Circulation. 2004;109:220-226
Published online before print December 22, 2003, doi: 10.1161/01.CIR.0000109141.48980.37
Published online before print December 22, 2003, doi: 10.1161/01.CIR.0000109141.48980.37
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:220-226.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Physical Training Increases Endothelial Progenitor Cells, Inhibits Neointima Formation, and Enhances Angiogenesis
From Medizinische Klinik und Poliklinik der Universität des Saarlandes (U.L., N.W., A.L., S.W., M.B., G.N.), Innere Medizin III, Homburg, Germany; Klinik und Poliklinik für Neurologie (M.E.), Charité, Humboldt-Universität zu Berlin, Berlin, Germany; and Herz-Kreislauf-Zentrum (K.J., E.M.), Gernsbach, Germany.
Correspondence to Dr Ulrich Laufs, Klinik und Poliklinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg/Saar, Germany. E-mail ulrich{at}laufs.com
Received December 30, 2002; de novo received July 22, 2003; revision received September 12, 2003; accepted September 18, 2003.
Background— The molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood. Bone marrow–derived endothelial progenitor cells (EPCs) are thought to exert beneficial effects on atherosclerosis, angiogenesis, and vascular repair.
Methods and Results— To study the effect of physical activity on the bone marrow, EPCs were quantified by fluorescence-activated cell sorter analysis in mice randomized to running wheels (5.1±0.8 km/d, n=12 to 16 per group) or no running wheel. Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267±19%, 289±22%, and 280±25% of control levels after 7, 14, and 28 days, respectively, accompanied by a similar increase of EPCs in the bone marrow and EPCs expanded from spleen-derived mononuclear cells. eNOS-/- mice and wild-type mice treated with NG-nitro-L-arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity. Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs. Running inhibited neointima formation after carotid artery injury by 22±2%. Neoangiogenesis, as assessed in a subcutaneous disc model, was increased by 41±16% compared with controls. In patients with stable coronary artery disease (n=19), moderate exercise training for 28 days led to a significant increase in circulating EPCs and reduced EPC apoptosis.
Conclusions— Physical activity increases the production and circulating numbers of EPCs via a partially NO-dependent, antiapoptotic effect that could potentially underlie exercise-related beneficial effects on cardiovascular diseases.
Key Words: exercise • cells • nitric oxide • angiogenesis • coronary disease
This article has been cited by other articles:
 |
|
 |
|
  S. Dimmeler and A. Leri Aging and Disease as Modifiers of Efficacy of Cell Therapy Circ. Res., June 6, 2008; 102(11): 1319 - 1330. [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]
|
|
|
|
 |
|
 A. Zampetaki, J. P. Kirton, and Q. Xu Vascular repair by endothelial progenitor cells Cardiovasc Res, June 1, 2008; 78(3): 413 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Custodis, M. Baumhakel, N. Schlimmer, F. List, C. Gensch, M. Bohm, and U. Laufs Heart Rate Reduction by Ivabradine Reduces Oxidative Stress, Improves Endothelial Function, and Prevents Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, May 6, 2008; 117(18): 2377 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Foteinos, Y. Hu, Q. Xiao, B. Metzler, and Q. Xu Rapid Endothelial Turnover in Atherosclerosis-Prone Areas Coincides With Stem Cell Repair in Apolipoprotein E-Deficient Mice Circulation, April 8, 2008; 117(14): 1856 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. F. Van Craenenbroeck, C. J. Vrints, S. E. Haine, K. Vermeulen, I. Goovaerts, V. F. I. Van Tendeloo, V. Y. Hoymans, and V. M. A. Conraads A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile J Appl Physiol, April 1, 2008; 104(4): 1006 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Balestrieri, C. Schiano, F. Felice, A. Casamassimi, A. Balestrieri, L. Milone, L. Servillo, and C. Napoli Effect of Low Doses of Red Wine and Pure Resveratrol on Circulating Endothelial Progenitor Cells J. Biochem., February 1, 2008; 143(2): 179 - 186. [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]
|
|
|
|
|
|
P. Muller, A. Kazakov, A. Semenov, M. Bohm, and U. Laufs Pressure-induced cardiac overload induces upregulation of endothelial and myocardial progenitor cells Cardiovasc Res, January 1, 2008; 77(1): 151 - 159. [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]
|
|
|
|
 |
|
 R. V. Milani and C. J. Lavie The role of exercise training in peripheral arterial disease Vascular Medicine, November 1, 2007; 12(4): 351 - 358. [Abstract] [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]
|
|
|
|
 |
|
 L. W. Jones, M. J. Haykowsky, J. J. Swartz, P. S. Douglas, and J. R. Mackey Early Breast Cancer Therapy and Cardiovascular Injury J. Am. Coll. Cardiol., October 9, 2007; 50(15): 1435 - 1441. [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]
|
|
|
|
|
|
F. Suhr, K. Brixius, M. de Marees, B. Bolck, H. Kleinoder, S. Achtzehn, W. Bloch, and J. Mester Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans J Appl Physiol, August 1, 2007; 103(2): 474 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Leosco, G. Rengo, G. Iaccarino, E. Sanzari, L. Golino, G. D. Lisa, C. Zincarelli, F. Fortunato, M. Ciccarelli, V. Cimini, et al. Prior Exercise Improves Age-Dependent Vascular Endothelial Growth Factor Downregulation and Angiogenesis Responses to Hind-Limb Ischemia in Old Rats J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2007; 62(5): 471 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Fadini, S. Sartore, C. Agostini, and A. Avogaro Significance of Endothelial Progenitor Cells in Subjects With Diabetes Diabetes Care, May 1, 2007; 30(5): 1305 - 1313. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Balasubramaniam, C. F. Mervis, A. M. Maxey, N. E. Markham, and S. H. Abman Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: implications for the pathogenesis of bronchopulmonary dysplasia Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1073 - L1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, S. Hoeber, S. Froese, I. Klink, D. O. Stichtenoth, P. Galuppo, M. Jakob, D. Tsikas, S. D. Anker, P. A. Poole-Wilson, et al. Age-Dependent Impairment of Endothelial Progenitor Cells Is Corrected by Growth Hormone Mediated Increase of Insulin-Like Growth Factor-1 Circ. Res., February 16, 2007; 100(3): 434 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhu, X. Liu, Y. Li, P. J. Goldschmidt-Clermont, and C. Dong Aging in the Atherosclerosis Milieu May Accelerate the Consumption of Bone Marrow Endothelial Progenitor Cells Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 113 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Faraci Protecting the Brain With eNOS: Run for Your Life Circ. Res., November 10, 2006; 99(10): 1029 - 1030. [Full Text] [PDF]
|
|
|
|
|
|
K. Gertz, J. Priller, G. Kronenberg, K. B. Fink, B. Winter, H. Schrock, S. Ji, M. Milosevic, C. Harms, M. Bohm, et al. Physical Activity Improves Long-Term Stroke Outcome via Endothelial Nitric Oxide Synthase-Dependent Augmentation of Neovascularization and Cerebral Blood Flow Circ. Res., November 10, 2006; 99(10): 1132 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Meyer, G. Kundt, U. Lenschow, P. Schuff-Werner, and W. Kienast Improvement of Early Vascular Changes and Cardiovascular Risk Factors in Obese Children After a Six-Month Exercise Program J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1865 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Shaffer, S. Greene, A. Arshi, G. Supple, A. Bantly, J. S Moores, M. S Parmacek, and E. R Mohler III Effect of acute exercise on endothelial progenitor cells in patients with peripheral arterial disease Vascular Medicine, November 1, 2006; 11(4): 219 - 226. [Abstract] [PDF]
|
|
|
|
 |
|
 V. Fontaine, C. Filipe, N. Werner, P. Gourdy, A. Billon, B. Garmy-Susini, L. Brouchet, F. Bayard, H. Prats, T. Doetschman, et al. Essential Role of Bone Marrow Fibroblast Growth Factor-2 in the Effect of Estradiol on Reendothelialization and Endothelial Progenitor Cell Mobilization Am. J. Pathol., November 1, 2006; 169(5): 1855 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Guven, R. M. Shepherd, R. G. Bach, B. J. Capoccia, and D. C. Link The Number of Endothelial Progenitor Cell Colonies in the Blood Is Increased in Patients With Angiographically Significant Coronary Artery Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1579 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wassmann, N. Werner, T. Czech, and G. Nickenig Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells Circ. Res., October 13, 2006; 99(8): E74 - E83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baumhakel, N. Werner, M. Bohm, and G. Nickenig Circulating endothelial progenitor cells correlate with erectile function in patients with coronary heart disease Eur. Heart J., September 2, 2006; 27(18): 2184 - 2188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Marumo, H. Uchimura, M. Hayashi, K. Hishikawa, and T. Fujita Aldosterone Impairs Bone Marrow-Derived Progenitor Cell Formation Hypertension, September 1, 2006; 48(3): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Petersen, F. Wiesmann, L. E. Hudsmith, M. D. Robson, J. M. Francis, J. B. Selvanayagam, S. Neubauer, and K. M. Channon Functional and Structural Vascular Remodeling in Elite Rowers Assessed by Cardiovascular Magnetic Resonance J. Am. Coll. Cardiol., August 15, 2006; 48(4): 790 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Dome, J. Timar, J. Dobos, L. Meszaros, E. Raso, S. Paku, I. Kenessey, G. Ostoros, M. Magyar, A. Ladanyi, et al. Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res., July 15, 2006; 66(14): 7341 - 7347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. De Bono, D. Adlam, D. J. Paterson, and K. M. Channon Novel quantitative phenotypes of exercise training in mouse models Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R926 - R934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ii, H. Takenaka, J. Asai, K. Ibusuki, Y. Mizukami, K. Maruyama, Y.-s. Yoon, A. Wecker, C. Luedemann, E. Eaton, et al. Endothelial Progenitor Thrombospondin-1 Mediates Diabetes-Induced Delay in Reendothelialization Following Arterial Injury Circ. Res., March 17, 2006; 98(5): 697 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Palange, U. Testa, A. Huertas, L. Calabro, R. Antonucci, E. Petrucci, E. Pelosi, L. Pasquini, A. Satta, G. Morici, et al. Circulating haemopoietic and endothelial progenitor cells are decreased in COPD. Eur. Respir. J., March 1, 2006; 27(3): 529 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Friedrich, K. Walenta, J. Scharlau, G. Nickenig, and N. Werner CD34-/CD133+/VEGFR-2+ Endothelial Progenitor Cell Subpopulation With Potent Vasoregenerative Capacities Circ. Res., February 17, 2006; 98(3): e20 - e25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler and S. Dimmeler Inseparably Tied: Functional and Antioxidative Capacity of Endothelial Progenitor Cells Circ. Res., February 3, 2006; 98(2): 157 - 158. [Full Text] [PDF]
|
|
|
|
|
|
N. F. Voelkel, R. W. Vandivier, and R. M. Tuder Vascular endothelial growth factor in the lung Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L209 - L221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Werner and G. Nickenig Influence of Cardiovascular Risk Factors on Endothelial Progenitor Cells: Limitations for Therapy? Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 257 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Godecke On the impact of NO-globin interactions in the cardiovascular system Cardiovasc Res, February 1, 2006; 69(2): 309 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum, D. Tsikas, S. Stein, M. Schultheiss, M. Eigenthaler, S. D. Anker, P. A. Poole-Wilson, G. Ertl, and J. Bauersachs Suppression of Endothelial Progenitor Cells in Human Coronary Artery Disease by the Endogenous Nitric Oxide Synthase Inhibitor Asymmetric Dimethylarginine J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1693 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, A. Zhang, D.E. Kohan, R.D. Nelson, F.J. Gonzales, T. Yang, C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, et al. Edema and Congestive Heart Failure from Thiazolidone Insulin Sensitizers--Excess Sodium Reabsoption in the Collecting Duct: Collecting Duct-Specific Deletion of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Thiazolidinedione-Induced Fluid Retention. Proc Nat Acad Sci U S A 102: 9406-9411, 2005 J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3139 - 3142. [Full Text] [PDF]
|
|
|
|
|
|
G. Morici, D. Zangla, A. Santoro, E. Pelosi, E. Petrucci, M. Gioia, A. Bonanno, M. Profita, V. Bellia, U. Testa, et al. Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1496 - R1503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Werner, S. Kosiol, T. Schiegl, P. Ahlers, K. Walenta, A. Link, M. Bohm, and G. Nickenig Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes N. Engl. J. Med., September 8, 2005; 353(10): 999 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rosenzweig Circulating Endothelial Progenitors -- Cells as Biomarkers N. Engl. J. Med., September 8, 2005; 353(10): 1055 - 1057. [Full Text] [PDF]
|
|
|
|
|
|
G. Kojda and R. Hambrecht Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc Res, August 1, 2005; 67(2): 187 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sandri, V. Adams, S. Gielen, A. Linke, K. Lenk, N. Krankel, D. Lenz, S. Erbs, D. Scheinert, F. W. Mohr, 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, June 28, 2005; 111(25): 3391 - 3399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schmidt-Lucke, L. Rossig, S. Fichtlscherer, M. Vasa, M. Britten, U. Kamper, S. Dimmeler, and A. M. Zeiher Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events: Proof of Concept for the Clinical Importance of Endogenous Vascular Repair Circulation, June 7, 2005; 111(22): 2981 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Leon Jr, N. Labropoulos, P. Lebda, and P. G. Kalman The Vascular Surgeon's Role in Risk Factor Modification: Results of a Survey Perspectives in Vascular Surgery and Endovascular Therapy, June 1, 2005; 17(2): 145 - 153. [Abstract] [PDF]
|
|
|
|
|
|
N. Krankel, V. Adams, A. Linke, S. Gielen, S. Erbs, K. Lenk, G. Schuler, and R. Hambrecht Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 698 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Friedrich and M. Bohm Human umbilical cord blood cells and myocardial infarction: Novel ways to treat an old problem Cardiovasc Res, April 1, 2005; 66(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
H. Uchimura, T. Marumo, O. Takase, H. Kawachi, F. Shimizu, M. Hayashi, T. Saruta, K. Hishikawa, and T. Fujita Intrarenal Injection of Bone Marrow-Derived Angiogenic Cells Reduces Endothelial Injury and Mesangial Cell Activation in Experimental Glomerulonephritis J. Am. Soc. Nephrol., April 1, 2005; 16(4): 997 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aicher, A. M. Zeiher, and S. Dimmeler Mobilizing Endothelial Progenitor Cells Hypertension, March 1, 2005; 45(3): 321 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schatteman Are Circulating CD133+ Cells Biomarkers of Vascular Disease? Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 270 - 271. [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Futterman and L. Lemberg Cardiac Repair With Autologous Bone Marrow Stem Cells Am. J. Crit. Care., November 1, 2004; 13(6): 512 - 518. [Full Text] [PDF]
|
|
|
|
|
|
M. Abedin, Y. Tintut, and L. L. Demer Mesenchymal Stem Cells and the Artery Wall Circ. Res., October 1, 2004; 95(7): 671 - 676. [Abstract] [Full Text] [PDF]
|
|
|