The effect of 8 weeks of aerobic training and vitamins E & C supplementation on the plasma levels of MMP-1 and MMP-3 and TIMP-4 in patients with Coronary artery disease
Subject Areas : Journal of Physical Activity and Hormones
Elham Karami
1
,
Ramin Shabani
2
,
Farhad Rahmani-Nia
3
,
Alireza Elmieh
4
,
Mahdi Rezagholizadeh
5
1 -
2 -
3 -
4 -
5 -
Keywords: Cardiac artery diseases, Aerobic training, Rehabilitation, Vitamins E & C supplementation,
Abstract :
Introduction: The family of matrix metalloproteinases (MMPs) and its inhibitors play an important role in cardiovascular diseases and vascular wall regeneration. The effect of sports training along with vitamin supplements on heart diseases due to the change of MMPs is not clear. Therefore, the aim of the present study is investigating the effect of eight weeks of aerobic training with vitamin E & C supplementation on the plasma levels of MMP-1 and MMP-3 and TIMP-4 in patients with coronary artery disease (CAD).
Material & Methods: 60 patients with CAD (53.84±5.49 years old mean ± SD) participated in this study., All the subjects were randomly divided into 4 equal groups (n=15): (1) control (C), (2) aerobic training (A), (3) supplement (S) and (4) aerobic training + supplement (AS) according to their aerobic capacity: and Groups 3 and 4 received 1000 mg of D-alpha tocopherol and 1000 mg acid ascorbic tablets daily. . The training program was also carried out for eight weeks (three sessions per week) with an intensity of 40 to 80% of the reserve heart rate for 45 minutes. 48 hours after the last session of training, blood samples were taken to analyze MMPs levels by using ELISA. The data were analyzed using analysis of covariance and paired t-test at a significance level of P<0.05.
Results: The plasma levels of MMP-1 (P=0.001) and MMP-3 (P=0.000) in the AS were significantly lower than the A group. TIMP-4 concentration in the AS group were significantly higher than in the A group (P=0.000). In addition, plasma MMP-1 and MMP-3 levels in patients with CAD in the AS group were significantly lower than in the S group (P=0.000) and C group (P=0.000). Also, plasma MMP-1 and MMP-3 levels in patients with CAD in the T group were significantly lower than in the C group (P=0.000). However, plasma MMP-1 (P=0.068), MMP-3 (P=0.069), and TIMP-4 (P=1.000) levels in patients with CAD in the T group were not significantly different from those in the S group. Also, plasma MMP-1 (P=0.055), MMP-3 (P=0.392), and TIMP-4 (P=0.405) levels in patients with CAD in the S group were not significantly different from those in the C group. In addition, plasma TIMP-4 levels in patients with CAD in the AS group were significantly higher than in the supplement (P=0.000) and control (P=0.000) groups. Also, plasma TIMP-4 levels in patients with CAD in the A group were significantly higher than in the C group (P=0.021).
Conclusion: combined aerobic training and taking vitamin E and C supplements can affect the plasma levels of the mentioned indicators to a greater extent and cause them to improve, which displays the higher efficiency of training at the same time as the supplement.
1. Sharma K, Gulati M. Coronary artery disease in women: a 2013 update. Global heart. 2013;8(2):105-12. https://doi.org/10.1016/j.gheart.2013.02.001.
2. Sanjadi M, Rezvanie Sichanie Z, Totonchi H, Karami J, Rezaei R, Aslani S. Atherosclerosis and autoimmunity: a growing relationship. International journal of rheumatic diseases. 2018;21(5):908-21. https://doi.org/10.1111/1756-185X.13309.
3. Mayer B, Erdmann J, Schunkert H. Genetics and heritability of coronary artery disease and myocardial infarction. Clinical Research in Cardiology. 2007;96(1):1-7. https://doi.org/10.1007/s00392-006-0447-y.
4. Mack M, Gopal A. Epidemiology, traditional and novel risk factors in coronary artery disease. Heart failure clinics. 2016;12(1):1-10. DOI: 10.1016/j.hfc.2015.08.002.
5. Giannakoulas G, Dimopoulos K, Engel R, Goktekin O, Kucukdurmaz Z, Vatankulu MA, et al. Burden of coronary artery disease in adults with congenital heart disease and its relation to congenital and traditional heart risk factors. The American journal of cardiology. 2009;103(10):1445-50. https://doi.org/10.1016/j.amjcard.2009.01.353.
6. Evans A, Van Baal GCM, McCarron P, DeLange M, Soerensen TI, De Geus EJ, et al. The genetics of coronary heart disease: the contribution of twin studies. Twin Research and Human Genetics. 2003;6(5):432-41. https://doi.org/10.1375/twin.6.5.432.
7. Sayols-Baixeras S, Lluís-Ganella C, Lucas G, Elosua R. Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants. The application of clinical genetics. 2014:15-32. https://doi.org/10.2147/TACG.S35301.
8. Onrat ST, Akci Ö, Söylemez Z, Onrat E, Avşar A. Prevalence of myocardial infarction polymorphisms in Afyonkarahisar, Western Turkey. Molecular biology reports. 2012;39:9257-64. https://doi.org/10.1007/s11033-012-1799-1.
9. Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet. 2004;5(1):189-218. https://doi.org/10.1146/annurev.genom.5.061903.175930.
10. Mogharrabi M, Rahimi HR, Hasanzadeh S, Dastani M, Kazemi-Oskuee R, Akhlaghi S, et al. The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial. ARYA atherosclerosis. 2020;16(3):136. https://doi.org/10.22122/arya.v16i3.1938.
11. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annual review of cell and developmental biology. 2001;17(1):463-516. https://doi.org/10.1146/annurev.cellbio.17.1.463.
12. Wenwang L. Susceptibility of MMP3 gene polymorphism to coronary artery disease: A meta-analysis. Journal of Medical Biochemistry. 2023;42(4):685. https://doi.org/10.5937/jomb0-43315.
13. Mittal B, Mishra A, Srivastava A, Kumar S, Garg N. Matrix metalloproteinases in coronary artery disease. Advances in clinical chemistry. 2014;64:1-72. https://doi.org/10.1016/B978-0-12-800263-6.00001-X.
14. Fletcher EK, Wang Y, Flynn LK, Turner SE, Rade JJ, Kimmelstiel CD, et al. Deficiency of MMP1a (matrix metalloprotease 1a) collagenase suppresses development of atherosclerosis in mice: translational implications for human coronary artery disease. Arteriosclerosis, thrombosis, and vascular biology. 2021;41(5):e265-e79. https://doi.org/10.1161/ATVBAHA.120.315837.
15. Pleskovic A, Letonja MS, Vujkovac AC, Starcevic JN, Caprnda M, Curilla E, et al. Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus. Vasa. 2017;46(5):363-9. https://doi.org/10.1024/0301-1526/a000637.
16. Fragão-Marques M, Miranda I, Martins D, Barroso I, Mendes C, Pereira-Neves A, et al. Atrial matrix remodeling in atrial fibrillation patients with aortic stenosis. BMC Cardiovascular Disorders. 2020;20:1-13. https://doi.org/10.1186/s12872-020-01754-0.
17. Kuliczkowski W, Radomski M, Gąsior M, Urbaniak J, Kaczmarski J, Mysiak A, et al. MMP‐2, MMP‐9, and TIMP‐4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study. BioMed research international. 2017;2017(1):9352015. https://doi.org/10.1155/2017/9352015.
18. Dalal HM, Doherty P, Taylor RS. Cardiac rehabilitation. Bmj. 2015;351. https://doi.org/10.1136/bmj.h5000.
19. Clarke MW, Burnett JR, Croft KD. Vitamin E in human health and disease. Critical reviews in clinical laboratory sciences. 2008;45(5):417-50. https://doi.org/10.1080/10408360802118625.
20. Navab M, Ananthramaiah G, Reddy ST, Van Lenten BJ, Ansell BJ, Fonarow GC, et al. Thematic review series: the pathogenesis of atherosclerosis the oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. Journal of lipid research. 2004;45(6):993-1007. https://doi.org/10.1194/jlr.R400001-JLR200.
21. Lee C-H, Chan RS, Wan HY, Woo Y-C, Cheung CY, Fong CH, et al. Dietary intake of anti-oxidant vitamins A, C, and E is inversely associated with adverse cardiovascular outcomes in chinese—A 22-years population-based prospective study. Nutrients. 2018;10(11):1664. https://doi.org/10.3390/nu10111664.
22. de Oliveira Otto MC, Alonso A, Lee D-H, Delclos GL, Bertoni AG, Jiang R, et al. Dietary Intakes of Zinc and Heme Iron from Red Meat, but Not from Other Sources, Are Associated with Greater Risk of Metabolic Syndrome and Cardiovascular Disease3. The Journal of nutrition. 2012;142(3):526-33. https://doi.org/10.3945/jn.111.149781.
23. Wang T, Xu L. Circulating vitamin E levels and risk of coronary artery disease and myocardial infarction: a Mendelian randomization study. Nutrients. 2019;11(9):2153. https://doi.org/10.3390/nu11092153.
24. Goyal A, Terry MB, Siegel AB. Serum antioxidant nutrients, vitamin A, and mortality in US adults. Cancer Epidemiology, Biomarkers & Prevention. 2013;22(12):2202-11. https://doi.org/10.1158/1055-9965.EPI-13-0381.
25. Karppi J, Laukkanen JA, Mäkikallio TH, Kurl S. Low serum lycopene and β-carotene increase risk of acute myocardial infarction in men. The European Journal of Public Health. 2012;22(6):835-40. https://doi.org/10.1093/eurpub/ckr174.
26. Nagao M, Moriyama Y, Yamagishi K, Iso H, Tamakoshi A. Relation of serum α-and γ-tocopherol levels to cardiovascular disease-related mortality among Japanese men and women. Journal of epidemiology. 2012;22(5):402-10. https://doi.org/10.2188/jea.JE20120002.
27. Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, et al. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The American journal of clinical nutrition. 2006;84(5):1200-7. https://doi.org/10.1093/ajcn/84.5.1200.
28. Mezzetti A, Zuliani G, Romano F, Costantini F, Pierdomenico SD, Cuccurullo F, et al. Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people. Journal of the American Geriatrics Society. 2001;49(5):533-7. https://doi.org/10.1046/j.1532-5415.2001.49110.x.
29. Hantke B, Lahmann C, Venzke K, Fischer T, Kocourek A, Jack Windsor L, et al. Influence of flavonoids and vitamins on the MMP-and TIMP-expression of human dermal fibroblasts after UVA irradiation. Photochemical & Photobiological Sciences. 2002;1:826-33. https://doi.org/10.1039/b207731k.
30. Khatami PG, Soleimani A, Sharifi N, Aghadavod E, Asemi Z. The effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial. Journal of clinical lipidology. 2016;10(4):922-9. https://doi.org/10.1016/j.jacl.2016.02.021.
31. Heidarnia E, Taghian F, Dehkordi KJ, Moghadasi M. The effect of combined training and consumption of e and C antioxidant supplements on mitochondrial function and biogenesis in the heart tissue of diabetic rats. 30 January 2022, Vol. 21, No. 5, fa323-fa332, en333 ref. 42 ref. https://ijdld.tums.ac.ir/article-1-6093-en.html.
32. Fitzhugh EC, Thompson DL. Leisure-time walking and compliance with ACSM/AHA aerobic-related physical activity recommendations: 1999–2004 NHANES. Journal of Physical Activity and Health. 2009;6(4):393-402. https://doi.org/10.1123/jpah.6.4.393.
33. Mueller K, Hingst J. The athlete's guide to sports supplements: Human Kinetics; 2013.
34. Jourkesh M, Ostojic SM, Azarbayjani M. The effects of vitamin E and vitamin C supplementation on bioenergetics index. Research in sports medicine. 2007;15(4):249-56. https://doi.org/10.1080/15438620701693249.
35. Pourghane P, Hosseini M-A, Mohammadi F, Ahmadi F, Tabari R. Patient's perception of cardiac rehabilitation after coronary artery bypass graft (CABG): A qualitative study. Journal of Mazandaran University of Medical Sciences. 2013;23(106):61-76. http://jmums.mazums.ac.ir/article-1-2196-en.html.
36. Moholdt TT, Amundsen BH, Rustad LA, Wahba A, Løvø KT, Gullikstad LR, et al. Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: a randomized study of cardiovascular effects and quality of life. American heart journal. 2009;158(6):1031-7. https://doi.org/10.1016/j.ahj.2009.10.003.
37. Olfert IM, Howlett RA, Wagner PD, Breen EC. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2010;299(4):R1059-R67. https://doi.org/10.1152/ajpregu.00347.2010.
38. Higgins MR, Izadi A, Kaviani M. Antioxidants and exercise performance: with a focus on vitamin E and C supplementation. International journal of environmental research and public health. 2020;17(22):8452. https://doi.org/10.3390/ijerph17228452.
39. Holvoet P. Obesity, the metabolic syndrome, and oxidized LDL. The American journal of clinical nutrition. 2006;83(6):1438-9. https://doi.org/10.1093/ajcn/83.6.1438.
40. Vo HVT, Nguyen YT, Kim N, Lee HJ. Vitamin A, D, E, and K as matrix metalloproteinase-2/9 regulators that affect expression and enzymatic activity. International journal of molecular sciences. 2023;24(23):17038. https://doi.org/10.3390/ijms242317038.
41. Jaoude J, Koh Y. Matrix metalloproteinases in exercise and obesity. Vascular health and risk management. 2016:287-95. https://doi.org/10.2147/VHRM.S103877.
42. Mirtaheri E, Khabbazi A, Nazemiyeh H, Ebrahimi A-A, Hajalilou M, Shakibay Novin Z, et al. Stachys schtschegleevii tea, matrix metalloproteinase, and disease severity in female rheumatoid arthritis patients: a randomized controlled clinical trial. Clinical Rheumatology. 2022;41(4):1033-44. https://en.irct.ir/trial/11602.
43. Hu Y-C, Huang T-C, Huang L-W, Cheng H-L, Hsieh B-S, Chang K-L. S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation. Nutrients. 2024;16(14):2364. https://doi.org/10.3390/nu16142364.
44. Alblooshi AG. THE EFFECT OF LICOGLIFLOZIN (SGLT1/2 INHIBITOR) ON DIABETES AND CARDIAC COMPLICATIONS. 2022.
45. Lim Y-J, Min H-Y, Jang W-G. Zingerone attenuates pi-induced vascular calcification via AMPK-mediated TIMP4 expression. Journal of Lipid and Atherosclerosis. 2021;10(1):62. https://doi.org/10.12997/jla.2021.10.1.62.
46. Hughes WM, Rodriguez WE, Rosenberger D, Chen J, Sen U, Tyagi N, et al. Role of copper and homocysteine in pressure overload heart failure. Cardiovascular toxicology. 2008;8:137-44. https://doi.org/10.1007/s12012-008-9021-3.
47. Sozen E, Demirel T, Ozer NK. Vitamin E: Regulatory role in the cardiovascular system. Iubmb Life. 2019;71(4):507-15. https://doi.org/10.1002/iub.2020.