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
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(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
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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]
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A. Aicher, A. M. Zeiher, and S. Dimmeler Mobilizing Endothelial Progenitor Cells Hypertension, March 1, 2005; 45(3): 321 - 325. [Abstract] [Full Text] [PDF]
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G. Schatteman Are Circulating CD133+ Cells Biomarkers of Vascular Disease? Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 270 - 271. [Full Text] [PDF]
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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]
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B. M. Prior, H. T. Yang, and R. L. Terjung What makes vessels grow with exercise training? J Appl Physiol, September 1, 2004; 97(3): 1119 - 1128. [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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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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