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


1 Department of Exercise Physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

2 Corresponding Author, Department of Exercise Physiology, Gilan-E-Gharb Branch, Islamic Azad University, Gilan-E-Gharb, Iran

3 Department of Exercise Physiology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.


Introduction: This research aimed to investigate the relationship between HIF1-α and VEGF gene genotypes and changes in aerobic capacity following eight weeks of moderate-intensity endurance training in inactive women.
Methods: Twenty-three inactive women aged 34 to 43 years old were conveniently selected and performed aerobic training for eight weeks and five 30-minute sessions per week with an intensity of 55% to 75% of maximum heart rate. Before and after the training period, aerobic capacity was measured by the Bruce test. A saliva sample was taken and different genotypes of the HIF1-α gene including CC and different genotypes of the VEGF gene including GG, CG, and CC were measured. Statistical methods of Paired t-test and ANOVA were used to observe mean differences in aerobic capacity and the Restriction Fragment Length Polymorphism (RLFP) method was used to check genotypes.
Results: The results of changes in the aerobic capacity of the subjects and investigation of the relationship between the different genotypes of VEGF and HIF1-α genes following eight weeks of moderate-intensity endurance training, the aerobic capacity of CC and CT genotypes of the HIF1-α gene were equal pre and post-intervention (p=0.529). Also, GG, CC, and CG genotypes of the VEGF gene were equal to the CG genotype (p=0·873). The CT genotype of the HIF1-α gene has the most increase, but this increase was not significant.
 Conclusion: Therefore, Eight weeks of moderate-intensity endurance training increases the aerobic capacity of HIF1-a and VEGF gene profiles in inactive obese women, but the changes in aerobic capacity of these gene profiles are not significant.


Main Subjects

  1. World Health Organ Tech Rep Ser. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. 2000.
  2. Ogunbode A, Ajayi I, Ladipo M, Fatiregun A. Obesity: An emerging disease. Niger J Clin Pract [Internet]. 2011;14(4):390.
  3. Vineis P, Avendano-Pabon M, Barros H, Bartley M, Carmeli C, Carra L, et al. Special Report: The Biology of Inequalities in Health: The Lifepath Consortium. Front Public Heal [Internet]. 2020 May 12;8.
  4. Pérusse L, Rankinen T, Hagberg\ JM, Loos RJF, Roth SM, Sarzynski MA, et al. Advances in Exercise, Fitness, and Performance Genomics in 2012. Med Sci Sport Exerc [Internet]. 2013 May;45(5):824–31.
  5. Lundby C, Calbet JAL, Robach P. The response of human skeletal muscle tissue to hypoxia. Cell Mol Life Sci [Internet]. 2009 Nov 10;66(22):3615–23.
  6. Prior SJ, Hagberg JM, Phares DA, Brown MD, Fairfull L, Ferrell RE, et al. Sequence variation in hypoxia-inducible factor 1α ( HIF1A ): association with maximal oxygen consumption. Physiol Genomics [Internet]. 2003 Sep 29;15(1):20–6.
  7. Chilov D, Camenisch G, Kvietikova I, Ziegler U, Gassmann M, Wenger RH. Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. J Cell Sci [Internet]. 1999 Apr 15;112(8):1203–12.
  8. Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, et al. Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovasc Res [Internet]. 2008 May 1;78(2):385–94.
  9. Silva JFR da, Rocha NG, Nóbrega ACL da. Mobilization of endothelial progenitor cells with exercise in healthy individuals: a systematic review. 2012;98(2):182–91.
  10. Dengler VL, Galbraith MD, Espinosa JM. Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol [Internet]. 2014 Jan 7;49(1):1–15.
  11. Hassan AF, Kamal MM. Effect of Exercise Training and Anabolic Androgenic Steroids on Hemodynamics , Glycogen Content , Angiogenesis and Apoptosis of Cardiac Muscle in Adult Male Rats. Int J Health Sci (Qassim) [Internet]. 2013 Jan;7(1):47–60.
  12. Farhadi H, Siahkohian M, Bolboli L, Karimi P. Effects of aerobic training and hypoxia on expression angiogenic factors in cardiac male Wistar rats. J Sport Biomotor Sci. 2015;8(16):70–9. (In Persian).
  13. Boutcher SH, Park Y, Dunn SL, Boutcher YN. The relationship between cardiac autonomic function and maximal oxygen uptake response to high-intensity intermittent-exercise training. J Sports Sci [Internet]. 2013 May;31(9):1024–9.
  14. Hudlicka O, Brown MD. Adaptation of Skeletal Muscle Microvasculature to Increased or Decreased Blood Flow: Role of Shear Stress, Nitric Oxide and Vascular Endothelial Growth Factor. J Vasc Res [Internet]. 2009;46(5):504–12.
  15. Jiang BH, Semenza GL, Bauer C, Marti HH. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol Physiol [Internet]. 1996 Oct 1;271(4):C1172–80.
  16. Gavin TP, Wagner PD. Effect of short-term exercise training on angiogenic growth factor gene responses in rats. J Appl Physiol [Internet]. 2001 Apr 1;90(4):1219–26.
  17. Iemitsu M, Maeda S, Jesmin S, Otsuki T, Miyauchi T. Exercise training improves aging-induced downregulation of VEGF angiogenic signaling cascade in hearts. Am J Physiol Circ Physiol [Internet]. 2006 Sep;291(3):H1290–8.
  18. Duggan C, Xiao L, Wang C-Y, McTiernan A. Effect of a 12-Month Exercise Intervention on Serum Biomarkers of Angiogenesis in Postmenopausal Women: A Randomized Controlled Trial. Cancer Epidemiol Biomarkers Prev [Internet]. 2014 Apr 1;23(4):648–57.
  19. Hamel P, Simoneau JA, Lortie G, Boulay MR, Bouchard C. Heredity and muscle adaptation to endurance training. Med Sci Sports Exerc. 1986;18(6):690–6.
  20. Sarzynski MA, Rankinen T, Sternfeld B, Grove ML, Fornage M, Jacobs DR, et al. Association of Single-Nucleotide Polymorphisms From 17 Candidate Genes With Baseline Symptom-Limited Exercise Test Duration and Decrease in Duration Over 20 Years. Circ Cardiovasc Genet [Internet]. 2010 Dec;3(6):531–8.
  21. Williams CJ, Williams MG, Eynon N, Ashton KJ, Little JP, Wisloff U, et al. Genes to predict VO2max trainability: a systematic review. BMC Genomics [Internet]. 2017 Nov 14;18(S8):831.
  22. Waltenberger J. VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus. Biochem Soc Trans [Internet]. 2009 Dec 1;37(6):1167–70.
  23. Zadro JR, Shirley D, Andrade TB, Scurrah KJ, Bauman A, Ferreira PH. The Beneficial Effects of Physical Activity: Is It Down to Your Genes? A Systematic Review and Meta-Analysis of Twin and Family Studies. Sport Med - Open [Internet]. 2017 Dec 10;3(1):4.
  24. Bassett DR. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sport Exerc [Internet]. 2000 Jan;70.

25.Bouchard C. Genomic predictors of trainability. Exp Physiol [Internet]. 2012 Mar;97(3):347–52.

  1. Mounier R, Pialoux V, Roels B, Thomas C, Millet G, Mercier J, et al. Effect of intermittent hypoxic training on HIF gene expression in human skeletal muscle and leukocytes. Eur J Appl Physiol [Internet]. 2009 Mar 19;105(4):515–24.
  2. Slivka DR, Heesch MWS, Dumke CL, Cuddy JS, Hailes WS, Ruby BC. Human Skeletal Muscle mRNA Response to a Single Hypoxic Exercise Bout. Wilderness Environ Med [Internet]. 2014 Dec;25(4):462–5.
  3. Yaghoob Nezhad F, Verbrugge SAJ, Schönfelder M, Becker L, Hrabě de Angelis M, Wackerhage H. Genes Whose Gain or Loss-of-Function Increases Endurance Performance in Mice: A Systematic Literature Review. Front Physiol [Internet]. 2019 Mar 22;10.
  4. Breier G. Angiogenesis in Embryonic Development—A Review. Placenta [Internet]. 2000 Mar;21:S11–5.
  5. Bouchard C, Blair SN, Church TS, Earnest CP, Hagberg JM, Häkkinen K, et al. Adverse Metabolic Response to Regular Exercise: Is It a Rare or Common Occurrence? Li S, editor. PLoS One [Internet]. 2012 May 30;7(5):e37887.
  6. Brixius K, Schoenberger S, Ladage D, Knigge H, Falkowski G, Hellmich M, et al. Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50-60 years. Br J Sports Med [Internet]. 2007 Jun 4;42(2):126–9.
  7. Timmons JA, Larsson O, Jansson E, Fischer H, Gustafsson T, Greenhaff PL, et al. Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy. FASEB J [Internet]. 2005 May;19(7):750–60.