The Effects of Exercise Training on Vascular Endothelial Growth Factor and Endostatin Gene Expression in Cardiac Tissue of Rats with Type 2 Diabetes Mellitus

Document Type : Original Article (s)

Authors

1 PhD Candidate, Department of Exercise Physiology, School of Sport Sciences, University of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Exercise Physiology, School of Sport Sciences, University of Isfahan, Isfahan, Iran

3 Assistant Professor, Department of Molecular Medicine and Biotechnology, School of Medicine, Arak University of Medical Sciences, Arak, Iran

4 Assistant Professor, Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran

Abstract

Background: Impaired angiogenesis and formation of collateral vessels in skeletal and cardiac muscle, is a major complication of type 2 diabetes mellitus in ischemia. The aim of this study was to evaluate the changes in vascular endothelial grows factor (VEGF) and Endostatin gene expression in cardiac tissue of rats with type 2 diabetes mellitus following aerobic continues and high-intensity interval exercise training.Methods: In this study, 48 Wistar rats were randomly divided into 4 equal groups of healthy control, diabetic control, diabetic continues, and high-intensity interval training. Type 2 diabetes mellitus was induced by intra-peritoneal injection of streptozotocin, and exercise performed 5 sessions per week for 8 weeks. The levels of VEGF and Endostatin gene expression were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method.Findings: There was a significant reduction in the expression of VEGF and Endostatin in the diabetic control group compared to the healthy control group. Compared to the diabetic control group, diabetic continues and high-intensity interval training groups showed a significant increase in expression of VEGF, but there was significant increase in Endostatin expression in diabetic continues group.Conclusion: The results of this study showed that both training methods were effective to increase the expression of VEGF and Endostatin levels after induction of type 2 diabetes mellitus. Since, there was increase in VEGF/Endostatin ratio, increase in pro-angiogenic activity in heart may be occurred, but the high-intensity interval exercise training was more effective to increase the expression of VEGF.

Keywords

References

  1. Bitar MS, Al-Mulla F. Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1alpha-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes. Dis Model Mech 2015; 8(1): 65-80.
  2. Gao Y, Zhao Y, Pan J, Yang L, Huang T, Feng X, et al. Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1/VEGF signaling pathways. Brain Res 2014; 1585: 83-90.
  3. Higashi Y, Murohara T. Therapeutic Angiogenesis. 1st ed. New York, NY: Springer; 2017.
  4. Walia A, Yang JF, Huang YH, Rosenblatt MI, Chang JH, Azar DT. Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications. Biochim Biophys Acta 2015; 1850(12): 2422-38.
  5. Okada M, Oba Y, Yamawaki H. Endostatin stimulates proliferation and migration of adult rat cardiac fibroblasts through PI3K/Akt pathway. Eur J Pharmacol 2015; 750: 20-6.
  6. Smith GA, Fearnley GW, Harrison MA, Tomlinson DC, Wheatcroft SB, Ponnambalam S. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease. J Inherit Metab Dis 2015; 38(4): 753-63.
  7. Punitha IS, Rajendran K, Shirwaikar A, Shirwaikar A. Alcoholic stem extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. Evid Based Complement Alternat Med 2005; 2(3): 375-81.
  8. Afzalpour ME, Chadorneshin HT, Foadoddini M, Eivari HA. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain. Physiol Behav 2015; 147: 78-83.
  9. Hazarika S, Dokun AO, Li Y, Popel AS, Kontos CD, Annex BH. Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circ Res 2007; 101(9): 948-56.
  10. Gao L, Yu DM. Molecular mechanism of limbs' postischemic revascularization improved by perindopril in diabetic rats. Chin Med J (Engl) 2008; 121(21): 2129-33.
  11. Khazaei M, Fallahzadeh AR, Sharifi MR, Afsharmoghaddam N, Javanmard SH, Salehi E. Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats. Clinics (Sao Paulo) 2011; 66(8): 1419-24.
  12. Chou E, Suzuma I, Way KJ, Opland D, Clermont AC, Naruse K, et al. Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue. Circulation 2002; 105(3): 373-9.
  13. Sponder M, Sepiol K, Lankisch S, Priglinger M, Kampf S, Litschauer B, et al. Endostatin and physical exercise in young female and male athletes and controls. Int J Sports Med 2014; 35(13): 1138-42.
  14. Sodha NR, Clements RT, Boodhwani M, Xu SH, Laham RJ, Bianchi C, et al. Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol 2009; 296(2): H428-H434.
  15. Rodrigues B, Jorge L, Mostarda CT, Rosa KT, Medeiros A, Malfitano C, et al. Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction. J Card Fail 2012; 18(9): 734-44.
  16. Erekat NS, Al-Jarrah MD, Al Khatib AJ. Treadmill Exercise Training Improves Vascular Endothelial Growth Factor Expression in the Cardiac Muscle of Type I Diabetic Rats. Cardiol Res 2014; 5(1): 23-9.
  17. Gu JW, Shparago M, Tan W, Bailey AP. Tissue endostatin correlates inversely with capillary network in rat heart and skeletal muscles. Angiogenesis 2006; 9(2): 93-9.
  18. 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 2008; 42(2): 126-9.
  19. Sponder M, Fritzer-Szekeres M, Marculescu R, Litschauer B, Strametz-Juranek J. Physical inactivity increases endostatin and osteopontin in patients with coronary artery disease. Heart Vessels 2016; 31(10): 1603-8.
  20. Nourshahi M, Hedayati M, Nemati J, Ranjbar K, Gholamali M. Effect of 8 weeks endurance training on serum vascular endothelial growth factor and endostatin in Wistar rats. Koomesh 2012; 13(4): 474-9. [In Persian].
  21. Sponder M, Dangl D, Kampf S, Fritzer-Szekeres M, Strametz-Juranek J. Exercise increases serum endostatin levels in female and male patients with diabetes and controls. Cardiovasc Diabetol 2014; 13: 6.
  22. Suhr F, Rosenwick C, Vassiliadis A, Bloch W, Brixius K. Regulation of extracellular matrix compounds involved in angiogenic processes in short- and long-track elite runners. Scand J Med Sci Sports 2010; 20(3): 441-8.
  23. Pereira F, de MR, Tibirica E, Nobrega AC. Interval and continuous exercise training produce similar increases in skeletal muscle and left ventricle microvascular density in rats. Biomed Res Int 2013; 2013: 752817.
  24. Weston KS, Wisloff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. Br J Sports Med 2014; 48(16): 1227-34.
  25. Ross LM, Porter RR, Durstine JL. High-intensity interval training (HIIT) for patients with chronic diseases. Journal of Sport and Health Science 2016; 5(2): 139-44.
  26. Francois ME, Little JP. Effectiveness and safety of high-intensity interval training in patients with type 2 diabetes. Diabetes Spectr 2015; 28(1): 39-44.
Journal of Isfahan Medical School
Volume 36, Issue 491 - Serial Number 491
July and August 2018
Pages 909-916

Files

History

  • Receive Date: 30 May 2018
  • Revise Date: 09 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics