Abstract
Endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) seem to play an important role in vessel formation. While EPCs seem to exert their function mainly through a paracrine effect, the OECs can develop into mature endothelial cells and form tubular structures. Exercise is known to increase angiogenic factors that can mobilize EPCs; however, the effect on OECs is not known. We investigated the response to a single session of strenuous exercise on OECs, vascular endothelial growth factor (VEGF) and inflammatory cell levels in the healthy. Eleven healthy subjects performed 1 h of spinning exercise. Blood samples were collected at 1, 6, 24 and 48 h post-exercise for cell culture and biochemical analysis. OEC colonies doubled one hour after the spinning session (baseline 4.5 ± 4.3 vs. 9.0 ± 3.7, P < 0.05). Serum VEGF increased from 194 ± 107 pg/ml at baseline to 224 ± 111 pg/ml after 1 h, p = ns and neutrophilic granulocytes increased from 3.73 ± 1.38 at baseline to 9.08 ± 10.5 at 1 h (P < 0.01). The increased levels of OECs, VEGF and neutrophilic granulocytes declined gradually at the following time points. VEGF levels and neutrophilic granulocytes were highly correlated to OEC levels, r = 0.903 (VEGF) and r = 0.85 (neutrophilic granulocytes), respectively. Strenuous physical activity increases OEC colonies and is correlated to serum VEGF and neutrophilic granulocytes levels. An acute exercise-induced inflammatory response might be responsible for the VEGF release and subsequent increase of OECs. The clinical importance of these findings remains to be elucidated.
Similar content being viewed by others
References
Aicher A, Zeiher AM, Dimmeler S (2005) Mobilizing endothelial progenitor cells. Hypertension 45:321–325
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967
Bahlmann FH, de Groot K, Mueller O, Hertel B, Haller H, Fliser D (2005) Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists. Hypertension 45:526–529
Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE (1999) Exercise training enhances endothelial function in young men. J Am Coll Cardiol 33:1379–1385
George J, Goldstein E, Abashidze S, Deutsch V, Shmilovich H, Finkelstein A, Herz I, Miller H, Keren G (2004) Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation. Eur Heart J 25:1003–1008
Gielen S, Schuler G, Hambrecht R (2001) Exercise training in coronary artery disease and coronary vasomotion. Circulation 103:e1–e6
Gulati R, Jevremovic D, Peterson TE, Chatterjee S, Shah V, Vile RG, Simari RD (2003) Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ Res 93:1023–1025
Gute D, Fraga C, Laughlin MH, Amann JF (1996) Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats. J Appl Physiol 81:619–626
Hambrecht R (1998) Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98:2709–2715
Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N, Schuler G (2000) Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 342(7):454–460
Hambrecht R, Walther C, Möbius-Winkler S, Gielen S, Linke A, Conradi K, Erbs S, Kluge R, Kendziorra K, Sabri O, Sick P, Schuler G (2004) Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease. Circulation 109:1371–1378
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function and cardiovascular risk. N Engl J Med 348:593–600
Hirschi KK, Ingram DA, Yoder MC (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 28:1584–1595
Hoetzer GL, MacEneaney OJ, Irmiger HM, Keith R, Van Guilder GP, Stauffer BL, DeSouza CA (2007) Gender differences in circulating endothelial progenitor cell colony-forming capacity and migratory activity in middle-aged adults. Am J Cardiol 100(3):559–560
Hughes AD, Coady E, Raynor S, Mayet S, Wright AR, Shore AC, Kooner JS, Thom SAMcG, Chaturvedi N (2007) Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis. Eur J Clin Invest 37(1):35–41
Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, Oh BH, Lee MM, Park YB (2004) Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24:288–293
Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 97:3422–3427
Laughlin MH, Joseph B, Wolfe Memorial lecture (2004) Physical activity in prevention and treatment of coronary disease: the battle line is in exercise vascular cell biology. Med Sci Sports Exerc 36:352–362
Lin Y, Weisdorf DJ, Solovey A, Hebbel RP (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71–77
Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T (2001) HMG-CoA reductase inhibitors mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest 108:399–405
Pearson JD (2009) Endothelial progenitor cells—Hype or hope? J Thromb Haemost 7:255–262
Rehman J, Li J, Orschell CM, March KL (2003) Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 107:1164–1169
Rehman J, Li J, Parvathaneni L, Karlsson G, Panchal VR, Temm CJ, Mahenthiran J, March KL (2004) Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol 43:2314–2318
Sandri M, Adams V, Gielen S, Linke A, Lenk K, Kränkel N, Lenz D, Erbs S, Scheinert D, Mohr FW, Schuler G, Hambrecht R (2005) 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 111:3391–3399
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438
Tanaka H, Monahan KD, Seals DR (2001) Age-predicted maximal heart rate revisited. J Am Card 37:153–156
Urbich C, Heeschen C, Aicher A, Dernbach E, Zeiher AZ, Dimmeler S (2003) Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells. Circulation 108:2511–2516
Van Craenenbroeck EMF, Vrints CJ, Haine SE, Vermeulen K, Goovaerts I, Van Tendeloo VFI, Hoymans VY, Conraads VMA (2008) A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile. J Appl Physiol 104:1006–1013
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7
Walther C, Gielen S, Hambrecht R (2004) The effect of exercise training on endothelial function in cardiovascular disease in humans. Exerc Sport Sci Rev 32:129–134
Wang CH, Verma S, Hsieh IC, Chen YJ, Kuo LT, Yang NI, Wang SY, Wu MY, Hsu CM, Cheng CW, Cherng WJ (2006) Enalapril increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system. J Mol Cell Cardiol 41(1):34–43
Wang CH, Cherng WJ, Yang NI, Kuo LT, Hsu CM, Yeh HI, Lan YJ, Yeh CH, Stanford WL (2008) Late-outgrowth endothelial cells attenuate intimal hyperplasia contributed by mesenchymal stem cells after vascular injury. Art Thromb Vasc Biol 28:54
Yeh ET, Zhang S, Körbling M, Wilerson JT, Estrov Z (2003) Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 108:2070–2073
Yip HK, Chang LT, Chang WN, Lu CH, Liou CW, Lan MY, Liu JS, Youssef AA, Chang HW (2008) Level and value of circulating endothelial progenitor cells in patients after acute ischemic stroke. Stroke 39(1):69–74
Yoon CH, Hur J, Park KW, Kim JH, Lee CS, Oh IY, Kim TY, Cho HJ, Kang HJ, Chae IH, Yang HK, Oh BH, Park YB, Kim HS (2005) Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation 112:1618–1627
Acknowledgments
The study was funded by The Western part of Sweden Research Grant. We thank Sverker Jern for valuable scientific input.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Thorell, D., Borjesson, M., Larsson, P. et al. Strenuous exercise increases late outgrowth endothelial cells in healthy subjects. Eur J Appl Physiol 107, 481–488 (2009). https://doi.org/10.1007/s00421-009-1144-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-009-1144-0