Document Type : Research Paper

Authors

1 PhD Student in Exercise Physiology, Shahrekord University

2 Associate Professor in Exercise Physiology, Shahrekord University

3 Assistant Professor in Exercise Physiology, Shahrekord Universitysity

4 Assistant Professor of Biology, Shahrekord University

Abstract

Aging is associated with changes in blood cholesterol and subsequent cardiovascular disease. The purpose of this study was to investigate the effect of continuous and interval endurance training on micro-RNAs associated with reverse cholesterol transport in Wistar elderly rats. 30 male Wistar rats (23-month-old) With an average weight of 441.75 gram, were randomly divided into two experiment and one control group including continuous training (n = 10), Interval training (n = 10) and the control group   (n = 10). Continuous and interval exercise included 8 weeks of training on treadmill and 5 days a week which the continuous group started training with 60% maximum speed for 16 minutes in the first week and continued with 70% maximum speed for 45 minutes from the fourth week to the end of the eighth week. The interval group started exercise at 40-80% of the maximum speed from the first week and continued at 30 to 110% of the maximum speed from the fourth week to the end of the eighth week. After completing training, expression of miR-33 and miR-144 and mRNA expression of ABCA1 were measured RT-PCR. The statistical analysis was performed using ANOVA test with significance level (P <0.05). The expression of miR-33a and miR-144 decreased in both continuous and interval groups compared to control group, but this decrease was only significance for miR-33a (P <0.001). After 8 weeks of training, mRNA expression of ABCA1 gene in the continuous and interval group increased compared to control group. However, this increase was statistically significance only for the interval group (P=0.002). There was no statistically significance difference between the effect of interval and continuous exercises on miR-33a and miR-144 expression. However, there was a significance difference in the mRNA expression of ABCA1 in both continuous and interval groups (P=0.028). Considering the results, it appears that both continuous and interval endurance trainings can decrease miR-33a expression and subsequently increase mRNA expression of the ABCA1, which this increase is higher in interval training compare continuous training.

Keywords

Main Subjects

  1. Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012;111(2):245-59.
  2. North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012;110(8):1097-108.
  3. Rotllan N, Price N, Pati P, Goedeke L, Fernandez-Hernando C. microRNAs in lipoprotein metabolism and cardiometabolic disorders. Atherosclerosis. 2016;246:352-60.
  4. Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Kimura T. Micrornas and high-density lipoprotein cholesterol metabolism. Int Heart J. 2015;56(4):365-71.
  5. Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Yokode M, et al. MicroRNA-33a/b in lipid metabolism - novel "thrifty" models. Circ J. 2015;79(2):278-84.
  6. Abente EJ, Subramanian M, Ramachandran V, Najafi-Shoushtari SH. MicroRNAs in obesity-associated disorders. Arch Biochem Biophys. 2016;589:108-19.
  7. de Aguiar Vallim T, Tarling E, Kim T, Civelek M, Baldan A, Esau C, et al. MicroRNA-144 regulates hepatic ABCA1 and plasma HDL following activation of the nuclear receptor FXR. Circulation Research. 2013;112.300648.
  8. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102-14.
  9. Rottiers V, Näär AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012;13(4):239-50.
  10. Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, et al. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE-/- mice. J Am Heart Assoc. 2012;1(6):e003376.
  11. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest. 2011;121(7):2921-31.
  12. de Aguiar Vallim TQ, Tarling EJ, Kim T, Civelek M, Baldán Á, Esau C, et al. MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor novelty and significance. Circ Res. 2013;112(12):1602-12.
  13. Ramírez CM, Rotllan N, Vlassov AV, Dávalos A, Li M, Goedeke L, et al. Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144 novelty and significance. Circ Res. 2013;112(12):1592-601.
  14. Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: Review, synthesis and recommendations. Sports Medicine. 2014;44(2):211-21.
  15. B. K. Pedersen1, B. Saltin2. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006;1:3-63.
  16. Aadahl M, von Huth Smith L, Pisinger C, Toft U, Glümer C, Borch-Johnsen K, et al. Five-year changein physical activity is associated with changes in cardiovascular disease risk factors: the Inter99 study. Prev Med. 2009;48(4):326–31.
  17. LeMura LM, von Duvillard SP, Andreacci J, Klebez JM, Chelland SA, Russo J. Lipid and lipoprotein profiles, cardiovascular fitness, body composition, and diet during and after resistance, aerobic and combination training in young women. Eur J Appl Physiol. 2000;82(5-6):451-8.
  18. O'Donovan G, Owen A, Bird SR, Kearney EM, Nevill AM, Jones DW, et al. Changes in cardiorespiratory fitness and coronary heart disease risk factors following 24 wk of moderate-or high-intensity exercise of equal energy cost.J Appl Physiol. 2005;98(5):1619-25.
  19. Ghanbari-Niaki A. Treadmill exercise training enhances ATP-binding cassette protein-A1 (ABCA1) expression in male rats’ heart and gastrocnemius muscles. Int J Endocrinol Metab. 2010;8(4):206-10.
  20. Tofighi A, Rahmani F, Qarakhanlou BJ, Babaei S. The effect of regular aerobic exercise on reverse cholesterol transport A1 and Apo lipoprotein A-I gene expression in inactive women. Iran Red Crescent Med J. 2015;17(4):e26321.
  21. Vanhees L, Geladas N, Hansen D, Kouidi E, Niebauer J, Reiner Ž, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: Recommendations from the EACPR (Part II). European Journal of Preventive Cardiology. 2012;19(5):1005-33.
  22. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328(5985):1570-3.
  23. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350-5.
  24. van der Meer SF, Jaspers RT, Jones DA, Degens H. The time course of myonuclear accretion during hypertrophy in young adult and older rat plantaris muscle. Annals of Anatomy-Anatomischer Anzeiger. 2011;193(1):56-63.
  25. Leandro CG, Levada AC, Hirabara SM, MANHAS-DE-CASTRO R, De-Castro CB, Curi R, et al. A program of moderate physical training for wistar rats based on maximal oxygen consumption. J Strength Cond Res. 2007;21(3):751-6.
  26. Rasoul Rezaei M.N, Mohammadreza Bigdeli, Fariba Khodagholi, Abbas Haghparast,. Effect of eight weeks continues and HIIT exercises on VEGF-A and VEGFR-2 levels in stratum, hippocampus and cortex of wistar rat brain. Physiology of Exercise and Physical Activity. 2016(16):1213-21. (In Persian).
  27. Kim SH, Kim GJ, Umemura T, Lee SG, Cho KJ. Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group. Mol Biol Rep. 2017;44(1):79-88.
  28. Rotllan N, Ramirez CM, Aryal B, Esau CC, Fernandez-Hernando C. Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice--brief report. Arterioscler Thromb Vasc Biol. 2013;33(8):1973-7.
  29. Ramirez CM, Rotllan N, Vlassov AV, Davalos A, Li M, Goedeke L, et al. Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circ Res. 2013;112(12):1592-601.
  30. Canfran-Duque A, Ramirez CM, Goedeke L, Lin CS, Fernandez-Hernando C. microRNAs and HDL life cycle. Cardiovasc Res. 2014;103(3):414-22.
  31. de Aguiar Vallim TQ, Tarling EJ, Kim T, Civelek M, Baldan A, Esau C, et al. MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor. Circ Res. 2013;112(12):1602-12.
  32. Kazeminasab F, Marandi M, Ghaedi K, Esfarjani F, Moshtaghian J. Effects of a 4-week aerobic exercise on lipid profile and expression of LXRα in rat liver. Cell Journal (Yakhteh). 2017;19(1):45.
  33. Marquart TJ, Allen RM, Ory DS, Baldán Á. miR-33 links SREBP-2 induction to repression of sterol transporters. Proceedings of the National Academy of Sciences. 2010;107(27):12228-32.
  34. Karunakaran D, Thrush AB, Nguyen MA, Richards L, Geoffrion M, Singaravelu R, et al. Macrophage mitochondrial energy status regulates cholesterol efflux and is enhanced by anti-miR33 in atherosclerosis. Circ Res. 2015;117(3):266-78.
  35. Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, et al. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE−/− mice. J Am Heart Assoc. 2012;1(6):e003376.
  36. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest. 2011;121(7):2921-31.