Circulation. 2001;103:2776-2779
doi: 10.1161/hc2301.092122
doi: 10.1161/hc2301.092122
(Circulation. 2001;103:2776.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction
From the Cardiovascular Research Institute and Department of Internal Medicine III, Kurume University, and the Institute of Molecular Embryology and Genetics, Kumamoto University (Y.O.), Japan.
Correspondence to Toyoaki Murohara, MD, PhD, Cardiovascular Research Institute, Kurume University, 67 Asahi, Kurume, 830-0011 Japan. E-mail toyom{at}med.kurume-u.ac.jp
Background—Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNCCD34+), are mobilized into PB in acute ischemic events in humans.
Methods and Results—Flow cytometry revealed that circulating MNCCD34+ counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNCCD34+ counts (r=0.35, P=0.01).
Conclusions—This is the first clinical demonstration showing that lineage-committed EPCs and MNCCD34+, their putative precursors, are mobilized during an acute ischemic event in humans.
Key Words: angiogenesis • endothelium • stem cells • ischemia
This article has been cited by other articles:
 |
|
 |
|
  A. Surdacki, E. Marewicz, E. Wieteska, G. Szastak, T. Rakowski, E. Wieczorek-Surdacka, D. Dudek, J. Pryjma, and J. S. Dubiel Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2265 - 2273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Muller-Ehmsen, D. Braun, T. Schneider, R. Pfister, N. Worm, K. Wielckens, C. Scheid, P. Frommolt, and M. Flesch Decreased number of circulating progenitor cells in obesity: beneficial effects of weight reduction Eur. Heart J., June 2, 2008; 29(12): 1560 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thill, N. V. Strunnikova, M. J. Berna, N. Gordiyenko, K. Schmid, S. W. Cousins, D. J. S. Thompson, and K. G. Csaky Late Outgrowth Endothelial Progenitor Cells in Patients with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2696 - 2708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Ince, M Valgimigli, M Petzsch, J S. de Lezo, F Kuethe, S Dunkelmann, G Biondi-Zoccai, and C A Nienaber Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis Heart, May 1, 2008; 94(5): 610 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chu, K.-H. Jung, S.-T. Lee, H.-K. Park, D.-I. Sinn, J.-M. Kim, D.-H. Kim, J.-H. Kim, S.-J. Kim, E.-C. Song, et al. Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke * Supplemental Methods Stroke, May 1, 2008; 39(5): 1441 - 1447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zohlnhofer, A. Dibra, T. Koppara, A. de Waha, R. S. Ripa, J. Kastrup, M. Valgimigli, A. Schomig, and A. Kastrati Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor for Myocardial Recovery After Acute Myocardial Infarction: A Meta-Analysis J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1429 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Stein, G. Wessling, I. Deisenhofer, G. Busch, B. Steppich, H. Estner, B. Zrenner, C. Schmitt, S. Braun, A. Schomig, et al. Systemic inflammatory changes after pulmonary vein radiofrequency ablation do not alter stem cell mobilization Europace, April 1, 2008; 10(4): 444 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schlieper, M. Hristov, V. Brandenburg, T. Kruger, R. Westenfeld, A. H. Mahnken, E. Yagmur, G. Boecker, N. Heussen, U. Gladziwa, et al. Predictors of low circulating endothelial progenitor cell numbers in haemodialysis patients Nephrol. Dial. Transplant., March 19, 2008; (2008) gfn103v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 217 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W Wojakowski, M Kucia, M Kazmierski, M Z Ratajczak, and M Tendera Circulating progenitor cells in stable coronary heart disease and acute coronary syndromes: relevant reparatory mechanism? Heart, January 1, 2008; 94(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brunner, H. D. Theiss, A. Murr, T. Negele, and W.-M. Franz Primary hyperparathyroidism is associated with increased circulating bone marrow-derived progenitor cells Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1670 - E1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tongers and D. W. Losordo Frontiers in Nephrology: The Evolving Therapeutic Applications of Endothelial Progenitor Cells J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2843 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Denny, S. Thacker, H. Mehta, E. C. Somers, T. Dodick, F. J. Barrat, W. J. McCune, and M. J. Kaplan Interferon-{alpha} promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis Blood, October 15, 2007; 110(8): 2907 - 2915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Werner, C. H. Kamani, C. Gensch, M. Bohm, and U. Laufs The Peroxisome Proliferator Activated Receptor-{gamma} Agonist Pioglitazone Increases Number and Function of Endothelial Progenitor Cells in Patients With Coronary Artery Disease and Normal Glucose Tolerance Diabetes, October 1, 2007; 56(10): 2609 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shmilovich, V. Deutsch, A. Roth, H. Miller, G. Keren, and J. George Circulating endothelial progenitor cells in patients with cardiac syndrome X Heart, September 1, 2007; 93(9): 1071 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Michowitz, E. Goldstein, D. Wexler, D. Sheps, G. Keren, and J. George Circulating endothelial progenitor cells and clinical outcome in patients with congestive heart failure Heart, September 1, 2007; 93(9): 1046 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ferrario, M. Massa, V. Rosti, R. Campanelli, M. Ferlini, B. Marinoni, G. M. De Ferrari, V. Meli, M. De Amici, A. Repetto, et al. Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction Eur. Heart J., August 1, 2007; 28(15): 1805 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Grote, G. Salguero, M. Ballmaier, M. Dangers, H. Drexler, and B. Schieffer The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration Blood, August 1, 2007; 110(3): 877 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schmidt, K. Brixius, and W. Bloch Endothelial Precursor Cell Migration During Vasculogenesis Circ. Res., July 20, 2007; 101(2): 125 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Oh, J.-M. Ha, E. O, B. H. Lee, S. K. Lee, B.-S. Shim, Y.-K. Hong, and Y. A. Joe Tumor Angiogenesis Promoted by Ex vivo Differentiated Endothelial Progenitor Cells Is Effectively Inhibited by an Angiogenesis Inhibitor, TK1-2 Cancer Res., May 15, 2007; 67(10): 4851 - 4859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Theiss, R. David, M. G. Engelmann, A. Barth, K. Schotten, M. Naebauer, B. Reichart, G. Steinbeck, and W.-M. Franz Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM) Eur. Heart J., May 2, 2007; 28(10): 1258 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schwartzenberg, V. Deutsch, S. Maysel-Auslender, S. Kissil, G. Keren, and J. George Circulating Apoptotic Progenitor Cells: A Novel Biomarker in Patients With Acute Coronary Syndromes Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): e27 - e31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Murphy, G. S. Kanaganayagam, B. Jiang, P. J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A. M. Shah, M. S. Marber, and M. T. Kearney Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 936 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Inoue, M. Sata, Y. Hikichi, R. Sohma, D. Fukuda, T. Uchida, M. Shimizu, H. Komoda, and K. Node Mobilization of CD34-Positive Bone Marrow-Derived Cells After Coronary Stent Implantation: Impact on Restenosis Circulation, February 6, 2007; 115(5): 553 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Roberts, Q. Xiao, G. Weir, Q. Xu, and M. Jahangiri Endothelial Progenitor Cells are Mobilized After Cardiac Surgery Ann. Thorac. Surg., February 1, 2007; 83(2): 598 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aicher, C. Heeschen, K.-i. Sasaki, C. Urbich, A. M. Zeiher, and S. Dimmeler 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, December 19, 2006; 114(25): 2823 - 2830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lipsic, R. G. Schoemaker, P. van der Meer, A. A. Voors, D. J. van Veldhuisen, and W. H. van Gilst Protective Effects of Erythropoietin in Cardiac Ischemia: From Bench to Bedside J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2161 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Lemoli, L. Catani, S. Talarico, E. Loggi, A. Gramenzi, U. Baccarani, M. Fogli, G. L. Grazi, M. Aluigi, G. Marzocchi, et al. Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection Stem Cells, December 1, 2006; 24(12): 2817 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zohlnhofer, I. Ott, A. Kastrati, and A. Schomig Granulocyte Colony-Stimulating Factor and Acute Myocardial Infarction--Reply JAMA, October 25, 2006; 296(16): 1968 - 1969. [Full Text] [PDF]
|
|
|
|
|
|
C. J. Boos, G. Y.H. Lip, and A. D. Blann Circulating Endothelial Cells in Cardiovascular Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Leor and M. Marber Endothelial Progenitors: A New Tower of Babel? J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1588 - 1590. [Full Text] [PDF]
|
|
|
|
|
|
B. J. Capoccia, R. M. Shepherd, and D. C. Link G-CSF and AMD3100 mobilize monocytes into the blood that stimulate angiogenesis in vivo through a paracrine mechanism Blood, October 1, 2006; 108(7): 2438 - 2445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wang, N. Anderson, S.-H. Li, P. E. Szmitko, W.-J. Cherng, P. W.M. Fedak, S. Fazel, R.-K. Li, T. M. Yau, R. D. Weisel, et al. Stem Cell Factor Deficiency Is Vasculoprotective: Unraveling a New Therapeutic Potential of Imatinib Mesylate Circ. Res., September 15, 2006; 99(6): 617 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takaoka, S. Uemura, H. Kawata, K.-i. Imagawa, Y. Takeda, K. Nakatani, N. Naya, M. Horii, S. Yamano, Y. Miyamoto, et al. Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2083 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hirata, T. Minamino, H. Asanuma, M. Fujita, M. Wakeno, M. Myoishi, O. Tsukamoto, K.-i. Okada, H. Koyama, K. Komamura, et al. Erythropoietin Enhances Neovascularization of Ischemic Myocardium and Improves Left Ventricular Dysfunction After Myocardial Infarction in Dogs J. Am. Coll. Cardiol., July 4, 2006; 48(1): 176 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mieno, B. Ramlawi, M. Boodhwani, R. T. Clements, K. Minamimura, T. Maki, S.-H. Xu, C. Bianchi, J. Li, and F. W. Sellke Role of Stromal-Derived Factor-1{alpha} in the Induction of Circulating CD34+CXCR4+ Progenitor Cells After Cardiac Surgery. Circulation, July 4, 2006; 114(1 Suppl): 186 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Numaguchi, T. Sone, K. Okumura, M. Ishii, Y. Morita, R. Kubota, K. Yokouchi, H. Imai, M. Harada, H. Osanai, et al. The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction Circulation, July 4, 2006; 114(1_suppl): I-114 - I-119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. DiFabio, G. R. Thomas, L. Zucco, M. A. Kuliszewski, B. M. Bennett, M. J. Kutryk, and J. D. Parker Nitroglycerin Attenuates Human Endothelial Progenitor Cell Differentiation, Function, and Survival J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 117 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Li, E. E. Sharpe, A. B. Maupin, A. A. Teleron, A. L. Pyle, P. Carmeliet, and P. P. Young VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization FASEB J, July 1, 2006; 20(9): 1495 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y Wang, H E Johnsen, S Mortensen, L Bindslev, R Sejersten Ripa, M Haack-Sorensen, E Jorgensen, W Fang, and J Kastrup Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention Heart, June 1, 2006; 92(6): 768 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. d. S. Meirelles, P. C. Chagastelles, and N. B. Nardi Mesenchymal stem cells reside in virtually all post-natal organs and tissues J. Cell Sci., June 1, 2006; 119(11): 2204 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Blindt, F. Vogt, I. Astafieva, C. Fach, M. Hristov, N. Krott, B. Seitz, A. Kapurniotu, C. Kwok, M. Dewor, et al. A Novel Drug-Eluting Stent Coated With an Integrin-Binding Cyclic Arg-Gly-Asp Peptide Inhibits Neointimal Hyperplasia by Recruiting Endothelial Progenitor Cells J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1786 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Atluri, G. P. Liao, C. M. Panlilio, V. M. Hsu, M. J. Leskowitz, K. J. Morine, J. E. Cohen, M. F. Berry, E. E. Suarez, D. A. Murphy, et al. Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Ann. Thorac. Surg., May 1, 2006; 81(5): 1728 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schomig, G. Busch, B. Steppich, D. Sepp, J. Kaufmann, A. Stein, A. Schomig, and I. Ott Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction Eur. Heart J., May 1, 2006; 27(9): 1032 - 1037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wojakowski, M. Z. Ratajczak, and M. Tendera Interleukin-8: more on the mechanisms of progenitor cells mobilization in acute coronary syndromes Eur. Heart J., May 1, 2006; 27(9): 1013 - 1015. [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. de Oliveira, L. H. W. Gowdak, G. Buckberg, J. E. Krieger, and the RESTORE Group Cell biology, MRI and geometry: insight into a microscopic/macroscopic marriage Eur. J. Cardiothorac. Surg., April 1, 2006; 29(Suppl_1): S259 - S265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Thom, V. M. Bhopale, O. C. Velazquez, L. J. Goldstein, L. H. Thom, and D. G. Buerk Stem cell mobilization by hyperbaric oxygen Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1378 - H1386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Iwakura, S. Shastry, C. Luedemann, H. Hamada, A. Kawamoto, R. Kishore, Y. Zhu, G. Qin, M. Silver, T. Thorne, et al. Estradiol Enhances Recovery After Myocardial Infarction by Augmenting Incorporation of Bone Marrow-Derived Endothelial Progenitor Cells Into Sites of Ischemia-Induced Neovascularization via Endothelial Nitric Oxide Synthase-Mediated Activation of Matrix Metalloproteinase-9 Circulation, March 28, 2006; 113(12): 1605 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G.P. Welt and D. W. Losordo Cell Therapy for Acute Myocardial Infarction: Curb Your Enthusiasm? Circulation, March 14, 2006; 113(10): 1272 - 1274. [Full Text] [PDF]
|
|
|
|
|
|
D. Zohlnhofer, I. Ott, J. Mehilli, K. Schomig, F. Michalk, T. Ibrahim, G. Meisetschlager, J. von Wedel, H. Bollwein, M. Seyfarth, et al. Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor in Patients With Acute Myocardial Infarction: A Randomized Controlled Trial JAMA, March 1, 2006; 295(9): 1003 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goette, K. Jentsch-Ullrich, M. Hammwohner, S. Trautmann, A. Franke, H. U. Klein, and A. Auricchio Cardiac uptake of progenitor cells in patients with moderate-to-severe left ventricular failure scheduled for cardiac resynchronization therapy. Europace, March 1, 2006; 8(3): 157 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wojakowski, M. Tendera, A. Zebzda, A. Michalowska, M. Majka, M. Kucia, K. Maslankiewicz, R. Wyderka, M. Krol, A. Ochala, et al. Mobilization of CD34+, CD117+, CXCR4+, c-met+ stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction Eur. Heart J., February 1, 2006; 27(3): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rohde, C. Malischnik, D. Thaler, T. Maierhofer, W. Linkesch, G. Lanzer, C. Guelly, and D. Strunk Blood Monocytes Mimic Endothelial Progenitor Cells Stem Cells, February 1, 2006; 24(2): 357 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Silvestre and B. I. Levy Molecular Basis of Angiopathy in Diabetes Mellitus Circ. Res., January 6, 2006; 98(1): 4 - 6. [Full Text] [PDF]
|
|