Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 PhD Student of Health in Disaster and Emergency Situations, Kerman University of Medical Sciences, Kerman, Iran

2 MSc in Exercise Physiology, University of Tehran, Tehran, Iran

3 Associate Professor, Department of Exercise Physiology, University of Tehran, Tehran, Iran

4 . MSc in injuries and corrective exercises, University of Tehran, Tehran, Iran


Mir-210 is pro-angiogenic micro-RNA in endothelial cells that improves angiogenesis process by suppressing (EphrinA3) and increasing the migration of some gene and protein targets (VEGF). In this study, 12 male rats (age: 8 weeks, mean weight: 180±20 g) were selected and randomly divided into control (n=6) and exercise (n=6) groups. High intensity interval training was performed for 4 weeks, 5 days a week including 3 high intervals (4 minutes at 90-100% of VO2max) and 3 low intervals (2 minutes at 50-60% VO2max). Gene expression was calculated by Real time-PCR technique and 2-∆∆CT. Independent t test was used to determine the significance of variables between the groups.The results showed that high intensity interval training significantly changed the increase of gene expression of Mir-210 and VEGF (P=0.005) (P=0.003). Also, the decrease in gene expression of EphrinA3 receptor in the exercise group was significant compared with the control group (P=0.000). Generally, perhaps due to hypoxiawhich happened along with high intensity interval training, increased gene expression of Mir-210 and VEGF improved the pro-angiogenic function of endothelial cells and this adaptation increased angiogenesis in rats.


  1. Bye, Anja, Helge Røsjø, Stian T. Aspenes, Gianluigi Condorelli, Torbjørn Omland, and Ulrik Wisløff. (2013) "Circulating microRNAs and aerobic fitness–the HUNT-Study." PloS one 8, no. 2: e57496.
  2. Baggish, Aaron L., Andrew Hale, Rory B. Weiner, Gregory D. Lewis, David Systrom, Francis Wang, Thomas J. Wang, and Stephen Y. Chan. (2011) "Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training." The Journal of physiology 589, no. 16: 3983-3994.
  3. Burniston, Jatin G. (2009) "Adaptation of the rat cardiac proteome in response to intensity‐controlled endurance exercise." Proteomics 9, no. 1: 106-115.
  4. Carmeliet, Peter. (2003) "Angiogenesis in health and disease." Nature medicine 9, no. 6: 653.
  5. Denham, Joshua, Brendan J. O'Brien, Francine Z. Marques, and Fadi J. Charchar. (2015) "Changes in the leukocyte methylome and its effect on cardiovascular related genes after exercise." Journal of Applied Physiology: jap-00878.
  6. MacLaren, Donald, and James Morton. 2011. "Biochemistry for sport and exercise metabolism". John Wiley & Sons,
  7. Ferrara, Napoleone. (2002) "VEGF and the quest for tumour angiogenesis factors." Nature Reviews Cancer 2, no. 10: 795-803.
  8. Ferrara, Napoleone, and Terri Davis-Smyth. (1997) "The biology of vascular endothelial growth factor." Endocrine reviews 18, no. 1: 4-25.
  9. Gustafsson, T., A. Knutsson, A. Puntschart, L. Kaijser, Sandberg A-C. Nordqvist, C. Sundberg, and E. Jansson. (2002). "Increased expression of vascular endothelial growth factor in human skeletal muscle in response to short-term one-legged exercise training." Pflügers Archiv European Journal of Physiology 444, no. 6: 752-759.
  10. Gustafsson, Thomas, Helene Rundqvist, Jessica Norrbom, Eric Rullman, Eva Jansson, and Carl Johan Sundberg. (2007). "The influence of physical training on the angiopoietin and VEGF-A systems in human skeletal muscle." Journal of Applied Physiology 103, no. 3: 1012-1020.
  11. Ghosh, Goutam, Indira V. Subramanian, Neeta Adhikari, Xiaoxiao Zhang, Hemant P. Joshi, David Basi, Y. S. Chandrashekhar , Hall JL, Roy S, Zeng Y, Ramakrishnan S. (2010). "Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis." The Journal of clinical investigation 120, no. 11: 4141-4154.
  12. Hudlická.Olga, Brown, Margaret D, (2002) "Angiogenesis in skeletal and cardiac muscle."In The New Angiotherapy, pp. 213-248. Humana Press.
  13. Høydal, Morten A., Ulrik Wisløff, Ole J. Kemi, and Øyvind Ellingsen. (2007) "Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training." European Journal of Cardiovascular Prevention & Rehabilitation 14, no. 6: 753-760.
  14. Mounier, Rémi, Vincent Pialoux, Laurent Schmitt, Jean-Paul Richalet, Paul Robach, Jean Coudert, Eric Clottes, and Nicole Fellmann. (2009) "Effects of acute hypoxia tests on blood markers in high-level endurance athletes." European journal of applied physiology 106, no. 5: 713-720.
  15. Mounier, Rémi, Vincent Pialoux, Belle Roels, Claire Thomas, Grégoire Millet, Jacques Mercier, Jean Coudert, Nicole Fellmann, and Eric Clottes. (2009) "Effect of intermittent hypoxic training on HIF gene expression in human skeletal muscle and leukocytes." European journal of applied physiology 105, no. 4: 515.
  16. Neufeld, Gera, Tzafra Cohen, Stela Gengrinovitch, and Zoya Poltorak. (1999) "Vascular endothelial growth factor (VEGF) and its receptors." The FASEB journal 13, no. 1: 9-22.
  17. Olsson, Anna-Karin, Anna Dimberg, Johan Kreuger, and Lena Claesson-Welsh. (2006). "VEGF receptor signalling? In control of vascular function." Nature reviews Molecular cell biology 7, no. 5: 359-371.
  18. Fasanaro, Pasquale, Yuri D'Alessandra, Valeria Di Stefano, Roberta Melchionna, Sveva Romani, Giulio Pompilio, Maurizio C. Capogrossi, and Fabio Martelli. (2008). "MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3." Journal of Biological Chemistry 283, no. 23: 15878-15883.
  19. Suto, Kyoko, Yasuo Yamazaki, Takashi Morita, and Hiroshi Mizuno. (2005). "Crystal structures of novel vascular endothelial growth factors (VEGF) from snake venoms insight into selective VEGF binding to kinase insert domain-containing receptor but not to fms-like tyrosine kinase-1." Journal of Biological Chemistry 280, no. 3: 2126-2131.
  20. Schulze‐Tanzil, G., O. Al‐Sadi, E. Wiegand, W. Ertel, C. Busch, B. Kohl, and T. Pufe. (2011). "The role of pro‐inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights." Scandinavian journal of medicine & science in sports 21, no. 3: 337-351.
  21. Tallquist, Michelle D., Philippe Soriano, and Richard A. Klinghoffer. (1999). "Growth factor signaling pathways in vascular development." Oncogene 18, no. 55: 7917.
  22. Van Craenenbroeck, Amaryllis H., Kristien J. Ledeganck, Katrijn Van Ackeren, Angelika Jürgens, Vicky Y. Hoymans, Erik Fransen, Volker Adams et al. (2016)."Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise." American Journal of Physiology-Heart and Circulatory Physiology 309, no. 12: H2008-H2016.
  23. Wisløff, Ulrik, Jan Pål Loennechen, Geir Falck, Vidar Beisvag, Susan Currie, Godfrey Smith, and Øyvind Ellingsen.(2001)."Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats." Cardiovascular research 50, no. 3: 495-508.
  24. Yamakuchi, Munekazu. (2012). "MicroRNAs in vascular biology." International journal of vascular medicine .Volume 2012, Article ID 794898,13pages.