Evaluation of the effect of warfarin consumption with continuous and interval training on the expression of cardiac osteocalcin, vitamin K2 (MK-4) and serum calcium in a model of rats with myocardial infarction

Document Type : Research Paper

Authors

1 Ph.D Student in Sports Physiology, Islamic Azad University, South Tehran Branch, Tehran, Iran

2 Associate of Exercise Physiology, Islamic Azad University, South Tehran Branch, Tehran, Iran.

3 Assistant Professor of Exercise Physiology, Islamic Azad University, South Tehran Branch, Tehran, Iran

4 Department of Sport Physiology, Faculty of Physical Education, Islamic Azad University, Islamshahr Branch, Tehran, Iran.

Abstract

Abstract
Introduction:­ Exercise can minimize the risk of myocardial infarction (MI) by regulating cellular signaling in the heart and arteries. The aim of this study is to evaluate the effect of warfarin consumption with continuous and interval training on the expression of cardiac osteocalcin gene, vitamin MK-4 and serum calcium in myocardial infarction mice.
Materials and Methods:­­ In this experimental study, 42 male Sprago-Dovali rats (180-120g) were randomly divided into 7 groups: healthy control, myocardial infarction or ischemia (ISC), ISC+interval training, ISC+continuous exercise, ISC+warfarin, ISC+interval training+warfarin and ISC+continuous exercise+warfarin. Induction was induced by subcutaneous isoproterenol. The duration of training was eight weeks, five sessions per week and the dose of warfarin was 0.5 mg/kg per day. Gene values, changes in vitamin K2 and calcium were analyzed by Real time-PCR, ELISA, photometric and data analysis using independent t-test, one-way variance and two-factor variance (P<0.05).
Results: Disease induction increased the expression of osteocalcin (p=0.003), vitamin K2 (p=0.027) and calcium (p=0.001) genes compared to healthy controls. In the study of osteocalcin gene expression, ischemia+warfarin group with ischemia+EIT (p=0.014) and ischemia+ECT (p=0.007) and in the study of calcium levels of ischemia group with ischemia+EIT (p=0.014), Ischemia+ECT (p=0.001) and ischemia+warfarin+ECT (P=0.013) were significantly different. Also, the interaction between exercise and drug was not confirmed on any of the variables.
Conclusion: ­It seems that interval and continuous exercise be effective in reducing vascular degradation and calcification after MI by reducing the cardiac osteocalcin and serum calcium and minimizing the side effects of some drugs such as warfarin.

Keywords

References

  1. Wang C, Yuan Y, Zheng M, Pan A, Wang M, Zhao M, et al. Association of age of onset of hypertension with
    cardiovascular diseases and mortality. Journal of the American College of Cardiology. 2020;75(23):2921-30.
    2. Pesaro AE, Katz M, Liberman M, Pereira C, Mangueira CL, de Carvalho AE, et al. Circulating osteogenic
    proteins are associated with coronary artery calcification and increase after myocardial infarction. Plos one.
    2018;13(8):1-14.
    3. Raggi P. Coronary artery calcification predicts risk of CVD in patients with CKD. Nature Reviews Nephrology.
    2017;13(6):324-6.
    4. Gustafsson N, Ahlqvist JB, Näslund U, Wester P, Buhlin K, Gustafsson A, et al. Calcified carotid artery
    atheromas in panoramic radiographs are associated with a first myocardial infarction: a case-control study. Oral
    surgery, oral medicine, oral pathology and oral radiology. 2018;125(2):199-204.
    5. Zoch ML, Clemens TL, Riddle RC. New insights into the biology of osteocalcin. Bone. 2016;82:42-9.
  2. 6. Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, et al. Oxidative stress induces vascular
    calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. Journal of
    Biological Chemistry. 2008;283(22):15319-27.
    7. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM. Osteo/chondrocytic transcription
    factors and their target genes exhibit distinct patterns of expression in human arterial calcification.
    Arteriosclerosis, thrombosis, and vascular biology. 2003;23(3):489-94.
    8. Guessous I, Bochud M, Bonny O, Burnier M. Calcium, vitamin D and cardiovascular disease. Kidney and
    Blood Pressure Research. 2011;34(6):404-17.
    9. Tantisattamo E, Han KH, O’Neill WC. Increased vascular calcification in patients receiving warfarin.
    Arteriosclerosis, thrombosis, and vascular biology. 2015;35(1):237-42.
    10. Hartley L, Clar C, Ghannam O, Flowers N, Stranges S, Rees K. Vitamin K for the primary prevention of
    cardiovascular disease. Cochrane Database of Systematic Reviews. 2015;(9): CD011148:1-23.
    11. Singulani MP, Stringhetta-Garcia CT, Santos LF, Morais SRL, Louzada MJQ, Oliveira SHP, et al. Effects of
    strength training on osteogenic differentiation and bone strength in aging female Wistar rats. Scientific reports.
    2017;7(42878):1-11.
    12. Rostamizadeh M, Elmieh A, Rahmani Nia F. Effects of Aerobic and Resistance Exercises on Anthropometric
    Indices and Osteocalcin, Leptin, Adiponectin Levels in Overweight Men. Journal of Arak University of Medical
    Sciences. 2019;22(1):85-95.
    13. Keikhosravi F, Daryanoosh F, Koushkie Jahromi M, Nemati J. High-Intensity Interval Training Effects with
    Genistein on Serum Osteocalcin and Bone Alkaline Phosphatase in Female Elderly Rats. Journal of Nutrition,
    Fasting and Health. 2021;9(2):125-30.
    14. Abdi H, Bolboli L, Afroundeh R, Siahkohian M, Khajehlandi M. The Effect of One Course of Intense Interval
    Training on Serum Levels of Vitamin D, Heart Rate Variability and Lung Function in Male Smokers: A QuasiExperimental Study. Journal of Rafsanjan University of Medical Sciences. 2021;20(3):277-96.
    15. Doroudgar, S. and C.C. Glembotski, The cardiokine story unfolds: ischemic stress-induced protein secretion
    in the heart. Trends in molecular medicine, 2011;17(4):207-214.
    16. Chiba, A., et al., Cardiomyokines from the heart. Cellular and Molecular Life Sciences, 2018: 75, 1349–1362.
    17. Xi, Y., D.-W. Gong, and Z. Tian, FSTL1 as a potential mediator of exercise-induced cardioprotection in postmyocardial infarction rats. Scientific reports, 2016;6: 32424.
    18. Rebholz, C.M., et al., Physical activity reduces salt sensitivity of blood pressure: the Genetic Epidemiology
    Network of Salt Sensitivity Study. American journal of epidemiology, 2012;176 (S 7): S106-S113.
    19. Shendre, A., et al., Influence of regular physical activity on warfarin dose and risk of hemorrhagic
    complications. Pharmacotherapy, 2014;34(6): 545-554
    20. E´tienne Rouleau-Mailloux, Payman Shahabi, Ste´phanie Dumas. Impact of regular physical activity on
    weekly warfarin dose Requirement. DOI 10.1007/s11239-015-1248-9. J Thromb Thrombolysis (2016) 41:328–
    335.
    21. Hosseini M, Bambaeichi E, Sarir H, Kargarfard M. Effect of training with or without Ziziphus jujuba extract
    on cardiokines in heart tissue of myocardial infarcted rats. Int J Prev Med 2019; 10(103): 1-5.
    22. Eizadi M, Soory R, Ravasi A, Baesy K, Choobineh S. Relationship between TCF7L2 Relative Expression in
    Pancreas Tissue with Changes in Insulin by High Intensity Interval Training (HIIT) in Type 2 Diabetes Rats.
    SSU_Journals. 2017;24(12):981-93. [Farsi]
    23. Hadi H, Gaeini A, Mo'tamedi P, Rajabi H. The effect of aerobic training on cardiac expression of mir-126 in
    diabetic rats. J Police med. 2016; 5(1): 69-78. [Farsi]
    24. Zhang X, Zhang X, Wang X, Zhao M. Influence of andrographolide on the pharmacokinetics of warfarin in
    rats. Pharmaceutical biology. 2018;56(1):351-6.
    25. Mohebbi H, Rahmani-Nia F, yar Arabmomeni A, Riasi A, Marandi M. The effects of interval training and age
    on blood lactate (La) levels and lactate dehydrogenase (LDH) activity in male Wistar rats. Par J Med Sci 2015;
    12(4): 37-45.
    26. Santoso DIS, Yunita S, Paramita N, Andraini T, Kartinah NT, El Bayani GF, et al. Effect of Hibiscus sabdariffa
    Linn on IL-6 and TNF-α levels in overtrained rat heart. Int J Appl Pharm 2019; 11 (6): 42-5.
    27. Johansson S, Rosengren A, Young K, Jennings E. Mortality and morbidity trends after the first year in
    survivors of acute myocardial infarction: a systematic review. BMC Cardiovascular Disorders. 2017;17(53):1-8.
    28. Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nature Reviews Cardiology.
    2010;7(9):528-36.
    29. Ghasemalipour H, Eizadi M. The effect of aerobic training on some bone formation markers (osteocalcin,
    alkaline phosphatase) in asthma treated with inhaled corticosteroids. Zahedan Journal of Research in Medical
    Sciences. 2018;20(1):1-9.
    30. Yardley JE. Fasting may alter blood glucose responses to high-intensity interval exercise in adults with type
    1 diabetes: a randomized, acute crossover study. Canadian Journal of Diabetes. 2020;44(8):727-33.
  3. 31. Jiang Y, Tan S, Wang Z, Guo Z, Li Q, Wang J. Aerobic exercise training at maximal fat oxidation intensity
    improves body composition, glycemic control, and physical capacity in older people with type 2 diabetes. Journal
    of exercise science & fitness. 2020;18(1):7-13.
    32. Bowman PR, Smith GL, Gould GW. Run for your life: can exercise be used to effectively target GLUT4 in
    diabetic cardiac disease? PeerJ. 2021;9:e11485:1-35.
    33. Dun Y, Thomas RJ, Smith JR, Medina-Inojosa JR, Squires RW, Bonikowske AR, et al. High-intensity interval
    training improves metabolic syndrome and body composition in outpatient cardiac rehabilitation patients with
    myocardial infarction. Cardiovascular diabetology. 2019;18(104):1-11.
    34. Morishima Y, Kamisato C, Honda Y, Furugohri T, Shibano T. The effects of warfarin and edoxaban, an oral
    direct factor Xa inhibitor, on gammacarboxylated (Gla-osteocalcin) and undercarboxylated osteocalcin (ucosteocalcin) in rats. Thrombosis research. 2013;131(1):59-63.
    35. Radulescu D, Stroescu A, Pricop C, Geavlete B, Negrei C, Bratu O, et al. Vitamin K influence on
    cardiovascular mortality in chronic hemodialysed patients. Rev Chim (Bucharest). 2017;68(1):52-4.
    36. Sabrina-Wong-Peixin Haroon B-C, Tai L-HL, Lynette Teo AD, Leon Schurgers B-WT, Priyanka Khatri CCO, Sanmay Low X-EY, et al. Treatment to reduce vascular calcification in hemodialysis patients using vitamin
    K (Trevasc-HDK): a study protocol for a randomized controlled trial. Medicine. 2020;99(36): 1-8.
    37. Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, Kaczmarska M, Stefańczyk L, Vermeer C, et al. Effect of
    vitamin K. Polskie Archiwum Medycyny Wewnętrznej. 2015;125(9):631-40.
    38. Girolami A, Ferrari S, Cosi E, Santarossa C, Randi ML. Vitamin K-dependent coagulation factors that may
    be responsible for both bleeding and thrombosis (FII, FVII, and FIX). Clinical and Applied
    Thrombosis/Hemostasis. 2018;24(9S):42S-7S.
    39. McFarlin BK, Henning AL, Venable AS. Oral Consumption of Vitamin K2 for 8 Weeks Associated With
    Increased Maximal Cardiac Output During Exercise. Alternative Therapies in Health & Medicine. 2017;23(4):26-
    32.
    40. Reid I, Gamble G, Bolland M. Circulating calcium concentrations, vascular disease and mortality: a systematic
    review. Journal of internal medicine. 2016;279(6):524-40.
    41. Barry EL, Mott LA, Melamed ML, Rees JR, Ivanova A, Sandler RS, et al. Calcium supplementation increases
    blood creatinine concentration in a randomized controlled trial. PloS one. 2014;9(10):e108094.1-9.
    42. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and
    risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and metaanalysis. Bmj. 2011;342:1-9.
    43. Sultana RN, Sabag A, Keating SE, Johnson NA. The effect of low-volume high-intensity interval training on
    body composition and cardiorespiratory fitness: a systematic review and meta-analysis. Sports Medicine.
    2019;49(11):1687-721.
    44. Zhang S-S, Zhou S, Crowley-McHattan ZJ, Wang R-Y, Li J-P. A Review of the Role of Endo/Sarcoplasmic
    Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function. International Journal of
    Environmental Research and Public Health. 2021;18(8):3874:1-12.
    45. Yengo CM, Zimmerman SD, McCormick RJ, Thomas DP. Exercise training post-MI favorably modifies heart
    extracellular matrix in the rat. Medicine and science in sports and exercise. 2012;44(6):1005-12.
    46. Elango K, Javaid A, Khetarpal BK, Ramalingam S, Kolandaivel KP, Gunasekaran K, et al. The Effects of
    Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review. Cells. 2021;10(4):773:
    1-14.
medical journal of mashhad university of medical sciences
Volume 65, Issue 2
May and June 2022
Pages 712-729

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