Influence of concurrent and functional training on miR-1/miR-126 gene expression and cardiovascular function in postmenopausal women

Document Type : Original Article

Authors

1 Professor at Exercise Physiology, Exercise Physiology Department, Sport Sciences Faculty, Shahid Rajaee Teacher Training University, Tehran, Iran.

2 Associate Professor at Exercise Physiology, Exercise Physiology Department, Sport Sciences Faculty, Shahid Rajaee Teacher Training University, Tehran, Iran.

3 Assistant Professor at Exercise Physiology, Exercise Physiology Department, Sport Sciences Faculty, Shahid Rajaee Teacher Training University, Tehran, Iran.

4 Ph.D. candidate at Exercise Physiology, Exercise Physiology Department, Sport Sciences Faculty, Shahid Rajaee Teacher Training University, Tehran, Iran

Abstract

It is becoming more important to understand the physiological processes that contribute to the emergence of risk factors associated with menopause, and to discover strategies for preventing and reversing them. The current research aimed to determine the impact of functional and concurrent training on miR-126/miR-1 gene expression, and cardiovascular function in middle-aged postmenopausal women. In this study, 24 women between the ages of 50 and 60 years old with a sedentary life style participated. The subjects were randomly divided into the control group, concurrent training group, and functional training group. The Control received no intervention, and the experimental groups performed selected training protocols for 12 weeks. Doppler ultrasound graphs were utilized after the interventions to evaluate the cardiovascular function. Also, 48 hours after experiment, the blood collection was taken to assess miR-126/miR-1 gene expression. To compare the variables, one-way ANOVA test followed by Tukey's post hoc test was used. The significance level was set at p < 0.05. The results showed that the training programs led to significant enhancements in FLOW-mediated dilation, and PSV (peak systolic velocity). Moreover, there was a significant decrease in the vascular stiffness in the participants after undergoing the training. Additionally, miR-1 and miR-126 gene expression were found to be increased in response to both training interventions. These findings suggest that concurrent and functional training may be an effective approach for reducing the risk of age-related diseases in menopausal women through promoting cardiovascular functions and miR-126/miR-1 gene expression elevation.

What is already known on this subject?

Physical activity is essential for maintaining a healthy cardiovascular system, which consists of the heart, blood vessels, and blood. By engaging in regular exercise, people can improve the function and structure of their cardiovascular system, as well as prevent or treat various diseases that affect it. Some of the positive effects of physical activity include reducing oxidative stress and inflammation, enhancing insulin sensitivity and metabolism, promoting stem cell repair, strengthening cellular energy production, increasing vascular dilation and blood flow, and enlarging and strengthening the heart muscle. Therefore, physical activity can help people achieve optimal cardiovascular health and well-being.

 

What this study adds?

Engaging in functional and concurrent exercise training can have beneficial outcomes, such as enhancing the levels of mir1 and miR-126, two types of microRNAs that are involved in regulating angiogenesis and inflammation, increasing PSV and FMD, two measures of vascular function that reflect the ability of blood vessels to dilate and respond to changes in blood flow, and lowering Stifnex index, a measure of arterial stiffness that indicates the risk of cardiovascular disease. Therefore, exercise can be regarded as a safe and effective way to improve the overall health and well-being of women who are going through menopause.

Keywords

Main Subjects


Acknowledgements

We gratefully thank the subjects for their participation in this study.

Funding

None.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval This study was approved by the Ethical Standards of the Institutional and/or National Research Committee (IR.SSRI.REC.1401.177).  Informed consent was obtained from all participants.

Informed consent Informed consent was taken from all subjects. 

Author contributions

Conceptualization: M.K, F.S, H.S, L.G.; Methodology: M.K, F.S, H.S, L.G.; Software: M.K, F.S, H.S, L.G.; Validation: M.K, F.S, H.S, L.G.; Formal analysis; M.K, F.S, H.S, L.G.; Investigation: M.K, F.S, H.S, L.G.; Resources: M.K, F.S, H.S, L.G.; Data curation: M.K, F.S, H.S, L.G.; Writing - original draft: M.K, F.S, H.S, L.G.; Writing – review & editing: M.K, F.S, H.S, L.G.; Visualization: M.K, F.S, H.S, L.G.; Supervision: L.G.; Project administration: L.G..; Funding acquisition: M.K.

Ai, Jing, Rong Zhang, Yue Li, Jielin Pu, Yanjie Lu, Jundong Jiao, Kang Li, Bo Yu, Zhuqin Li, and Rongrong Wang. 2010. 'Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction', Biochemical and Biophysical Research Communications, 391: 73-77. DOI: https://doi.org/10.1016/j.bbrc.2009.11.005
Aliyeva, Amina M, Natalya V Teplova, Aleksey V Butenko, Evgeniy E Averin, Madina F Akhmedova, Yulia A Shikhova, Ramiz K Valiev, Muhammetsakhet N Sariyev, Irina A Kotikova, and Igor G Nikitin. 2023. 'MicroRNA-1 and microRNA-133: Small molecules of great importance in the aspect of cardiovascular diseases', Therapy, 9: 72-79. DOI: https://doi.org/10.1080/13813455.2021.1880995
Batty, Matthew, Martin R Bennett, and Emma Yu. 2022. 'The role of oxidative stress in atherosclerosis', Cells, 11: 3843. DOI: https://doi.org/10.3390/cells11153843
Bavkar, Laxman N, Rahul S Patil, Sheetalnath B Rooge, Megha L Nalawade, and Akalpita U Arvindekar. 2019. 'Acceleration of protein glycation by oxidative stress and comparative role of antioxidant and protein glycation inhibitor', Molecular and Cellular Biochemistry, 459: 61-71. DOI: https://doi.org/10.1007/s11010-019-03581-0
Bays, Harold E, Pam R Taub, Elizabeth Epstein, Erin D Michos, Richard A Ferraro, Alison L Bailey, Heval M Kelli, Keith C Ferdinand, Melvin R Echols, and Howard Weintraub. 2021. 'Ten things to know about ten cardiovascular disease risk factors', American Journal of Preventive Cardiology, 5: 100149. DOI: https://doi.org/10.1016/j.ajpc.2020.100149
Biglia, Nicoletta, Luca Mariani, Luca Sgro, Paola Mininanni, Giulia Moggio, and Piero Sismondi. 2007. 'Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment', Endocrine-related cancer, 14: 549-67. DOI: https://doi.org/10.1677/ERC-07-0074
Birukov, Anna, Rafael Cuadrat, Elli Polemiti, Fabian Eichelmann, and Matthias B Schulze. 2021. 'Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals: a cross-sectional study', Cardiovascular Diabetology, 20: 1-11. DOI: https://doi.org/10.1186/s12933-021-01224-8
Brisebois, Matthew. 2019. Acute Effects of Concurrent Exercise on Biomarkers of Angiogenesis and Cardioprotection in Sedentary Adults (Texas Woman's University). No DOI available 
Carresi, Cristina, Rocco Mollace, Roberta Macrì, Miriam Scicchitano, Francesca Bosco, Federica Scarano, Anna Rita Coppoletta, Lorenza Guarnieri, Stefano Ruga, and Maria Caterina Zito. 2021. 'Oxidative stress triggers defective autophagy in endothelial cells: role in atherothrombosis development', Antioxidants, 10: 387. DOI: https://doi.org/10.3390/antiox10030387
Dilsiz, Nihat. 2020. 'Role of exosomes and exosomal microRNAs in cancer', Future science OA, 6: FSO465. DOI: https://doi.org/10.2144/fsoa-2019-0128
Duarte, Filipe V, Carlos M Palmeira, and Anabela P Rolo. 2014. 'The role of microRNAs in mitochondria: small players acting wide', Genes, 5: 865-86. DOI: https://doi.org/10.3390/genes5040865
Flensted-Jensen, Mathias, Martin Gram, Flemming Dela, Jørn Wulff Helge, and Steen Larsen. 2021. 'Six weeks of high intensity cycle training reduces H2O2 emission and increases antioxidant protein levels in obese adults with risk factors for type 2 diabetes', Free Radical Biology and Medicine, 173: 1-6. OI: https://doi.org/10.1016/j.freeradbiomed.2021.06.001
Gliemann, Lasse, Camilla Vestergaard Hansen, Nicolai Rytter, and Ylva Hellsten. 2019. 'Regulation of skeletal muscle blood flow during exercise', Current Opinion in Physiology, 10: 146-55. DOI: https://doi.org/10.1016/j.cophys.2019.07.003
Gupta, Shashi K, Claudia Bang, and Thomas Thum. 2010. 'Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease', Circulation: Cardiovascular Genetics, 3: 484-88. DOI: https://doi.org/10.1161/CIRCGENETICS.110.957415
Hartono, Felicia A, Patrick W Martin-Arrowsmith, Wouter M Peeters, and Tyler A Churchward-Venne. 2022. 'The effects of dietary protein supplementation on acute changes in muscle protein synthesis and longer-term changes in muscle mass, strength, and aerobic capacity in response to concurrent resistance and endurance exercise in healthy adults: a systematic review', Sports Medicine, 52: 1295-328. DOI: https://doi.org/10.1007/s40279-022-01560-4
Hashemzadeh, Mehrnoosh, Ryan Romo, Joseph M Arreguin, and Mohammed Reza Movahed. 2020. 'The effects of estrogen and hormone replacement therapy on cardiovascular systems', Future cardiology, 17: 347-53. DOI: https://doi.org/10.2217/fca-2020-0013
Hibbs, Angela E, Kevin G Thompson, Duncan French, Allan Wrigley, and Iain Spears. 2008. 'Optimizing performance by improving core stability and core strength', Sports Medicine, 38: 995-1008. DOI: https://doi.org/10.2165/00007256-200838120-00004
Ioakeimidis, Nikolaos, Charalambos Vlachopoulos, Konstantinos Rokkas, Zisis Kratiras, Athanasios Angelis, Alexis Samentzas, Charalambos Fassoulakis, and Dimitris Tousoulis. 2016. 'Dynamic penile peak systolic velocity predicts major adverse cardiovascular events in hypertensive patients with erectile dysfunction', Journal of Hypertension, 34: 860-68. DOI: https://doi.org/10.1097/HJH.0000000000000858
Jian, Bin, Zhen Li, Tao Zhang, Li Guo Tan, and Can Can Qiang. 2021. 'The Expression Changes and Clinical Significance of Serum miRNA-1 in Patients with Heart Failure', Indian Journal of Pharmaceutical sciences: 111-15. DOI: https://doi.org/10.36468/pharmaceutical-sciences.803
Jiménez‐Aranda, Aroa, Gumersindo Fernández‐Vázquez, Daniel Campos, Mohamed Tassi, Lourdes Velasco‐Perez, Dun‐Xian Tan, Russel J Reiter, and Ahmad Agil. 2013. 'Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats', Journal of pineal research, 55: 416-23. DOI: https://doi.org/10.1111/jpi.12089
Kalyani, Rita Rastogi, Mark Corriere, and Luigi Ferrucci. 2014. 'Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases', The lancet Diabetes & endocrinology, 2: 819-29. DOI: https://doi.org/10.1016/S2213-8587(14)70034-8
Ko, Seong-Hee, and Hyun-Sook Kim. 2020. 'Menopause-associated lipid metabolic disorders and foods beneficial for postmenopausal women', Nutrients, 12: 202. DOI: https://doi.org/10.3390/nu12010202
Kura, Branislav, Mihir Parikh, Jan Slezak, and Grant N Pierce. 2019. 'The influence of diet on microRNAs that impact cardiovascular disease', Molecules, 24: 1509. DOI: https://doi.org/10.3390/molecules24081509
Leite, Richard D, J Prestes, GB Pereira, GE Shiguemoto, and SEA Perez. 2010. 'Menopause: highlighting the effects of resistance training', International journal of sports medicine, 31: 761-67. DOI: https://doi.org/10.1055/s-0030-1261893
Liou, Chian-Jiun, Xuan-Yu Lai, Ya-Ling Chen, Chia-Ling Wang, Ciao-Han Wei, and Wen-Chung Huang. 2015. 'Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signaling pathway', Evidence-Based Complementary and Alternative Medicine, 2015.  DOI: https://doi.org/10.1155/2015/915467
Liu, Chiung-Ju, and Nancy Latham. 2011. 'Can progressive resistance strength training reduce physical disability in older adults? A meta-analysis study', Disability and rehabilitation, 33: 87-97. DOI: https://doi.org/10.3109/09638288.2010.503835
Liu, Chiung-ju, Deepika M Shiroy, Leah Y Jones, and Daniel O Clark. 2014. 'Systematic review of functional training on muscle strength, physical functioning, and activities of daily living in older adults', European review of aging and physical activity, 11: 95-106. DOI: https://doi.org/10.1007/s11556-014-0144-1
Lou, Zhe, Qiaobei Li, Chunyan Wang, and Yinyan Li. 2022. 'The effects of microRNA-126 reduced inflammation and apoptosis of diabetic nephropathy through PI3K/AKT signalling pathway by VEGF', Archives of physiology and biochemistry, 128: 1265-74. DOI: https://doi.org/10.1080/13813455.2021.1880994
Lunenfeld, Bruno, and Pamela Stratton. 2013. 'The clinical consequences of an ageing world and preventive strategies', Best practice & research Clinical obstetrics & gynaecology, 27: 643-59. DOI: https://doi.org/10.1016/j.bpobgyn.2013.05.005
Madika, Anne-Laure, Phenicia Nasserdine, Sandra Langlet, Charlotte Lecerf, Guillaume Ledieu, Patrick Devos, and Claire Mounier-Vehier. 2019. 'Association between reproductive factors and carotid atherosclerosis in post-menopausal women', Maturitas, 126: 38-44. DOI: https://doi.org/10.1016/j.maturitas.2019.05.004
Massaro, Marika, Egeria Scoditti, Maria Annunziata Carluccio, and Raffaele De Caterina. 2019. 'Oxidative stress and vascular stiffness in hypertension: A renewed interest for antioxidant therapies?', Vascular pharmacology, 116: 45-50. DOI: https://doi.org/10.1016/j.vph.2019.03.002
McKinlay, Sonja M, Donald J Brambilla, and Jennifer G Posner. 1992. 'The normal menopause transition', Maturitas, 14: 103-15.  DOI: https://doi.org/10.1016/0378-5122(92)90003-D
Methenitis, Spyridon. 2018. 'A brief review on concurrent training: from laboratory to the field', Sports, 6: 127. DOI: 10.3390/sports6040127
Montenont, Emilie, Matthew T Rondina, and Robert A Campbell. 2019. 'Altered functions of platelets during aging', Current opinion in hematology, 26: 336.  DOI: https://doi.org/10.1097/MOH.0000000000000530
Parwani, Kirti, and Palash Mandal. 2023. 'Role of advanced glycation end products and insulin resistance in diabetic nephropathy', Archives of physiology and biochemistry, 129: 95-107. DOI: https://doi.org/10.1080/13813455.2021.1880995
Premont, Richard T, James D Reynolds, Rongli Zhang, and Jonathan S Stamler. 2021. 'Red blood cell-mediated S-nitrosohemoglobin-dependent vasodilation: lessons learned from a β-globin Cys93 knock-in mouse', Antioxidants & Redox Signaling, 34: 936-61. DOI: https://doi.org/10.1089/ars.2020.8132
Ren, Shuyue, Peirong Lin, Jingrong Wang, Haoying Yu, Tingting Lv, Lan Sun, and Guanhua Du. 2020. 'Circular RNAs: promising molecular biomarkers of human aging-related diseases via functioning as an miRNA sponge', Molecular Therapy-Methods & Clinical Development, 18: 215-29.  DOI: https://doi.org/10.1016/j.omtm.2020.07.016
Rossi, Fabrício Eduardo, Ana Claudia S Fortaleza, Lucas M Neves, Tiego A Diniz, Marcela R De Castro, Camila Buonani, Jorge Mota, and Ismael F Freitas. 2017. 'Combined training (strength plus aerobic) potentiates a reduction in body fat but only functional training reduced low-density lipoprotein cholesterol in postmenopausal women with a similar training load', Journal of exercise rehabilitation, 13: 322. DOI: https://doi.org/10.12965/jer.1734998.499
Saito, Yuki, Takako S Chikenji, Takashi Matsumura, Masako Nakano, and Mineko Fujimiya. 2020. 'Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors', Nature communications, 11: 889. DOI: https://doi.org/10.1038/s41467-020-14676-4
Sanchis-Gomar, Fabian, Carl J Lavie, Jorge Marín, Carme Perez-Quilis, Thijs MH Eijsvogels, James H O’Keefe, Marco V Perez, and Steven N Blair. 2022. 'Exercise effects on cardiovascular disease: from basic aspects to clinical evidence', Cardiovascular Research, 118: 2253-66. DOI: https://doi.org/10.1093/cvr/cvab237
Shirvani, Hossein, Reza Mirnejad, Mehdi Soleimani, and Ehsan Arabzadeh. 2021. 'Swimming exercise improves gene expression of PPAR-γ and downregulates the overexpression of TLR4, MyD88, IL-6, and TNF-α after high-fat diet in rat skeletal muscle cells', Gene, 775: 145441. DOI: https://doi.org/10.1016/j.gene.2020.145441
Soci, Ursula Paula Renó, Stephano Freitas Soares Melo, João Lucas Penteado Gomes, André Casanova Silveira, Clara Nóbrega, and Edilamar Menezes de Oliveira. 2017. 'Exercise training and epigenetic regulation: multilevel modification and regulation of gene expression', Exercise for Cardiovascular Disease Prevention and Treatment: From Molecular to Clinical, Part 2: 281-322. DOI: https://doi.org/10.1007/978-981-10-4307-9_1
Stenger, Leslie. 2018. 'What is functional/neuromotor fitness?', ACSM's Health & Fitness Journal, 22: 35-43. DOI: https://doi.org/10.1249/FIT.0000000000000430
Tan, DA, and ARB Dayu. 2022. 'Menopausal hormone therapy: why we should no longer be afraid of the breast cancer risk', Climacteric, 25: 362-68. DOI: https://doi.org/10.1080/13697137.2021.1975736
Thijssen, Dick HJ, Mark A Black, Kyra E Pyke, Jaume Padilla, Greg Atkinson, Ryan A Harris, Beth Parker, Michael E Widlansky, Michael E Tschakovsky, and Daniel J Green. 2011. 'Assessment of flow-mediated dilation in humans: a methodological and physiological guideline', American Journal of Physiology-Heart and Circulatory Physiology, 300: H2-H12. DOI: https://doi.org/10.1152/ajpheart.00471.2010
Türkuçar, Serkan, Kaan Yıldız, Tuncay Küme, Ceyhun Açarı, Hatice Adıgüzel Dundar, Balahan Makay, Mustafa Kır, and Erbil Ünsal. 2021. 'Does Familial Mediterranean Fever Provoke Atherosclerosis in Children? Evaluation of Arterial Stiffness and Serum Endocan Levels', Clinical Rheumatology, 40: 4199-206. DOI: https://doi.org/10.1007/s10067-021-05776-8
Wang, An, Bo Sun, Jia Qiu, Shigang Qiao, and Chen Wang. 2016. 'Role of microRNA-1 on fibrosis induced by high glucose cultured cardiac fibroblasts', Chinese Critical Care Medicine: 1113-17. OI: https://doi.org/10.3760/cma.j.issn.2095-4352.2016.12.006
Wang, H-F, Y-Q Wang, L Dou, H-M Gao, B Wang, N Luo, and Y Li. 2019. 'Influences of up-regulation of miR-126 on septic inflammation and prognosis through AKT/Rac1 signaling pathway', European Review for Medical & Pharmacological Sciences, 23. DOI: https://doi.org/10.26355/eurrev_201912_19764
Wang, Shusheng, Arin B Aurora, Brett A Johnson, Xiaoxia Qi, John McAnally, Joseph A Hill, James A Richardson, Rhonda Bassel-Duby, and Eric N Olson. 2008. 'The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis', Developmental cell, 15: 261-71. DOI: https://doi.org/10.1016/j.devcel.2008.07.002
Wilson, Jacob M, Pedro J Marin, Matthew R Rhea, Stephanie MC Wilson, Jeremy P Loenneke, and Jody C Anderson. 2012. 'Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises', The Journal of Strength & Conditioning Research, 26: 2293-307. DOI: https://doi.org/10.1519/JSC.0b013e31823a3e2d
Winkler, Juliane, Abisola Abisoye-Ogunniyan, Kevin J Metcalf, and Zena Werb. 2020. 'Concepts of extracellular matrix remodelling in tumour progression and metastasis', Nature communications, 11: 5120. DOI: https://doi.org/10.1038/s41467-020-18961-w
Wong, Pui-lam, Anis Chaouachi, Karim Chamari, Alexandre Dellal, and Ulrik Wisloff. 2010. 'Effect of preseason concurrent muscular strength and high-intensity interval training in professional soccer players', The Journal of Strength & Conditioning Research, 24: 653-60. DOI: https://doi.org/10.1519/JSC.0b013e3181c06a77
Xiang, Du, Yang Liu, Shujun Zhou, Encheng Zhou, and Yanfeng Wang. 2021. 'Protective effects of estrogen on cardiovascular disease mediated by oxidative stress', Oxidative Medicine and Cellular Longevity, 2021: 1-15. DOI: https://doi.org/10.1155/2021/8817950
Zanetti, Hugo Ribeiro, Alexandre Goncalves, Leandro Teixeira Paranhos Lopes, Edmar Lacerda Mendes, Leonardo Roever, Mario Leon Silva-Vergara, Fernando Freitas Neves, and Elmiro Santos Resende. 2020. 'Effects of exercise training and statin use in people living with human immunodeficiency virus with dyslipidemia', Medicine & Science in Sports & Exercise, 52: 16-24. DOI: https://doi.org/10.1249/MSS.0000000000002248