Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity

Article


Wang, Linjia, Zhu, Rongxin, Wang, Jiahui, Yu, Siwang, Wang, Jianxiong and Zhang, Ying. 2020. "Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity." Medicine and Science in Sports and Exercise. 52 (8), pp. 1719-1728. https://doi.org/10.1249/MSS.0000000000002312
Article Title

Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity

ERA Journal ID9788
Article CategoryArticle
AuthorsWang, Linjia (Author), Zhu, Rongxin (Author), Wang, Jiahui (Author), Yu, Siwang (Author), Wang, Jianxiong (Author) and Zhang, Ying (Author)
Journal TitleMedicine and Science in Sports and Exercise
Journal Citation52 (8), pp. 1719-1728
Number of Pages10
Year2020
PublisherLippincott Williams & Wilkins
Place of PublicationUnited States
ISSN0195-9131
1530-0315
Digital Object Identifier (DOI)https://doi.org/10.1249/MSS.0000000000002312
Web Address (URL)https://journals.lww.com/acsm-msse/Fulltext/2020/08000/Nrf2_Activation_Enhances_Muscular_MCT1_Expression.9.aspx
Abstract

Introduction
Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate–pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle.

Methods
In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated.

Results
The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline–exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN.

Conclusion
These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.

KeywordsMonocarboxylate Transporter 1; Lactate; Nrf2; Skeletal Muscle; Hypoxic Exercise; Sulforaphane
ANZSRC Field of Research 2020420702. Exercise physiology
Byline AffiliationsBeijing Sport University, China
Shanghai Research Institute of Sports Science, China
Peking University, China
Faculty of Health, Engineering and Sciences
Institution of OriginUniversity of Southern Queensland
Permalink -

https://research.usq.edu.au/item/q5x8z/nrf2-activation-enhances-muscular-mct1-expression-and-hypoxic-exercise-capacity

  • 163
    total views
  • 8
    total downloads
  • 8
    views this month
  • 0
    downloads this month

Export as

Related outputs

Sulforaphane enhances Nrf2-mediated antioxidant responses of skeletal muscle induced by exhaustive exercise in HIIT mice
Wang, Yangwenjie, Xiang, Yang, Wang, Ruiqi, Li, Xiangning, Wang, Jianxiong, Yu, Siwang and Zhang, Ying. 2022. "Sulforaphane enhances Nrf2-mediated antioxidant responses of skeletal muscle induced by exhaustive exercise in HIIT mice." Food Science and Human Wellness. 11 (5), pp. 1355-1361. https://doi.org/10.1016/j.fshw.2022.04.035
Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity
He, Shiyi, Yan, Lu, Zhu, Rongxin, Wei, Hao, Wang, Jianxiong, Zheng, Lan and Zhang, Ying. 2022. "Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity." Life. 12 (8). https://doi.org/10.3390/life12081233
A framework of developing health care application systems using 6LoWPAN based wireless sensor networks
Zhang, Zhongwei, Wang, Jianxiong and Hu, Xiaohua. 2020. "A framework of developing health care application systems using 6LoWPAN based wireless sensor networks." Ever, Enver and Al-Turjman, Fadi (ed.) 1st EAI International Conference on Forthcoming Networks and Sustainability in the IoT Era. Turkey 01 - 02 Oct 2020 Cham, Switzerland. https://doi.org/10.1007/978-3-030-69431-9_12
High-intensity interval training and moderate-intensity continuous training attenuate oxidative damage and promote myokine response in the skeletal muscle of ApoE KO mice on high-fat diet
Wang, Linjia, Lavier, Jessica, Hua, Weicheng, Wang, Yangwenjie, Gong, Lijing, Wei, Hao, Wang, Jianxiong, Pellegrin, Maxime, Millet, Gregoire P. and Zhang, Ying. 2021. "High-intensity interval training and moderate-intensity continuous training attenuate oxidative damage and promote myokine response in the skeletal muscle of ApoE KO mice on high-fat diet." Antioxidants. 10 (7). https://doi.org/10.3390/antiox10070992
Academic achievement and student satisfaction: moving anatomy and physiology teaching online
Chruscik, Anna, Windus, Louisa, Wang, Jianxiong, Kauter, Kate and Whiteside, Eliza. 2020. "Academic achievement and student satisfaction: moving anatomy and physiology teaching online." 2020 Australian Conference on Science and Mathematics Education (formerly UniServe Science Conference). Online 30 Sep - 02 Oct 2020 Australia.
Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2
Wang, Linjia, Yang, Simin, Yan, Lu, Wei, Hao, Wang, Jianxiong, Yu, Siwang, Kong, Ah-Ng Tony and Zhang, Ying. 2019. "Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2." Journal of Applied Physiology. 127, pp. 1267-1277. https://doi.org/10.1152/japplphysiol.00347.2019
Aerobic exercise training at maximal fat oxidation intensity improves body composition, glycemic control, and physical capacity in older people with type 2 diabetes
Jiang, Yan, Tan, Sijie, Wang, Zhaoyu, Guo, Zhen, Li, Qingwen and Wang, Jianxiong. 2020. "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 and Fitness. 18 (1), pp. 7-13. https://doi.org/10.1016/j.jesf.2019.08.003
MiR-340-5p: a potential direct regulator of Nrf2 expression in post-exercise skeletal muscle of mice
Mei, Tao, Liu, Yujia, Wang, Jianxiong and Zhang, Ying. 2019. "MiR-340-5p: a potential direct regulator of Nrf2 expression in post-exercise skeletal muscle of mice." Molecular Medicine Reports. 19 (2), pp. 1340-1348. https://doi.org/10.3892/mmr.2018.9762
Exercise training at maximal fat oxidation intensity for overweight or obese older women: a randomized study
Cao, Liquan, Jiang, Yan, Li, Qingwen, Wang, Jianxiong and Tan, Sijie. 2019. "Exercise training at maximal fat oxidation intensity for overweight or obese older women: a randomized study." Journal of Sports Science and Medicine. 18, pp. 413-418.
Soccer training: an effective exercise mode to prevent and treat childhood obesity?
Cao, Liquan, Guo, Zhen, Tan, Sijie and Wang, Jianxiong. 2019. "Soccer training: an effective exercise mode to prevent and treat childhood obesity?" Biomedical Journal of Scientific and Technical Research. 16 (3). https://doi.org/10.26717/BJSTR.2019.16.002844
Hypoxia exposure alleviates impaired muscular metabolism, glucose tolerance, and aerobic capacity in apelin-knockout mice
He, Shiyi, Li, Junping, Wang, Jianxiong and Zhang, Ying. 2019. "Hypoxia exposure alleviates impaired muscular metabolism, glucose tolerance, and aerobic capacity in apelin-knockout mice." FEBS Open Bio. 9 (3), pp. 498-509. https://doi.org/10.1002/2211-5463.12587
Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle
Ji, Weixiu, Wang, Linjia, He, Shiyi, Yan, Lu, Li, Tieying, Wang, Jianxiong, Kong, Ah-Ng Tony, Yu, Siwang and Zhang, Ying. 2018. "Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle." PLoS One. 13 (12), pp. 1-15. https://doi.org/10.1371/journal.pone.0208474
Negative correlation between core muscle function and body composition in young people aged 18-30 years
Rasif, Hazheer and Wang, Jianxiong. 2017. "Negative correlation between core muscle function and body composition in young people aged 18-30 years." International Journal of Sport, Exercise and Health Research. 1 (1), pp. 49-53.
Exercise training at maximal fat oxidation intensity for older women with type 2 diabetes
Tan, Sijie, Du, Ping, Zhao, Wanting, Pang, Jiaqi and Wang, Jianxiong. 2018. "Exercise training at maximal fat oxidation intensity for older women with type 2 diabetes." International Journal of Sports Medicine. 39 (5), pp. 374-381. https://doi.org/10.1055/a-0573-1509
Supervised physical training improves fine motor skills of 5-year-old children
Qi, Yugang, Tan, Sijie, Sui, Mingyang and Wang, Jianxiong. 2018. "Supervised physical training improves fine motor skills of 5-year-old children." Brazilian Journal of Sports Medicine. 24 (1), pp. 9-12. https://doi.org/10.1590/1517-869220182401177117
Few-layer graphdiyne nanosheets applied for multiplexed real-time DNA detection
Parvin, Nargish, Jin, Quan, Wei, Yanze, Yu, Ranbo, Zheng, Bing, Huang, Ling, Zhang, Ying, Wang, Lianhui, Zhang, Hua, Gao, Mingyuan, Zhao, Huijun, Hu, Wenping, Li, Yuliang and Wang, Dan. 2017. "Few-layer graphdiyne nanosheets applied for multiplexed real-time DNA detection." Advanced Materials. 29 (18), pp. 1-7. https://doi.org/10.1002/adma.201606755
Recreational football training improved health-related physical fitness in 9- to 10-year-old boys
Wang, Jin, Cao, Liquan, Xie, Pengfei and Wang, Jianxiong. 2018. "Recreational football training improved health-related physical fitness in 9- to 10-year-old boys." The Journal of Sports Medicine and Physical Fitness. 58 (3), pp. 326-331. https://doi.org/10.23736/S0022-4707.16.06620-2
Exercise training improved body composition, cardiovascular function, and physical fitness of 5-year-old children with obesity or normal body mass
Tan, Sijie, Chen, Cheng, Sui, Mingyang, Xue, Lunan and Wang, Jianxiong. 2017. "Exercise training improved body composition, cardiovascular function, and physical fitness of 5-year-old children with obesity or normal body mass." Pediatric Exercise Science. 29 (2), pp. 245-253. https://doi.org/10.1123/pes.2016-0107
Hypoxic exercise training promotes apelin/APJ expression in skeletal muscles of high fat diet-induced obese mice
Ji, Weixiu, Gong, Lijing, Wang, Jianxiong, He, Hui and Zhang, Ying. 2017. "Hypoxic exercise training promotes apelin/APJ expression in skeletal muscles of high fat diet-induced obese mice." Protein and Peptide Letters: international journal for rapid publication of short papers in protein and peptide science. 24 (1), pp. 64-70. https://doi.org/10.2174/0929866524666161111111726
Reliability of functional capacity measurements for peripheral arterial disease (PAD) patients
Wang, J., Zhou, S., Bronks, R., Graham, J. and Myers, S.. 2002. "Reliability of functional capacity measurements for peripheral arterial disease (PAD) patients ." Journal of Science and Medicine in Sport. 5 (4 (Supplement 1)), pp. 127-127. https://doi.org/10.1016/S1440-2440(02)80268-7
Treatment of peripheral arterial disease with percutaneous transluminal angioplasty or supervised exercise training.
Wang, J, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2006. "Treatment of peripheral arterial disease with percutaneous transluminal angioplasty or supervised exercise training. " 5th annual conference for Society of Chinese Scholars on Exercise Physiology and Fitness. Tianjin, China 25 - 27 Oct 2006
Supervised exercise rehabilitation in chronic obstructive pulmonary disease
Wang, Jianxiong, Graham, B., Burton, D. and Car, G.. 2006. "Supervised exercise rehabilitation in chronic obstructive pulmonary disease." 5th annual conference for Society of Chinese Scholars on Exercise Physiology and Fitness. Tianjin, China 25 - 27 Oct 2006
Responses of calf muscle isokinetic strength and endurance to supervised treadmill-walking training in patients with peripheral arterial disease
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2004. "Responses of calf muscle isokinetic strength and endurance to supervised treadmill-walking training in patients with peripheral arterial disease ." 1st Congress of the Australian Association of Exercise and Sport Science(AAESS). Brisbane, Australia 14 - 16 Apr 2004
A new role of home-based exercise program in peripheral arterial disease patients
Wang, J., Zhou, S., Bronks, R., Graham, J., Myers, S. and Silk, A.. 2004. "A new role of home-based exercise program in peripheral arterial disease patients." Australian Conference of Science and Medicine in Sport (2004). Alice Springs, Australia 06 - 09 Oct 2004 Australia. https://doi.org/10.1016/S1440-2440(04)80178-6
Effects of four weeks of supplementation with coenzyme Q10 on aerobic power and exercise economy
Zhou, Shi, Zhang, Yong, Davie, Allan, Marshall-Gradisnik, Sonya M., Wang, Jianxion, Hu, Hui and Brushett, Don J.. 2003. "Effects of four weeks of supplementation with coenzyme Q10 on aerobic power and exercise economy." The 2nd annual conference of the Society of Chinese Scholars on Exercise Physiology and Fitness. Macau, China 24 - 27 Nov 2003
Exercise training at the intensity of maximal fat oxidation in obese boys
Tan, Sijie, Wang, Jianxiong and Cao, Liquan. 2016. "Exercise training at the intensity of maximal fat oxidation in obese boys." Applied Physiology, Nutrition and Metabolism. 41 (1), pp. 49-54. https://doi.org/10.1139/apnm-2015-0174
Effects of HIF-1α on ERRα/γ protein expression in mouse skeletal muscle
Zhang, Ying, Ji, Weixiu, Zhang, Lianfeng, Liu, Sixue, Liu, Gang and Wang, Jianxiong. 2015. "Effects of HIF-1α on ERRα/γ protein expression in mouse skeletal muscle." Edorium Journal of Biomedical Technology. 1, pp. 4-10.
Exercise training at the maximal fat oxidation intensity improved health-related physical fitness in overweight middle-aged women
Wang, Jianxiong, Tan, Sijie and Cao, Liquan. 2015. "Exercise training at the maximal fat oxidation intensity improved health-related physical fitness in overweight middle-aged women." Journal of Exercise Science and Fitness. 13 (2), pp. 111-116. https://doi.org/10.1016/j.jesf.2015.08.003
Effects of different exercise durations on Keap1-Nrf2-ARE pathway activation in mouse skeletal muscle
Li, Tieying, He, Sheyi, Liu, Sixue, Kong, Zhenxing, Wang, Jianxiong and Zhang, Ying. 2015. "Effects of different exercise durations on Keap1-Nrf2-ARE pathway activation in mouse skeletal muscle." Free Radical Research. 49 (10), pp. 1269-1274. https://doi.org/10.3109/10715762.2015.1066784
Establishment of the prediction equations of 1RM skeletal muscle strength in 60- to 75-year-old Chinese men and women
Tan, Sijie, Wang, Jianxiong and Liu, Shanshan. 2015. "Establishment of the prediction equations of 1RM skeletal muscle strength in 60- to 75-year-old Chinese men and women." Journal of Aging and Physical Activity. 23 (4), pp. 640-646. https://doi.org/10.1123/japa.2014-0103
Positive effect of exercise training at maximal fat oxidation intensity on body composition and lipid metabolism in overweight middle-aged women
Tan, Sijie, Wang, Jianxiong, Cao, Liquan, Guo, Zhen and Wang, Yuan. 2016. "Positive effect of exercise training at maximal fat oxidation intensity on body composition and lipid metabolism in overweight middle-aged women ." Clinical Physiology and Functional Imaging. 36 (3), pp. 225-230. https://doi.org/10.1111/cpf.12217
PPARα protein expression was increased by four weeks of intermittent hypoxic training via AMPKα2-dependent manner in mouse skeletal muscle
Li, Ge, Wang, Jianxiong, Ye, Jianping, Zhang, Yimin and Zhang, Ying. 2015. "PPARα protein expression was increased by four weeks of intermittent hypoxic training via AMPKα2-dependent manner in mouse skeletal muscle." PLoS One. 10 (4), p. e0122593. https://doi.org/10.1371/journal.pone.0122593
Associations between objectively measured physical activity, cardiorespiratory fitness and risk factors for metabolic syndrome in 12-to 15-year-old Tianjin city children
Tan, Sijie, Wang, Jianxiong, Zhang, Yibing and Zhang, Chen. 2015. "Associations between objectively measured physical activity, cardiorespiratory fitness and risk factors for metabolic syndrome in 12-to 15-year-old Tianjin city children." Health Education Journal. 74 (4), pp. 403-410. https://doi.org/10.1177/0017896914541556
Site-specific relationship between bone mineral density and muscle strength or endurance in elderly men
Wang, Jianxiong, Tan, Sijie and Cao, Liquan. 2014. "Site-specific relationship between bone mineral density and muscle strength or endurance in elderly men." Asian Journal of Exercise and Sports Science. 11 (2), pp. 36-45.
12-week exercise training improved the treadmill walking capacity, peak oxygen uptake, and walking economy of elder claudicants
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen P.. 2003. "12-week exercise training improved the treadmill walking capacity, peak oxygen uptake, and walking economy of elder claudicants." Green, Anita and Brown, Wendy (ed.) 2003 Australian Conference of Science and Medicine in Sport and 3rd National Sports Injury Prevention Conference: Tackling the Barriers to Performance and Participation. Canberra, Australia 25 - 28 Oct 2003 Canberra, Australia. https://doi.org/10.1016/S1440-2440(03)80312-2
Investigation of core muscle function through electromyography activities in healthy young men
Tan, Sijie, Cao, Liquan, Schoenfisch, Whitney and Wang, Jianxiong. 2013. "Investigation of core muscle function through electromyography activities in healthy young men." Journal of Exercise Physiology. 16 (1), pp. 45-52.
Semisolid processing technology
Xie, Shuisheng, Li, Xinggang, Wang, Hao and Zhang, Ying. 2012. Semisolid processing technology. Beijing, China. Metallurgical Industry Press.
Endurance exercise in a rat model of metabolic syndrome
Cameron, Isabelle, Alam, Mohammed Ashraful, Wang, Jianxiong and Brown, Lindsay. 2012. "Endurance exercise in a rat model of metabolic syndrome." Canadian Journal of Physiology and Pharmacology. 90 (11), pp. 1490-1497. https://doi.org/10.1139/y2012-097
Effects of supervised exercise training at the intensity of maximal fat oxidation in overweight young women
Tan, Sijie, Wang, Xue and Wang, Jianxiong. 2012. "Effects of supervised exercise training at the intensity of maximal fat oxidation in overweight young women." Journal of Exercise Science and Fitness. 10 (2), pp. 64-69. https://doi.org/10.1016/j.jesf.2012.10.002
High intensity interval exercise training in overweight young women
Sijie, T., Hainai, Y., Fengying, Y. and Wang, Jianxiong. 2012. "High intensity interval exercise training in overweight young women ." The Journal of Sports Medicine and Physical Fitness. 52 (3), pp. 255-262.
Effects of six months of combined aerobic and resistance training for elderly patients with a long history of type 2 diabetes
Tan, Sijie, Li, Wei and Wang, Jianxiong. 2012. "Effects of six months of combined aerobic and resistance training for elderly patients with a long history of type 2 diabetes ." Journal of Sports Science and Medicine. 11 (3), pp. 495-501.
Effect of exercise training on fibrinolytic function in individuals with peripheral arterial disease (abstract).
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2007. "Effect of exercise training on fibrinolytic function in individuals with peripheral arterial disease (abstract). " Journal of Science and Medicine in Sport. 10 (Supplement), p. 81. https://doi.org/10.1016/S1440-2440(07)70238-4
Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus
Liu, Guang B., Zhang, Ying, Pettigrew, John D., Xu, Wei F. and Li, Chao-Yi. 2003. "Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus." Brain Research. 985 (1), pp. 13-20. https://doi.org/10.1016/S0006-8993(03)03049-X
Physical training of 9- to 10-year-old children with obesity to lactate threshold intensity
Tan, Sijie, Yang, Chunhua and Wang, Jianxiong. 2010. "Physical training of 9- to 10-year-old children with obesity to lactate threshold intensity." Pediatric Exercise Science. 22 (3), pp. 477-485.
Effects of supervised treadmill-walking training on calf muscle capillarization in patients with intermittent claudication
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2009. "Effects of supervised treadmill-walking training on calf muscle capillarization in patients with intermittent claudication." Angiology. 60 (1), pp. 36-41. https://doi.org/10.1177/0003319708317337
Supervised and home-based exercise training for patients with intermittent claudication
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2008. "Supervised and home-based exercise training for patients with intermittent claudication." International Journal of Angiology. 17 (3), pp. 137-140.
Muscle and plasma coenzyme Q10 concentration, aerobic power and exercise economy of healthy men in response to four weeks of supplementation
Zhou, Shi, Zhang, Yong, Davie, A., Marshall-Gradisnik, S., Hu, H., Wang, Jianxiong and Brushett, D.. 2005. "Muscle and plasma coenzyme Q10 concentration, aerobic power and exercise economy of healthy men in response to four weeks of supplementation ." The Journal of Sports Medicine and Physical Fitness. 45 (3), pp. 337-346.
Reciprocal interaction between three areas of the visual cortex of the cat revealed with optical imaging of intrinsic signals
Liu, Guang B., Zhang, Ying, Li, Chao-Yi and Pettigrew, John D.. 2003. "Reciprocal interaction between three areas of the visual cortex of the cat revealed with optical imaging of intrinsic signals." Australian Neuroscience Society 23rd Annual Meeting . Adelaide, Australia 28 - 31 Jan 2003 Adelaide.
Supervised exercise training combined with ginkgo biloba treatment for patients with peripheral arterial disease
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2007. "Supervised exercise training combined with ginkgo biloba treatment for patients with peripheral arterial disease." Clinical Rehabilitation. 21 (7), pp. 579-586. https://doi.org/10.1177/0269215507075205
Effect of supervised treadmill-walking training on strength and endurance of the calf muscles of individuals with peripheral arterial disease
Wang, Jianxiong, Zhou, Shi, Bronks, Roger, Graham, John and Myers, Stephen. 2006. "Effect of supervised treadmill-walking training on strength and endurance of the calf muscles of individuals with peripheral arterial disease." Clinical Journal of Sport Medicine. 16 (5), pp. 397-400. https://doi.org/10.1097/01.jsm.0000244604.70542.b2