Investigating the serum irisin level and expression of vascular endothelial growth factor gene and protein in the heart tissue of NMRI mice after resistance training and irisin injection

Document Type : Research Paper

Authors

1 Department of Exercise Physiology, Faculty of Sport Science, University of Isfahan, Isfahan, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran

3 Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Objectives: Angiogenesis plays a vital role in heart function. Irisin is a possible mediator of exercise effects. The aim of the present study was to investigate the serum irisin level and the expression of vascular endothelial growth factor gene and protein in the heart tissue of NMRI mice after resistance training and irisin injection.
Materials and methods: 21 mice (NMRI, 5 weeks old, 18±2 grams) were randomly divided into three groups: control, exercise (resistance training) and irisin. The exercise protocol was implemented for eight weeks. A weight equal to 30% of the mice's weight was attached to their tails, and they climbed a ladder with a height of one meter. The weight gradually increased to twice the weight of the mouse. The irisin group received irisin at a dose of 100 μg/kg/week intraperitoneally for eight weeks. VEGF gene expression in the heart was evaluated using the real-time PCR method, VEGF protein was assessed by immunohistochemistry and western blot, and irisin serum concentration was measured by ELISA.
Findings: In comparison to the control group, the other study groups showed increased expression of VEGF gene and protein, as well as increased serum levels of irisin (P < 0.05). Pearson correlation coefficient demonstrated a significant positive relationship between these parameters within each group (P < 0.05, r > 0).
Conclusion: Irisin probably mediates the relationship between resistance training and angiogenesis in heart tissue.

Keywords

Main Subjects


  1. Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The global burden of cardiovascular diseases and risk: a compass for future health. American College of Cardiology Foundation Washington DC; 2022. p. 2361-71.
  2. Carmeliet P. Angiogenesis in health and disease. Nature medicine. 2003;9(6):653-60.
  3. Buschmann I, Schaper W. Arteriogenesis versus angiogenesis: two mechanisms of vessel growth. Physiology. 1999.
  4. Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies. Genes & cancer. 2011;2(12):1097-105.
  5. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacological reviews. 2004;56(4):549-80.
  6. Farhadi H, Siahkohian M, Lotfali B, Pouran K. Effects of aerobic training and hypoxia on expression angiogenic factors in cardiac male Wistar rats. Journal of Sport in Biomotor Sciences. 2016;2(16):70-9.
  7. Chen H, Chen C, Spanos M, Li G, Lu R, Bei Y, et al. Exercise training maintains cardiovascular health: signaling pathways involved and potential therapeutics. Signal Transduction and Targeted Therapy. 2022;7(1):306.
  8. Zhou X, Xu M, Bryant JL, Ma J, Xu X. Exercise-induced myokine FNDC5/irisin functions in cardiovascular protection and intracerebral retrieval of synaptic plasticity. Cell & bioscience. 2019;9:1-4.
  9. Ho M-Y, Wang C-Y. Role of irisin in myocardial infarction, heart failure, and cardiac hypertrophy. Cells. 2021;10(8):2103.
  10. Aydin S, Kuloglu T, Aydin S, Eren MN, Celik A, Yilmaz M, et al. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides. 2014;52:68-73.
  11. Liao Q, Qu S, Tang L-x, Li L-p, He D-f, Zeng C-y, et al. Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis. Acta Pharmacologica Sinica. 2019;40(10):1314-21.
  12. Pollock ML, Gaesser GA, Butcher J, Després JP, Dishman RK, Franklin BA, et al. ACSM position stand: the recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Journals AZ> Medicine & Science. 1998;30(6).
  13. Kraemer WJ, Ratamess NA, French DN. Resistance training for health and performance. Current sports medicine reports. 2002;1:165-71.
  14. Dehghan F, Zamani S, Barreiro C, Jami MS. Irisin injection mimics exercise effects on the brain proteome. European Journal of Neuroscience. 2021;54(10):7422-41.
  15. Wang Y, Zhang X, Zhou M, Wu Y, Ma Y, Liu J, et al. Irisin pre-treatment promotes multi-territory perforator flap survival in rats: An experimental study. Injury. 2020;51(11):2442-8.
  16. Berra E, Pagès G, Pouysségur J. MAP kinases and hypoxia in the control of VEGF expression. Cancer and Metastasis reviews. 2000;19:139-45.
  17. Ramakrishnan S, Anand V, Roy S. Vascular endothelial growth factor signaling in hypoxia and inflammation. Journal of neuroimmune pharmacology. 2014;9:142-60.
  18. Lee S, Farrar RP. Resistance training induces muscle-specific changes in muscle mass and function in rat. Journal of Exercise physiology online. 2003;6(2).
  19. Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, et al. The myokine irisin increases cortical bone mass. Proceedings of the National Academy of Sciences. 2015;112(39):12157-62.
  20. Shahabi S, Esfarjani F, Reisi J, Momenzadeh S, Jami M-S, Zamani S. The effects of 8-week resistance and endurance trainings on bone strength compared to irisin injection protocol in mice. Advanced Biomedical Research. 2021;10.
  21. Li Q, Guo H, Chou DW, Berndt A, Sundberg JP, Uitto J. Mouse models for pseudoxanthoma elasticum: genetic and dietary modulation of the ectopic mineralization phenotypes. PLoS One. 2014;9(2):e89268.
  22. Rodrigues EA, Lima ARR, Gomes MJ, Souza LM, Pontes THD, Pagan LU, et al. Influence of Isolated Resistance Exercise on Cardiac Remodeling, Myocardial Oxidative Stress, and Metabolism in Infarcted Rats. Antioxidants. 2023;12(4):896.
  23. Xi Y, Hao M, Liang Q, Li Y, Gong D-W, Tian Z. Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A–Smad2/3 in rats following myocardial infarction. Journal of sport and health science. 2021;10(5):594-603.
  24. Kim H-B, Seo M-W, Jung HC, editors. Effects of Aerobic vs. Resistance Exercise on Vascular Function and Vascular Endothelial Growth Factor in Older Women. Healthcare; 2023: MDPI.
  25. Sabaratnam R, Wojtaszewski JF, Højlund K. Factors mediating exercise‐induced organ crosstalk. Acta Physiologica. 2022;234(2):e13766.
  26. Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle. Wiley Online Library; 2003.
  27. Atherton PJ, Babraj JA, Smith K, Singh J, Rennie MJ, Wackerhage H. Selective activation of AMPK‐PGC‐1α or PKB‐TSC2‐mTOR signaling can explain specific adaptive responses to endurance or resistance training‐like electrical muscle stimulation. The FASEB journal. 2005;19(7):1-23.
  28. Rinaldi B, Donniacuo M, Sodano L, Gritti G, Signoriello S, Parretta E, et al. Effects of sildenafil on the gastrocnemius and cardiac muscles of rats in a model of prolonged moderate exercise training. PLoS One. 2013;8(7):e69954.
  29. Lennmyr F. Signal Transduction in Focal Cerebral Ischemia: Experimental Studies on VEGF, MAPK and Src family kinases: Acta Universitatis Upsaliensis; 2002.
  30. Quan J-H, Ismail HAHA, Cha G-H, Jo Y-J, Gao FF, Choi I-W, et al. VEGF production is regulated by the AKT/ERK1/2 signaling pathway and controls the proliferation of toxoplasma gondii in ARPE-19 cells. Frontiers in cellular and infection microbiology. 2020;10:184.
  31. Prasadam I, Zhou Y, Du Z, Chen J, Crawford R, Xiao Y. Osteocyte-induced angiogenesis via VEGF–MAPK-dependent pathways in endothelial cells. Molecular and cellular biochemistry. 2014;386:15-25.
  32. Saponaro C, Malfettone A, Ranieri G, Danza K, Simone G, Paradiso A, et al. VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. PloS one. 2013;8(1):e53070.
  33. Ren F, Wu K, Yang Y, Yang Y, Wang Y, Li J. Dandelion polysaccharide exerts anti-angiogenesis effect on hepatocellular carcinoma by regulating VEGF/HIF-1α expression. Frontiers in Pharmacology. 2020;11:460.
  34. Simonetti O, Lucarini G, Rubini C, Goteri G, Zizzi A, Staibano S, et al. Microvessel density and VEGF, HIF‐1α expression in primary oral melanoma: correlation with prognosis. Oral diseases. 2013;19(6):620-7.
  35. Lee CJ, Nicoll JX. Time Course Evaluation of Mitogen-Activated Protein Kinase Phosphorylation to Resistance Exercise: A Systematic Review. Journal of Strength and Conditioning Research. 2023;37(3):710-25.
  36. Villamil-Parra W, Cristancho-Mejía É, Ramon Torrella J, Mancera-Soto EM. Effects of a physical exercise program on HIF-1α in people with Chronic Obstructive Pulmonary Disease living at high altitude: study protocol for a clinical trial. Trials. 2023;24(1):698.
  37. Ji X, Xu Z, Liu D, Chen Y. Effects of exercise training on neurological recovery, TGF-β1, HIF-1α, and Nogo-NgR signaling pathways after spinal cord injury in rats. Clinics. 2023;78:100236.