharpe EE, Maupin AB. 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: 1495-1497.
75 Tamura M, Unno K, Yonezawa S. et al. In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization. Life Sci 2004; 75: 575-584.
76 Folkman J. Angiogenesis and apoptosis. Semin Cancer Biol 2003; 13: 159-167.
77 George J, Afek A, Abashidze A. et al. Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2005; 25: 2636-2641.
78 Simper D, Wang S, Deb A. et al. Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis. Circulation 2003; 108: 143-149.
79 Walter DH, Rittig K, Bahlmann FH. et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow- derived endothelial progenitor cells. Circulation 2002; 105: 3017-3024.
80 Werner N, Nickenig G. Clinical and therapeutical implications of EPC biology in atherosclerosis. J Cell Mol Med 2006; 10: 318-332.
81 Siegel-Axel DI, Gawaz M. Platelets and endothelial cells. Semin Thromb Hemost 2007; 33: 128-135.
82 Blanco-Colio LM, Martin-Ventura JL, Vivanco F. et al. Biology of atherosclerotic plaques: what we are learning from proteomic analysis. Cardiovasc Res 2006; 72: 18-29.
83 Kanter JE, Johansson F, LeBoeuf RC. et al. Do glucose and lipids exert independent effects on atherosclerotic lesion initiation or progression to advanced plaques?. Circ Res 2007; 100: 769-781.
84 Bot I, de Jager SC, Zernecke A. et al. Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice. Circulation 2007; 115: 2516-2525.
85 George J, Goldstein E, Abashidze S. et al. Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation. Eur Heart J 2004; 25: 1003-1008.
86 Lau KK, Chan YH, Yiu KH. et al. Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension. J Hum Hypertens 2007; 21: 445-451.
87 Doyle B, Caplice N. Plaque neovascularization and antiangiogenic therapy for atherosclerosis. J Am Coll Cardiol 2007; 49: 2073-2080.
88 Liu Y, Wilkinson FL, Kirton JP. et al. Hepatocyte growth factor and c-Met expression in pericytes: implications for atherosclerotic plaque development. J Pathol 2007; 212: 12-19.
89 Lucerna M, Zernecke A, de Nooijer R. et al. Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment. Blood 2007; 109: 122-129.
90 Dong C, Goldschmidt-Clermont PJ. Endothelial progenitor cells: a promising therapeutic alternative for cardiovascular disease. J Interv Cardiol 2007; 20: 93-99.
91 Iwase T, Nagaya N, Fujii T. et al. Adrenomedullin enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia. Circulation 2005; 111: 356-362.
92 Kubota Y, Kishi K, Satoh H. et al. Transplanted endothelial progenitor cells augment the survival areas of rat dorsal flaps. Cell Transplant 2003; 12: 647-657.
93 Sakai Y, Kim DK, Iwasa S. et al. Bone marrow chimerism prevents atherosclerosis in arterial walls of mice deficient in apolipoprotein E. Atherosclerosis 2002; 161: 27-34.
94 Fadini GP, Sartore S, Albiero M. et al. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 2006; 26: 2140-2146.
95 Langer H, May AE, Daub K. et al. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circ Res 2006; 98: e2-10.
96 Murasawa S, Llevadot J, Silver M. et al. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation 2002; 106: 1133-1139.
97 Silvestre JS, Gojova A, Brun V. et al. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003; 108: 2839-2842.
98 Moulton KS, Heller E, Konerding MA. et al. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999; 99: 1726-1732.
99 Moulton KS, Vakili K, Zurakowski D. et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA 2003; 100: 4736-4741.
100 Moulton KS, Olsen BR, Sonn S. et al. Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis. Circulation 2004; 110: 1330-1336.
101 Ergun S, Kilic N, Wurmbach JH. et al. Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes. Angiogenesis 2001; 4: 193-206.
102 Schuch G, Heymach JV, Nomi M. et al. Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells. Cancer Res 2003; 63: 8345-8350.
103 Kumamoto M, Nakashima Y, Sueishi K. Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol 1995; 26: 450-456.
104 Kwon HM, Sangiorgi G, Ritman EL. et al. Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. J Clin Invest 1998; 101: 1551-1556.
105 Kwon HM, Sangiorgi G, Ritman EL. et al. Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique. J Am Coll Cardiol 1998; 32: 2072-2079.
106 Michel JB, Thaunat O, Houard X. et al. Topological determinants and consequences of adventitial responses to arterial wall injury. Arterioscler Thromb Vasc Biol 2007; 27: 1259-1268.
107 Langheinrich AC, Michniewicz A, Sedding DG. et al. Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(-/-)/ low-density lipoprotein(-/-) double knockout mice. Arterioscler Thromb Vasc Biol 2006; 26: 347-352.
108 Langheinrich AC, Kampschulte M, Buch T. et al. Vasa vasorum and atherosclerosis -Quidnovi?. Thromb Haemost 2007; 97: 873-879.
109 Khmelewski E, Becker A, Meinertz T. et al. Tissue resident cells play adominant role in arteriogenesis and concomitant macrophage accumulation. Circ Res 2004; 95: E56-E64.
110 Peault B, Oberlin E, Tavian M. Emergence of hematopoietic stem cells in the human embryo. CR Biol 2002; 325: 1021-1026.
111 Peault B, Tavian M. Hematopoietic stem cell emergence in thehuman embryo and fetus. AnnNY Acad Sci 2003; 996: 132-140.
112 Grunewald M, Avraham I, Dor Y. et al. VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 2006; 124: 175-189.
113 Heiss C, Keymel S, Niesler U. et al. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 2005; 45: 1441-1448.
114 Rauscher FM, Goldschmidt-Clermont PJ, Davis BH. et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 2003; 108: 457-463.
115 Zhang W, Zhang G, Jin H. et al. Characteristics of bone marrow-derived endothelialprogenitor cells in aged mice. Biochem Biophys Res Commun 2006; 348: 1018-1023.
116 Galasso G, Schiek of er S Sato K. et al. Impaired angiogenesis in glutathione peroxidase-1-deficient mice is associated with endothelial progenitor cell dysfunction. Circ Res 2006; 98: 254-261.
117 Imanishi T, Hano T, Nishio I. Estrogenreduces angiotensin II-induced acceleration of senescence in endothelial progenitor cells. Hypertens Res 2005; 28: 263-271.
118 Opden BJ, Musters M, Verrips T. et al. Mathematical modeling of vascular endotheliallayer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening. Am J Physiol HeartCircPhysiol 2004; 287: H2651-H2658.
119 Thum T, Fraccarollo D, Thum S. et al. Differential effects of organicnitrates on endothelial progenitor cells are determined by oxidative stress. Arterioscler Thromb Vasc Biol 2007; 27: 748-754.
120 Urbich C, Knau A, Fichtlscherer S. et al. FOXO-dependent expression of theproapoptotic protein Bim: pivotal role for apoptosis signaling in endothelial progenitor cells. FASEB J 2005; 19: 974-976.
121 Yao EH, Yu Y, Fukuda N. Oxidativestress on progenitorand stem cells in cardiovascular diseases. Curr Pharm Biotechnol 2006; 7: 101-108.
122 Imanishi T, Hano T, Nishio I. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidativestress. J Hypertens 2005; 23: 97-104.
123 Ferrara N, Chen H, Davis-Smyth T. et al. Vascular endothelial growth factor is essentialfor corpus luteum angiogenesis. Nat Med 1998; 4: 336-340.
124 Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis?. Cell 1996; 87: 1153-1155.
125 Hanahan D, Folkman J. Patterns and emerging mechanisms of theangiogenic switch during tumori-genesis. Cell 1996; 86: 353-364.
126 Garcia-Barros M, Paris F, Cordon-Cardo C. et al. Tumorresponsetoradiotherapyregulated by endothelialcellapoptosis. Science 2003; 300: 1155-1159.
127 Ruzinova MB, Schoer RA, Gerald W. et al. Effect of angiogenesis inhibition by Idloss and thecontribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 2003; 4: 277-289.
128 Vacca A, Ribatti D. Bonem arrow angiogenesis in multiple myeloma. Leukemia 2006; 20: 193-199.
129 Duda DG, Cohen KS, di Tomaso E. et al. Differential CD146 expression on circulatingversus tissue endothelial cells in rectal cancer patients: implications for circulating endothelialand progenitor cells as biomarkers for antiangiogenic therapy. J Clin Oncol 2006; 24: 1449-1453.
130 Mancuso P, Calleri A, Cassi C. et al. Circulating endothelial cells as a novel marker of angiogenesis. Adv Exp Med Biol 2003; 522: 83-97.
131 Willett CG, Boucher Y, di Tomaso E. et al. Direct evidence that the VEGF-specificantibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004; 10: 145-147.
132 Capillo M, Mancuso P, Gobbi A. et al. Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. Clin Cancer Res 2003; 9: 377-382.
133 Khan ZA, Melero-Martin JM, Wu X. et al. Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin. Blood 2006; 108: 915-921.
134 Alberding JP, Baldwin AL, Barton JK. et al. Onset of pulsatile pressure causes transiently increased filtration through artery wall. Am J Physiol Heart Circ Physiol 2004; 286: H1827-H1835.
135 Gossl M, Malyar NM, Rosol M. et al. Impact of coronaryvasa vasorum functional structure on coronaryvessel wall perfusion distribution. Am J Physiol Heart Circ Physiol 2003; 285: H2019-H2026.
136 Meyer G, Merval R, Tedgui A. Effects of pressure-induced stretch and convection on lowdensity lipoprotein and albumin uptake in the rabbit aortic wall. Circ Res 1996; 79: 532-540.