Volume 11, Issue 4 (Autumn 2022)                   J Occup Health Epidemiol 2022, 11(4): 265-274 | Back to browse issues page

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Khajehlandi M, Bolboli L, Bolboli S. The Role of Aerobic Exercise in the Gene Expression of Metallo Proteinase-2 and Angiostatin in Diabetic Rats' Heart Tissue. J Occup Health Epidemiol 2022; 11 (4) :265-274
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1- Ph.D, Dept. of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran. , md.khajehlandi@uma.ac.ir
2- Associate Prof., Dept. of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
3- Medical Student, Faculty of Medicine, Balikesir University, Turkey.
Article history
Received: 2022/06/16
Accepted: 2022/12/1
ePublished: 2022/12/26
Subject: Epidemiology
Abstract:   (609 Views)
Background: The major effects of regular exercise on diabetes mellitus are glycemic status improvement and amelioration of cardiovascular dysfunctions. This research examines whether moderate-intensity aerobic exercise can change the gene expression of metalloproteinase-2 and angiostatin in diabetic rats' heart tissue.
Materials & Methods: In this experimental study, thirty Wistar rats were categorized into the 3 groups diabetic exercise (n = 10), sedentary diabetes (n = 10), and healthy control (n = 10). To this end, moderate-intensity aerobic exercise was performed on a treadmill for 6 weeks. Real-time PCR was used to measure metalloproteinase-2 and angiostatin gene expression. serum cortisol concentrations were measured using an ELISA kit. The one-way ANOVA and Tukey’s post-hoc test was used to check significant differences among the groups.
Results: A significant decrease in metalloproteinase-2 gene expression (P < 0/001) as well as a significant increase in angiostatin gene expression (P < 0/001) and serum cortisol concentrations (P < 0/001) were observed in the sedentary diabetes group compared to the healthy control group. Besides, a significant increase in metalloproteinase-2 gene expression (P < 0/001) as well as a significant decrease in angiostatin gene expression (P < 0/001) and serum cortisol concentrations (P < 0/001) were observed 6 weeks after the experiment in the diabetic exercise group compared to the sedentary diabetes group.
Conclusions: Aerobic exercise improved metalloproteinase-2 and angiostatin gene expression in diabetic rats' heart tissue. This finding on diabetic cardiac angiogenesis factors confirms the effect  of aerobic exercise.
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1. Sharma AK, Thanikachalam PV, Rajput SK. Albiglutide: Is a better hope against diabetes mellitus? Biomed Pharmacother. 2016 ;77:120-8. [DOI] [PMID]
2. Bachmann KN, Wang TJ. Biomarkers of cardiovascular disease: contributions to risk prediction in individuals with diabetes. Diabetologia. 2018;61(5):987-95. [DOI] [PMID] [PMCID]
3. Khajehlandi M, Bolboli L, Siahkuhian M, Rami M, Tabandeh M, Khoramipour K, et al. Endurance Training Regulates Expression of Some Angiogenesis-Related Genes in Cardiac Tissue of Experimentally Induced Diabetic Rats. Biomolecules. 2021;11(4):498. [DOI] [PMID] [PMCID]
4. Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:22. [DOI] [PMID] [PMCID]
5. Moser TL, Stack MS, Asplin I, Enghild JJ, Højrup P, Everitt L, et al. Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci U S A. 1999;96(6):2811-6. [DOI] [PMID] [PMCID]
6. Hou R, Shen M, Wang R, Liu H, Gao C, Xu J, et al. Thioredoxin1 Inactivation Mediates the Impairment of Ischemia-Induced Angiogenesis and Further Injury in Diabetic Myocardium. J Vasc Res. 2020;57(2):76-85. [DOI] [PMID]
7. Ardakanizade M. The effects of mid- and long-term endurance exercise on heart angiogenesis and oxidative stress. Iran J Basic Med Sci. 2018;21(8):800-5. [DOI] [PMID] [PMCID]
8. Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003 ;9(6):653-60. [DOI] [PMID]
9. Simunovic F, Finkenzeller G. Vascularization Strategies in Bone Tissue Engineering. Cells. 2021;10(7):1749. [DOI] [PMID] [PMCID]
10. Mihai MC, Popa MA, Suica VI, Antohe F, Jackson EK, Simionescu M, Dubey RK. Mechanism of 17β-estradiol stimulated integration of human mesenchymal stem cells in heart tissue. J Mol Cell Cardiol. 2019;133:115-24. [DOI] [PMID]
11. Mohamad HE, Askar ME, Hafez MM. Management of cardiac fibrosis in diabetic rats; the role of peroxisome proliferator activated receptor gamma (PPAR-gamma) and calcium channel blockers (CCBs). Diabetol Metab Syndr. 2011;3(1):4. [DOI] [PMID] [PMCID]
12. Webb AH, Gao BT, Goldsmith ZK, Irvine AS, Saleh N, Lee RP, et al. Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma. BMC cancer. 2017; 17(1):1-11. [DOI] [PMID] [PMCID]
13. Li Q, Sun SZ, Wang Y, Tian YJ, Liu MH. The roles of MMP-2/TIMP-2 in extracellular matrix remodelling in the hearts of STZ-induced diabetic rats. Acta Cardiol. 2007;62(5):485-91. [DOI] [PMID]
14. Sima J, Zhang SX, Shao C, Fant J, Ma JX. The effect of angiostatin on vascular leakage and VEGF expression in rat retina. FEBS Lett. 2004;564(1-2):19-23. [DOI] [PMID]
15. Claesson-Welsh L, Welsh M, Ito N, Anand-Apte B, Soker S, Zetter B, et al. Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD. Proc Natl Acad Sci U S A. 1998;95(10):5579-83 [DOI] [PMID] [PMCID]
16. Patel JV, Sosin M, Gunarathne A, Hussain I, Davis RC, Hughes EA, Lip GY. Elevated angiogenin levels in chronic heart failure. Ann Med. 2008;40(6):474-9. [DOI] [PMID]
17. Ghorbanalipour A A, Motamedi P, Rajabi H, & Karami H. The Effect of Endurance Training on Angiostatin and Enos Gene Expression of Cardiac Tissue in Type 2 Diabetic Male Wistar Rats. J Arak Uni Med Sci. 2019;21(7):112-22. []
18. 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):H428-34. [DOI] [PMID] [PMCID]
19. Thum T, Hoeber S, Froese S, Klink I, Stichtenoth DO, Galuppo P, et al. Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1. Circ Res. 2007;100(3):434-43. [DOI] [PMID]
20. Ortiz R, Kluwe B, Odei JB, Echouffo Tcheugui JB, Sims M, Kalyani RR, et al. The association of morning serum cortisol with glucose metabolism and diabetes: The Jackson Heart Study. Psychoneuroendocrinology. 2019;103:25-32. [DOI] [PMID] [PMCID]
21. Sagara R, Inoue T, Sonoda N, Yano C, Motoya M, Umakoshi H, et al. Association between cortisol and left ventricular diastolic dysfunction in patients with diabetes mellitus. J Diabetes Investig. 2022;13(2):344-50 [DOI] [PubMed] [PMCID]
22. Sgrò P, Emerenziani GP, Antinozzi C, Sacchetti M, Di Luigi L. Exercise as a drug for glucose management and prevention in type 2 diabetes mellitus. Curr Opin Pharmacol. 2021;59:95-102. [DOI] [PMID]
23. Vali Zadeh S, Motamedi P, Karami H, Rajabi H. The effects of endurance training on gene expression of VEGF and VEGFR2 of cardiac tissue in Type 2 diabetic male wistar. J Arak Uni Med Sci. 2018;21(6):107-18. [Article]
24. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001;286(10):1218-27. [DOI] [PMID]
25. Layton AT, Edwards A, Vallon V. Adaptive changes in GFR, tubular morphology, and transport in subtotal nephrectomized kidneys: modeling and analysis. Am J Physiol Renal Physiol. 2017;313(2):F199-209. [DOI] [PMID] [PMCID]
26. Crisafulli A, Pagliaro P, Roberto S, Cugusi L, Mercuro G, Lazou A, et al. Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning. Int J Mol Sci. 2020;21(8):2896. [DOI] [PMID] [PMCID]
27. Kadoglou NPE, Vrabas IS, Sailer N, Kapelouzou A, Fotiadis G, Noussios G, et al. Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes. Diabetes Metab. 2010;36(2):144-51. [DOI] [PMID]
28. Hordern MD, Coombes JS, Cooney LM, Jeffriess L, Prins JB, Marwick TH. Effects of exercise intervention on myocardial function in type 2 diabetes. Heart. 2009;95(16):1343-9. [DOI] [PMID]
29. Schrauwen-Hinderling VB, Meex RC, Hesselink MK, van de Weijer T, Leiner T, Schär M, et al. Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction. Cardiovasc Diabetol. 2011;10:47. [DOI] [PMID] [PMCID]
30. Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, et al. Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience. 2009;164(4):1665-73. [DOI] [PMID]
31. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-46. [PubMed]
32. Seguro C, Viana R, Lima G, Galvao L, Silva L, Jardim T, et al. Improvements in health parameters of a diabetic and hypertensive patient with only 40 minutes of exercise per week: a case study. Disabil Rehabil. 2020;42(21):3119-25. [DOI] [PMID]
33. Akerstrom T, Laub L, Vedel K, Brand CL, Pedersen BK, Lindqvist AK, et al. Increased skeletal muscle capillarization enhances insulin sensitivity. Am J Physiol Endocrinol Metab. 2014;307(12):E1105-16. [DOI] [PMID]
34. Bruce CR, Anderson MJ, Carey AL, Newman DG, Bonen A, Kriketos AD, Cooney GJ, Hawley JA. Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status. J Clin Endocrinol Metab. 2003;88(11):5444-51. [DOI] [PMID]
35. Khajehnasiri N, Dehkordi MB, Amini-Khoei H, Mohammadabadi MSM, Sadeghian R. Effect of exercise intensity and duration on the levels of stress hormones and hypothalamic-pituitary-gonadal axis in adult male rats: an experimental study. Hormones (Athens). 2021;20(3):483-90. [DOI] [PMID]
36. Estrada C, Cuenca L, Cano-Fernandez L, Gil-Martinez AL, Sanchez-Rodrigo C, González-Cuello AM, et al. Voluntary exercise reduces plasma cortisol levels and improves transitory memory impairment in young and aged Octodon degus. Behav Brain Res. 2019;373:112066. [DOI] [PMID]
37. Jang Y, Lee B, Kim EK, Shim WS, Yang YD, Kim SM. Involuntary swimming exercise in pregnant rats disturbs ERK1/2 signaling in embryonic neurons through increased cortisol in the amniotic fluid. Biochem Biophys Res Commun. 2018;495(1):1208-13. [DOI] [PMID]
38. Sajedi D, Shabani R, Elmieh A. Changes in leptin, serotonin, and cortisol after eight weeks of aerobic exercise with probiotic intake in a cuprizone-induced demyelination mouse model of multiple sclerosis. Cytokine. 2021;144:155590 [DOI] [PMID]
39. Rosmond R, Björntorp P. The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med. 2000;247(2):188-97. [DOI] [PMID]
40. Drust B, Waterhouse J, Atkinson G, Edwards B, Reilly T. Circadian rhythms in sports performance--an update. Chronobiol Int. 2005;22(1):21-44. [DOI] [PMID]
41. Habibian M, Khosravi M. The Effect of 8 Weeks Regular Swimming Exercise on the Cardiac Levels of Matrix Mettaloproteinase-2 and Transforming Growth Factor-Β1 in Diabetic Rats. Iran J Diabetes Metab. 2016;15(2):67-74 [Article]
42. Kwak HB, Kim JH, Joshi K, Yeh A, Martinez DA, Lawler JM. Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart. FASEB J. 2011;25(3):1106-17. [DOI] [PMID] [PMCID]
43. Farag HAM, Hosseinzadeh-Attar MJ, Muhammad BA, Esmaillzadeh A, Bilbeisi AHE. Comparative effects of vitamin D and vitamin C supplementations with and without endurance physical activity on metabolic syndrome patients: a randomized controlled trial. Diabetol Metab Syndr. 2018;10:80. [DOI] [PMID] [PMCID]
44. Taye A, Abouzied MM, Mohafez OM. Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role of oxidative stress in diabetic cardiomyopathy. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(12):1071-80. [DOI] [PMID]
45. Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev. 2004;25(4):543-67. [DOI] [PMID]
46. Seyfi Askshahr F, Khajehlandi M. The Effect of Moderate-Intensity Endurance Training on the Expression Level of Angiogenesis Factors and Cardiac Oxidative Stress in Rats. J Ardabil Uni Med Sci. 2020;20(3):361-71. [DOI]
47. Oliveira V, Akamine EH, Carvalho MH, Michelini LC, Fortes ZB, Cunha TS, et al. Influence of aerobic training on the reduced vasoconstriction to angiotensin II in rats exposed to intrauterine growth restriction: possible role of oxidative stress and AT2 receptor of angiotensin II. PLoS One. 2014;9(11):e113035. [DOI] [PMID] [PMCID]
48. Ranjbar K, Rahmani-Nia F, Shahabpour E. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction. J Physiol Biochem. 2016;72(3):393-404. [DOI] [PMID]
49. Drixler TA, Rinkes IHB, Ritchie ED, Treffers FW, van Vroonhoven TJ, Gebbink MF, et al. Angiostatin inhibits pathological but not physiological retinal angiogenesis. Invest Ophthalmol Vis Sci. 2001;42(13):3325-30. [Article]
50. Matsunaga T, Weihrauch DW, Moniz MC, Tessmer J, Warltier DC, Chilian WM. Angiostatin inhibits coronary angiogenesis during impaired production of nitric oxide. Circulation. 2002;105(18):2185-91. [DOI] [PMID]
51. Montgomery A, MacLean D. The Effect of Acute Exercise on the Interaction between Doxorubicin Administration and Nitric Oxide Metabolism in Heart and Liver Cells. FASEB J. 2021;35(S1). [DOI]
52. Inoue K, Fujie S, Hasegawa N, Horii N, Uchida M, Iemitsu K, et al. Aerobic exercise training-induced irisin secretion is associated with the reduction of arterial stiffness via nitric oxide production in adults with obesity. Appl Physiol Nutr Metab. 2020;45(7):715-22. [DOI] [PMID]

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