© 2001 American Heart Association, Inc.
Integrative Physiology |
Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+AC133+ Endothelial Precursor Cells
From the Division of Hematology and Oncology (M.G., S.D., K.H., M.L.R., S.R.), Cornell University Medical College; W Randolph Burn Center (R.Y., H.H.) and Division of Cardiothoracic Surgery (L.G.), New York Presbyterian Hospital; and Imclone Systems Incorporated (D.H., L.W.), New York, NY.
Correspondence to Shahin Rafii, MD, Division of Hematology/Oncology, Cornell University Medical College, 1300 York Ave, Room C-606, New York, NY 10021. E-mail srafii{at}mail.med.cornell.edu
Abstract—Bone marrow (BM)–derived circulating endothelial precursor cells (CEPs) are thought to play a role in postnatal angiogenesis. Emerging evidence suggests that angiogenic stress of vascular trauma may induce mobilization of CEPs to the peripheral circulation. In this regard, we studied the kinetics of CEP mobilization in two groups of patients who experienced acute vascular insult secondary to burns or coronary artery bypass grafting (CABG). In both burn and CABG patients, there was a consistent, rapid increase in the number of CEPs, determined by their surface expression pattern of vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial cadherin (VE-cadherin), and AC133. Within the first 6 to 12 hours after injury, the percentage of CEPs in the peripheral blood of burn or CABG patients increased almost 50-fold, returning to basal levels within 48 to 72 hours. Mobilized cells also formed late-outgrowth endothelial colonies (CFU-ECs) in culture, indicating that a small, but significant, number of circulating endothelial cells were BM-derived CEPs. In parallel to the mobilization of CEPs, there was also a rapid elevation of VEGF plasma levels. Maximum VEGF levels were detected within 6 to 12 hours of vascular trauma and decreased to baseline levels after 48 to 72 hours. Acute elevation of VEGF in the mice plasma resulted in a similar kinetics of mobilization of VEGFR2+ cells. On the basis of these results, we propose that vascular trauma may induce release of chemokines, such as VEGF, that promotes rapid mobilization of CEPs to the peripheral circulation. Strategies to improve the mobilization and incorporation of CEPs may contribute to the acceleration of vascularization of the injured vascular tissue.
Key Words: circulating endothelial precursor cells\b • mobilization • vascular endothelial growth factor \b • vascular endothelial growth factor receptor 2 • AC133
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M. Hristov, W. Erl, S. Linder, and P. C. Weber Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro Blood, November 1, 2004; 104(9): 2761 - 2766. [Abstract] [Full Text] [PDF]
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I. Rajantie, M. Ilmonen, A. Alminaite, U. Ozerdem, K. Alitalo, and P. Salven Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells Blood, October 1, 2004; 104(7): 2084 - 2086. [Abstract] [Full Text] [PDF]
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M. Valgimigli, G. M. Rigolin, A. Fucili, M. D. Porta, O. Soukhomovskaia, P. Malagutti, A. M. Bugli, L. Z. Bragotti, G. Francolini, E. Mauro, et al. CD34+ and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart Failure Circulation, September 7, 2004; 110(10): 1209 - 1212. [Abstract] [Full Text] [PDF]
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C. Urbich and S. Dimmeler Endothelial Progenitor Cells: Characterization and Role in Vascular Biology Circ. Res., August 20, 2004; 95(4): 343 - 353. [Abstract] [Full Text] [PDF]
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T. Kondo, M. Hayashi, K. Takeshita, Y. Numaguchi, K. Kobayashi, S. Iino, Y. Inden, and T. Murohara Smoking Cessation Rapidly Increases Circulating Progenitor Cells in Peripheral Blood in Chronic Smokers Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1442 - 1447. [Abstract] [Full Text] [PDF]
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J.-H. Choi, K. L. Kim, W. Huh, B. Kim, J. Byun, W. Suh, J. Sung, E.-S. Jeon, H.-Y. Oh, and D.-K. Kim Decreased Number and Impaired Angiogenic Function of Endothelial Progenitor Cells in Patients With Chronic Renal Failure Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1246 - 1252. [Abstract] [Full Text] [PDF]
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J. Rehman, J. Li, L. Parvathaneni, G. Karlsson, V. R. Panchal, C. J. Temm, J. Mahenthiran, and K. L. March Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2314 - 2318. [Abstract] [Full Text] [PDF]
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D. W. Losordo and S. Dimmeler Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease: Part II: Cell-Based Therapies Circulation, June 8, 2004; 109(22): 2692 - 2697. [Full Text] [PDF]
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S Francis Endothelial progenitor cells and coronary artery disease Heart, June 1, 2004; 90(6): 591 - 592. [Abstract] [Full Text] [PDF]
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R. D. Galiano, O. M. Tepper, C. R. Pelo, K. A. Bhatt, M. Callaghan, N. Bastidas, S. Bunting, H. G. Steinmetz, and G. C. Gurtner Topical Vascular Endothelial Growth Factor Accelerates Diabetic Wound Healing through Increased Angiogenesis and by Mobilizing and Recruiting Bone Marrow-Derived Cells Am. J. Pathol., June 1, 2004; 164(6): 1935 - 1947. [Abstract] [Full Text] [PDF]
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T. J. Rabelink, H. C. de Boer, E. J.P. de Koning, and A.-J. van Zonneveld Endothelial Progenitor Cells: More Than an Inflammatory Response? Arterioscler. Thromb. Vasc. Biol., May 1, 2004; 24(5): 834 - 838. [Abstract] [Full Text]
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J. Matsui, T. Wakabayashi, M. Asada, K. Yoshimatsu, and M. Okada Stem Cell Factor/c-kit Signaling Promotes the Survival, Migration, and Capillary Tube Formation of Human Umbilical Vein Endothelial Cells J. Biol. Chem., April 30, 2004; 279(18): 18600 - 18607. [Abstract] [Full Text] [PDF]
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V. Adams, K. Lenk, A. Linke, D. Lenz, S. Erbs, M. Sandri, A. Tarnok, S. Gielen, F. Emmrich, G. Schuler, et al. Increase of Circulating Endothelial Progenitor Cells in Patients with Coronary Artery Disease After Exercise-Induced Ischemia Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 684 - 690. [Abstract] [Full Text] [PDF]
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C.-H. Wang, N. Ciliberti, S.-H. Li, P. E. Szmitko, R. D. Weisel, P. W.M. Fedak, M. Al-Omran, W.-J. Cherng, R.-K. Li, W. L. Stanford, et al. Rosiglitazone Facilitates Angiogenic Progenitor Cell Differentiation Toward Endothelial Lineage: A New Paradigm in Glitazone Pleiotropy Circulation, March 23, 2004; 109(11): 1392 - 1400. [Abstract] [Full Text] [PDF]
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 L. V. Beerepoot, N. Mehra, J. S. P. Vermaat, B. A. Zonnenberg, M. F. G. B. Gebbink, and E. E. Voest Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients Ann. Onc., January 1, 2004; 15(1): 139 - 145. [Abstract] [Full Text] [PDF]
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R. J. Scheubel, H. Zorn, R.-E. Silber, O. Kuss, H. Morawietz, J. Holtz, and A. Simm Age-dependent depression in circulating endothelial progenitor cells inpatients undergoing coronary artery bypass grafting J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2073 - 2080. [Abstract] [Full Text] [PDF]
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S. Dimmeler and M. Vasa-Nicotera Aging of progenitor cells: limitation for regenerative capacity? J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2081 - 2082. [Full Text] [PDF]
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G. Schuch, J. V. Heymach, M. Nomi, M. Machluf, J. Force, A. Atala, J. P. Eder Jr., J. Folkman, and S. Soker Endostatin Inhibits the Vascular Endothelial Growth Factor-Induced Mobilization of Endothelial Progenitor Cells Cancer Res., December 1, 2003; 63(23): 8345 - 8350. [Abstract] [Full Text] [PDF]
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D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis Cardiovasc Res, December 1, 2003; 60(3): 684 - 691. [Abstract] [Full Text] [PDF]
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A. Goette, K. Jentsch-Ullrich, U. Lendeckel, C. Rocken, M. Agbaria, A. Auricchio, M. Mohren, A. Franke, and H. U. Klein Effect of Atrial Fibrillation on Hematopoietic Progenitor Cells: A Novel Pathophysiological Role of the Atrial Natriuretic Peptide? Circulation, November 18, 2003; 108(20): 2446 - 2449. [Abstract] [Full Text] [PDF]
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R. G. Bagley, J. Walter-Yohrling, X. Cao, W. Weber, B. Simons, B. P. Cook, S. D. Chartrand, C. Wang, S. L. Madden, and B. A. Teicher Endothelial Precursor Cells As a Model of Tumor Endothelium: Characterization and Comparison with Mature Endothelial Cells Cancer Res., September 15, 2003; 63(18): 5866 - 5873. [Abstract] [Full Text] [PDF]
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M. Pesce, A. Orlandi, M. G. Iachininoto, S. Straino, A. R. Torella, V. Rizzuti, G. Pompilio, G. Bonanno, G. Scambia, and M. C. Capogrossi Myoendothelial Differentiation of Human Umbilical Cord Blood-Derived Stem Cells in Ischemic Limb Tissues Circ. Res., September 5, 2003; 93 (5): e51 - e62. [Abstract] [Full Text] [PDF]
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G. Bauriedel, A. Jabs, D. Skowasch, R. Hutter, J. J. Badimon, V. Fuster, U. Welsch, and B. Luderitz Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair J. Am. Coll. Cardiol., September 3, 2003; 42(5): 930 - 938. [Abstract] [Full Text] [PDF]
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J. S. Forrester, M. J. Price, and R. R. Makkar Stem Cell Repair of Infarcted Myocardium: An Overview for Clinicians Circulation, September 2, 2003; 108(9): 1139 - 1145. [Full Text] [PDF]
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N. Nagaya, K. Kangawa, M. Kanda, M. Uematsu, T. Horio, N. Fukuyama, J. Hino, M. Harada-Shiba, H. Okumura, Y. Tabata, et al. Hybrid Cell-Gene Therapy for Pulmonary Hypertension Based on Phagocytosing Action of Endothelial Progenitor Cells Circulation, August 19, 2003; 108(7): 889 - 895. [Abstract] [Full Text] [PDF]
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