Effect of acute exercise on vascular endothelial growth factor in adults: a systematic review with meta-analysis

Document Type : review article

Authors

Department of Physical Education and Sports Sciences, Faculty of Humanities, University of Kashan, Kashan, Iran

Abstract

Background and Purpose: Vascular endothelial growth factor (VEGF) is the most important marker of angiogenesis that may increase in response to exercise. However, the effect of acute exercise on this marker has been reported inconsistently. Therefore, the aim of this systematic review and meta-analysis is to investigate the effect of acute exercise on circulating VEGF in adults.
Materials and Methods: In order to extract original articles, a comprehensive search was conducted in the databases of PubMed, Scopus, Web of Science, SID, Magiran and Google Scholar until 2023 March 1 for studies investigating the effects of acute exercise on circulating levels of VEGF. The meta-analysis criteria included studies published in Persian and English language journals, studies with human subjects with an average age of more than 18 years, studies investigating the effect of acute exercise, and studies measuring serum or plasma VEGF levels. To determine the effect size, standardized mean differences (SMD) values and 95% confidence intervals (CIs) were calculated using CMA2 software. The level of heterogeneity was assessed using the I2 test and the publication bias was also assessed with Egger's test.  Furthermore, subgroup analysis was performed for health status (with chronic disease and healthy) and type of exercise (aerobic, resistance and high-intensity interval exercise).
Results: In total, 27 articles (49 exercise interventions) including 704 subjects were included in the meta-analysis. The results of data analysis showed that acute exercise did not lead to significant changes in VEGF immediately after exercise compared to baseline [0.17, (CI: -0.05 to 0.40, p=0.14). The results of subgroup analysis based on the health status showed that exercise had no significant effect on VEGF in healthy subjects [SMD: 0.10, p=0.40], while it tended to increase VEGF in patients [SMD: 0.30, p=0.05]. The results of the subgroup analysis based on the type of exercise also showed that resistance exercise [SMD: 0.58, p=0.008] leads to a significant increase and high-intensity interval exercise [SMD: 0.29, p=0.06] leads to a non-significant increase in VEGF, while the effect of aerobic exercise [SMD: 0.009, p=0.95] was not significant.
Conclusion: In general, the findings of this meta-analysis showed that the type of exercise plays an effective role in the responses of VEGF to acute exercise. Resistance and high intensity interval exercise may lead to an increase in circulating VEGF immediately post exercise, while aerobic exercise does not have significant effects. In addition, exercise may increase VEGF in people with metabolic-cardiovascular disease, whereas, it is not effective in healthy individuals.
 

Keywords

Main Subjects


  1. Taheri Chadorneshin H, Nourshahi M, Ranjbar K. The response of vascular endothelial growth factor to exhausted submaximal exercise and its relationship with VO2max. Journal of Sport Biosciences. 2010;2(7):59-75. [In Persian]
  2. Egginton S. Invited review: activity-induced angiogenesis. Pflügers Archiv-European Journal of Physiology. 2009;457:963-77.
  3. Rezaei R, Nasoohi S, Haghparast A, Khodagholi F, Bigdeli MR, Nourshahi M. High intensity exercise preconditioning provides differential protection against brain injury following experimental stroke. Life sciences. 2018;207:30-5.
  4. Nourshahi M, Ahmadizad S, imani f, Dehghan P. The effect of concentric-concentric isokinetic activity with restricted blood flow on serum VEGF levels in active elderly men. Journal of Sport and Exercise Physiology. 2021;14(1):49-58. [In Persian]
  5. Sabzevari Rad R, Shirvani H, Mahmoodzadeh Hosseini H, Shamsoddini A, Samadi M. Micro RNA-126 promoting angiogenesis in diabetic heart by VEGF/Spred-1/Raf-1 pathway: effects of high-intensity interval training. Journal of Diabetes & Metabolic Disorders. 2020;19:1089-96.
  6. Yeo H-S, Lim J-Y. Effects of different types of exercise training on angiogenic responses in the left ventricular muscle of aged rats. Experimental gerontology. 2022;158:111650.
  7. Wahl P, Jansen F, Achtzehn S, Schmitz T, Bloch W, Mester J, et al. Effects of high intensity training and high volume training on endothelial microparticles and angiogenic growth factors. PLoS One. 2014;9(4):e96024.
  8. Wahl P, Zinner C, Achtzehn S, Behringer M, Bloch W, Mester J. Effects of acid–base balance and high or low intensity exercise on VEGF and bFGF. European journal of applied physiology. 2011;111:1405-13.
  9. Wahl P, Schmidt A, Demarees M, Achtzehn S, Bloch W, Mester J. Responses of angiogenic growth factors to exercise, to hypoxia and to exercise under hypoxic conditions. International journal of sports medicine. 2013;34(02):95-100.
  10. Wahl P, Mathes S, Köhler K, Achtzehn S, Bloch W, Mester J. Effects of active vs. passive recovery during Wingate-based training on the acute hormonal, metabolic and psychological response. Growth hormone & IGF research. 2013;23(6):201-8.
  11. Suhr F, Knuth S, Achtzehn S, Mester J, de Marees M. Acute exhaustive exercise under normoxic and normobaric hypoxic conditions differentially regulates angiogenic biomarkers in humans. Medicina. 2021;57(7):727.
  12. Suhr F, Brixius K, de Marées M, Bölck B, Kleinöder H, Achtzehn S, et al. Effects of short-term vibration and hypoxia during high-intensity cycling exercise on circulating levels of angiogenic regulators in humans. Journal of applied physiology. 2007;103(2):474-83.
  13. Ranjbar K, Nourshahi M, Hedayati M, TAHERI CH. Effect of gender and physical activity on serum vascular endothelial growth factor at rest and response to submaximal exercise. 2011:294-300. [In Persian]
  14. Ribeiro F, Ribeiro IP, Gonçalves AC, Alves AJ, Melo E, Fernandes R, et al. Effects of resistance exercise on endothelial progenitor cell mobilization in women. Scientific Reports. 2017;7(1):1-9.
  15. Nemet D, Hong S, Mills PJ, Ziegler MG, Hill M, Cooper DM. Systemic vs. local cytokine and leukocyte responses to unilateral wrist flexion exercise. Journal of Applied Physiology. 2002;93(2):546-54.
  16. Möbius-Winkler S, Hilberg T, Menzel K, Golla E, Burman A, Schuler G, et al. Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals. Journal of Applied Physiology. 2009;107(6):1943-50.
  17. yadegari m, ravasi aa, Choobineh S. The Responses of Vascular Endothelial Growth Factor and Cortisol Hormone to a Session of High Intensity Interval Training and the Relationship between Their Serum Levels. Journal of Sport Biosciences. 2019;10(4):393-406. [In Persian]
  18. Ravasi AA, Yadegari M, Choobineh S. Comparison of two types of physical activity on response serum VEGF-A, non-athletic men. Journal of Sport Biosciences. 2014;6(1):41-56. [In Persian]
  19. Saidian A, Alizadeh R, Moradi L. Effects of six weeks of aerobic training on the resting levels of VEGF, Body Composition and VO2max within normobaric hypoxic conditions in overweight/obesity women. Journal of Sport and Exercise Physiology. 2021;13(2):3-11. [In Persian]
  20. Li S, Li S, Wang L, Quan H, Yu W, Li T, et al. The effect of blood flow restriction exercise on angiogenesis-related factors in skeletal muscle among healthy adults: A systematic review and meta-analysis. Frontiers in Physiology. 2022;13:814965.
  21. Shibuya M. VEGF-VEGFR signals in health and disease. Biomolecules & therapeutics. 2014;22(1):1.
  22. Khurana R, Simons M, Martin JF, Zachary IC. Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation. 2005;112(12):1813-24.
  23. Hedman M, Hartikainen J, Syvänne M, Stjernvall J, Hedman A, Kivelä A, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation. 2003;107(21):2677-83.
  24. Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, et al. The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation. 2003;107(10):1359-65.
  25. Wewege M, Van Den Berg R, Ward R, Keech A. The effects of high‐intensity interval training vs. moderate‐intensity continuous training on body composition in overweight and obese adults: a systematic review and meta‐analysis. Obesity Reviews. 2017;18(6):635-46.
  26. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. 2008.
  27. Accattato F, Greco M, Pullano SA, Carè I, Fiorillo AS, Pujia A, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PloS one. 2017;12(6):e0178900.
  28. Adams V, Linke A, Breuckmann F, Leineweber K, Erbs S, Kränkel N, et al. Circulating progenitor cells decrease immediately after marathon race in advanced-age marathon runners. European Journal of Preventive Cardiology. 2008;15(5):602-7.
  29. Aidi H, Saghebjoo M, Hedayati M, Ilbeigi S. The response of Serum level of vascular endothelial growth factor of two types of swimming exercise in hypoxic condition in young men. Scientific Journal of Kurdistan University of Medical Sciences. 2015;20(3):10-22. [In Persian]
  30. Baria MR, Miller MM, Borchers J, Desmond S, Onate J, Magnussen R, et al. High Intensity Interval Exercise Increases Platelet and Transforming Growth Factor‐β Yield in Platelet‐Rich Plasma. PM&R. 2020;12(12):1244-50.
  31. Brinkmann C, Schäfer L, Masoud M, Latsch J, Lay D, Bloch W, et al. Effects of cycling and exergaming on neurotrophic factors in elderly type 2 diabetic men–A preliminary investigation. Experimental and Clinical Endocrinology & Diabetes. 2017;125(07):436-40.
  32. Czarkowska-Paczek B, Bartlomiejczyk I, Przybylski J. THE SERUM LEVELS OF GROWTH FACTORS: PDGF, TGF-BETA AND. Journal of physiology and pharmacology. 2006;57(2):189-97.
  33. Danzig V, Mikova B, Kuchynka P, Benakova H, Zima T, Kittnar O, et al. Levels of circulating biomarkers at rest and after exercise in coronary artery disease patients. Physiological research. 2010;59(3(:385-392.
  34. Eken Ö, Kafkas ME. Effects of low and high intensity interval training exercises on VO2max and components of neuromuscular and vascular system in male volunteers. Journal of Musculoskeletal & Neuronal Interactions. 2022;22(3):352.
  35. Gunga H-C, Kirsch K, Beneke R, Böning D, Hopfenmüller W, Leithäuser R, et al. Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels. International journal of sports medicine. 2002;23(07):495-9.
  36. Hall B, Zebrowska A, Kaminski T, Stanula A, Robins A. Effects of hypoxia during continuous and intermittent exercise on glycaemic control and selected markers of vascular function in type 1 diabetes. Experimental and Clinical Endocrinology & Diabetes. 2018;126(04):229-41.
  37. Hamilton B, Tol JL, Knez W, Chalabi H. Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): overlooked biochemical factors that could influence PRP treatment. British journal of sports medicine. 2015;49(14):957-60.
  38. Gu J-W, Gadonski G, Wang J, Makey I, Adair TH. Exercise increases endostatin in circulation of healthy volunteers. BMC physiology. 2004;4:1-6.
  39. Kliszczewicz B, Markert CD, Bechke E, Williamson C, Clemons KN, Snarr RL, et al. Acute effect of popular high-intensity functional training exercise on physiologic markers of growth. The Journal of Strength & Conditioning Research. 2021;35(6):1677-84.
  40. Kraus RM, Stallings III HW, Yeager RC, Gavin TP. Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. Journal of applied physiology. 2004;96(4):1445-50.
  41. Kujach S, Olek RA, Byun K, Suwabe K, Sitek EJ, Ziemann E, et al. Acute sprint interval exercise increases both cognitive functions and peripheral neurotrophic factors in humans: the possible involvement of lactate. Frontiers in neuroscience. 2020;13:1455.
  42. Amaral SL, Linderman JR, Morse MM, Greene AS. Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF. Microcirculation. 2001;8(1):57-67.
  43. Beijer Å, Rosenberger A, Bölck B, Suhr F, Rittweger J, Bloch W. Whole-body vibrations do not elevate the angiogenic stimulus when applied during resistance exercise. PloS one. 2013;8(11):e80143.
  44. Song BX, Azhar L, Koo GKY, Marzolini S, Gallagher D, Swardfager W, et al. The effect of exercise on blood concentrations of angiogenesis markers in older adults: a systematic review and meta-analysis. 2023.
  45. Hedberg M. Myokines in young, healthy subjects: the acute effect on VEGF-A, IL-1ra and IL-10 from a single bout of high intensity interval training. 2022.
  46. 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. Journal of vascular research. 2009;46(5):504-12.
  47. Habibi Maleki A, Tofighi A, Ghaderi Pakdel F, Tolouei Azar J. The effect of 12 weeks of high intensity interval training and high intensity continuous training on vegf, pedf and pai-1 levels of visceral and subcutaneous adipose tissues in rats fed with high fat diet. Sport Physiology & Management Investigations. 2020;12(1):101-20. [In Persian]
  48. Höffner L, Nielsen JJ, Langberg H, Hellsten Y. Exercise but not prostanoids enhance levels of vascular endothelial growth factor and other proliferative agents in human skeletal muscle interstitium. The Journal of physiology. 2003;550(1):217-25.
  49. Ferguson RA, Hunt JE, Lewis MP, Martin NR, Player DJ, Stangier C, et al. The acute angiogenic signalling response to low-load resistance exercise with blood flow restriction. European journal of sport science. 2018;18(3):397-406.
  50. Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y. Exercise, vascular wall and cardiovascular diseases: an update (Part 1). Sports Medicine. 2008;38:1009-24.
  51. Gavin T, Drew J, Kubik C, Pofahl W, Hickner R. Acute resistance exercise increases skeletal muscle angiogenic growth factor expression. Acta physiologica. 2007;191(2):139-46.
  52. Sandri M, Adams V, Gielen S, Linke A, Lenk K, Kränkel N, 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. 2005;111(25):3391-9.
  53. Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001;103(23):2776-9.
  54. Chong AY, Caine GJ, Freestone B, Blann AD, Lip GY. Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure. Journal of the American College of Cardiology. 2004;43(3):423-8.
  55. Khalafi M, Akbari A, Symonds ME, Pourvaghar MJ, Rosenkranz SK, Tabari E. Influence of different modes of exercise training on inflammatory markers in older adults with and without chronic diseases: A systematic review and meta-analysis. Cytokine. 2023;169:156303.
  • Receive Date: 25 July 2023
  • Revise Date: 07 September 2023
  • Accept Date: 17 September 2023
  • First Publish Date: 19 September 2023
  • Publish Date: 22 November 2023