Effects of Exercise-induced myokines on cardiac function: Muscle– cardiac Crosstalk in health and diseases
محورهای موضوعی : فیزیولوژی ورزشی
1 - Assistant Professor, Department of Physical Education and Sport Sciences, Faculty of Command and Management, Imam Ali military' University, Tehran, Iran
کلید واژه: Exercise, myokines , cardiac function, Muscle, Crosstalk ,
چکیده مقاله :
Recent studies have shown that skeletal muscle serves as a secretory organ that can produce cytokines and other muscle fiber-derived peptides [1]. The contraction of skeletal muscle cells has been found to release humoral factors that regulate metabolic processes [2]. Cytokines and peptides released from skeletal muscle are generally classified as “myokines.” In general, myokines are muscle-derived molecules that perform physiological and pathological functions and maintain systemic homeostasis. Myokines regulate whole body metabolism in an autocrine, paracrine, or hormonal manner [3]. On the one hand, myofiber-induced myokines have positive autocrine and paracrine effects on satellite cell proliferation and muscle hypertrophy [4]. This can provide a feedback loop for the muscles to adapt to exercise training. On the other hand, myokines perform physiological functions by interacting with other distant non-muscular organs at the hormonal level and play an important role in mediating whole-body effects [5]. Emerging evidence suggests that myokines derived from skeletal muscle can improve human health and alleviate many diseases [6]. Numerous studies have shown that muscle mass and function are associated with cardiovascular disease risk [7]. Physical exercise improves cardiovascular health by releasing myokines, which promote the well-known protective effects and functions of the cardiovascular system. Myokines that affect cardiovascular health include dermcidin, follistatin-like 1 (FSTL1), myonectin, apelin, and musclin (Figure 1). Dermcidin secreted by ischemic skeletal muscle may be an important novel myokine that mediates muscle-cardiac cross talk and modulates cardiomyocyte survival and function by controlling cardiomyocyte apoptosis [8]. FSTL1 attenuates neointima formation in response to arterial injury by inhibiting muscle cell proliferation through an AMPK-dependent mechanism [9-11]. Furthermore, FSTL1 promotes endothelial cell function and stimulates revascularization in response to Akt-eNOS-induced ischemic signaling [12]. Abundantly expressed in skeletal muscle tissue, Myonectin is strongly induced in differentiated myotubes and expressed primarily in skeletal muscle. myonectin modulates the response to acute ischemic heart injury and protects the heart from ischemic reperfusion injury by inhibiting apoptosis and inflammatory responses in a mouse exercise model, thus mediating the beneficial effects of exercise on cardiovascular health [13]. Apelin binds to the APJ receptor and acts as an essential mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular disease [14]. Hearts treated with Apelin show increased sensitivity to Ca2+, which may protect against hypertrophy and support cardiac function during the transition to heart failure [14]. In addition, the Apelin/APJ system attenuates cardiac hypertrophy induced by angiotensin II, oxidative stress and exercise [15]. In addition to apelin, muscle binds to natriuretic peptide clearance receptors and is involved in blood pressure regulation [16-19].
Recent studies have shown that skeletal muscle serves as a secretory organ that can produce cytokines and other muscle fiber-derived peptides [1]. The contraction of skeletal muscle cells has been found to release humoral factors that regulate metabolic processes [2]. Cytokines and peptides released from skeletal muscle are generally classified as “myokines.” In general, myokines are muscle-derived molecules that perform physiological and pathological functions and maintain systemic homeostasis. Myokines regulate whole body metabolism in an autocrine, paracrine, or hormonal manner [3]. On the one hand, myofiber-induced myokines have positive autocrine and paracrine effects on satellite cell proliferation and muscle hypertrophy [4]. This can provide a feedback loop for the muscles to adapt to exercise training. On the other hand, myokines perform physiological functions by interacting with other distant non-muscular organs at the hormonal level and play an important role in mediating whole-body effects [5]. Emerging evidence suggests that myokines derived from skeletal muscle can improve human health and alleviate many diseases [6]. Numerous studies have shown that muscle mass and function are associated with cardiovascular disease risk [7]. Physical exercise improves cardiovascular health by releasing myokines, which promote the well-known protective effects and functions of the cardiovascular system. Myokines that affect cardiovascular health include dermcidin, follistatin-like 1 (FSTL1), myonectin, apelin, and musclin (Figure 1). Dermcidin secreted by ischemic skeletal muscle may be an important novel myokine that mediates muscle-cardiac cross talk and modulates cardiomyocyte survival and function by controlling cardiomyocyte apoptosis [8]. FSTL1 attenuates neointima formation in response to arterial injury by inhibiting muscle cell proliferation through an AMPK-dependent mechanism [9-11]. Furthermore, FSTL1 promotes endothelial cell function and stimulates revascularization in response to Akt-eNOS-induced ischemic signaling [12]. Abundantly expressed in skeletal muscle tissue, Myonectin is strongly induced in differentiated myotubes and expressed primarily in skeletal muscle. myonectin modulates the response to acute ischemic heart injury and protects the heart from ischemic reperfusion injury by inhibiting apoptosis and inflammatory responses in a mouse exercise model, thus mediating the beneficial effects of exercise on cardiovascular health [13]. Apelin binds to the APJ receptor and acts as an essential mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular disease [14]. Hearts treated with Apelin show increased sensitivity to Ca2+, which may protect against hypertrophy and support cardiac function during the transition to heart failure [14]. In addition, the Apelin/APJ system attenuates cardiac hypertrophy induced by angiotensin II, oxidative stress and exercise [15]. In addition to apelin, muscle binds to natriuretic peptide clearance receptors and is involved in blood pressure regulation [16-19].
1, Giudice, Jimena, and Joan M. Taylor. "Muscle as a paracrine and endocrine organ." Current opinion in pharmacology 34 (2017): 49-55. https://doi.org/10.1016/j.coph.2017.05.005
2. Mohammadi, S., Rostamkhani, F., Riyahi Malayeri, S. et al. High-intensity interval training with probiotic supplementation decreases gene expression of NF-κβ and CXCL2 in small intestine of rats with steatosis. Sport Sci Health 2021. https://doi.org/10.1007/s11332-021-00829-5.
3. So, Byunghun, et al. "Exercise-induced myokines in health and metabolic diseases." Integrative medicine research 3.4 (2014): 172-179.https://doi.org/10.1016/j.imr.2014.09.007
4. Takhti M, Riyahi Malayeri S, Behdari R. Comparison of two methods of concurrent training and ginger intake on visfatin and metabolic syndrome in overweight women. Razi Journal of Medical Sciences. 2020;27(9):98-111.
5. Huh, Joo Young. "The role of exercise-induced myokines in regulating metabolism." Archives of pharmacal research 41.1 (2018): 14-29.. https://doi. org/10.1007/s12272-017-0994-y
6. Motl, Robert W., and Lara A. Pilutti. "The benefits of exercise training in multiple sclerosis." Nature Reviews Neurology 8.9 (2012): 487-497. https:// doi.org/10.1038/nrneurol.2012.136
7. Riyahi Malayeri S, Azadniya A, Rasaee M J. Effect of eight-week High intensity interval training nd resveratrol intake on serum adiponectin and resistin in type 2 diabetic rats. Ijdld 2019; 18 (1) :8-1. URL: http://ijdld.tums.ac.ir/article-1-5708-en.html.
8. Esposito, Giovanni, et al. "Dermcidin: a skeletal muscle myokine modulating cardiomyocyte survival and infarct size after coronary artery ligation." Cardiovascular research 107.4 (2015): 431-441.. https://doi.org/10.1093/cvr/cvv173
9. Görgens, S. W., Raschke, S., Holven, K. B., Jensen, J., Eckardt, K., & Eckel, J. (2013). Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells. Archives of physiology and biochemistry, 119(2), 75-80.https://doi.org/10.3109/ 13813455.2013.768270
10. Miyabe, Megumi, et al. "Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury." Cardiovascular research 103.1 (2014): 111-120.https://doi.org/10.1093/cvr/cvu105
11Norheim, Frode, et al. "Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training." American Journal of Physiology-Endocrinology and Metabolism 301.5 (2011): E1013-E1021.. https://doi.org/10.1152/ajpendo.00326.2011
12. Ouchi, Noriyuki, et al. "Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism." Journal of Biological Chemistry 283.47 (2008): 32802-32811.. https://doi.org/10. 1074/jbc.M803440200
13. Otaka, Naoya, et al. "Myonectin is an exercise-induced myokine that protects the heart from ischemia-reperfusion injury." Circulation research 123.12 (2018): 1326-1338.https://doi.org/10.1161/CIRCRESAHA. 118.313777
14. Parikh, Victoria N., et al. "Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition." American Journal of Physiology-Heart and Circulatory Physiology 315.2 (2018): H348-H356. https://doi.org/ 10.1152/ajpheart.00693.2017
15. Zhang, Zhen-Zhou, et al. "Apelin is a negative regulator of angiotensin II–mediated adverse myocardial remodeling and dysfunction." Hypertension 70.6 (2017): 1165-1175.. https://doi.org/10.1161/ HYPERTENSIONAHA.117.10156
16. Li, Ying-Xiao, et al. "Role of musclin in the pathogenesis of hypertension in rat." PLoS One 8.8 (2013): e72004.https://doi.org/10.1371/journal.pone. 0072004
17. Lin, Jia-Wei, et al. "Characterization of musclin as a new target for treatment of hypertension." BioMed Research International 2014.1 (2014): 354348.. https:// doi.org/10.1155/2014/354348.
18. Ashtary-Larky D, Lamuchi-Deli N, Kashkooli S, Mombaini D, Alipour M, Khodadadi F, Bagheri R, Dutheil F, Wong A. The effects of exercise training on serum concentrations of chemerin in individuals with overweight and obesity: a systematic review, meta-analysis, and meta-regression of 43 clinical trials. Arch Physiol Biochem. 2023 Oct;129(5):1012-1027. doi: 10.1080/13813455.2021.1892148. Epub 2021 Mar 12. PMID: 33706633.
19. Hedayati S, Riyahi Malayeri S, Hoseini M. The Effect of Eight Weeks of High and Moderate Intensity Interval Training Along with Aloe Vera Consumption on Serum Levels of Chemerin, Glucose and Insulin in Streptozotocin-induced Diabetic Rats: An Experimental Study. JRUMS. 2018; 17 (9) :801-814. URL: http://journal.rums.ac.ir/article-1-4209-fa.html.
Effects of Exercise-induced myokines on cardiac function: Muscle– cardiac Crosstalk in health and diseases
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Journal of Exercise&
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Letter to the Editor |
*Corresponding author: Reza Sabzevari Rad Address: Department of Physical Education and Sport Sciences, Faculty of Command and Management, Imam Ali military' University, Tehran, Iran. Email: sabzevarireza63@yahoo.com · A D: 0000-0003-4410-084 |
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1. Assistant Professor, Department of Physical Education and Sport Sciences, Faculty of Command and Management, Imam Ali military' University, Tehran, Iran.
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Revised: 8 March 2025 Accepted: 9 April 2025
Keywords: Functional Stretching, Extra Functional Stretching, dorsi Flexion, Plantar Flexion. |
Journal of Sports Physiology and Athletic Conditioning Talk |
Journal of Exercise&
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Figure. Myokine with regulatory functions in the heart. Several myokines have been identified in the heart that play a regulatory role. For example, dermcidin modulates cardiomyocyte survival and function by controlling cardiomyocyte apoptosis. FSTL1 impairs neointima formation, supports endothelial cell function and stimulates revascularization. Myonectin is responsible for protecting the heart from ischemia-reperfusion injury. At the same time, Apelin can support the work of the heart and protect against heart enlargement/failure. Musklin is involved in blood pressure regulation.
Abbreviations:
FSTL1 follistatin-like 1
AMPK adenosine monophosphate kinase
eNOS Endothelial nitric oxide synthase
Akt Any agent that inhibits protein kinase B
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References |
12. Ouchi, Noriyuki, et al. "Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism." Journal of Biological Chemistry 283.47 (2008): 32802-32811.. https://doi.org/10. 1074/jbc.M803440200 13. Otaka, Naoya, et al. "Myonectin is an exercise-induced myokine that protects the heart from ischemia-reperfusion injury." Circulation research 123.12 (2018): 1326-1338.https://doi.org/10.1161/CIRCRESAHA. 118.313777 14. Parikh, Victoria N., et al. "Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition." American Journal of Physiology-Heart and Circulatory Physiology 315.2 (2018): H348-H356. https://doi.org/ 10.1152/ajpheart.00693.2017 15. Zhang, Zhen-Zhou, et al. "Apelin is a negative regulator of angiotensin II–mediated adverse myocardial remodeling and dysfunction." Hypertension 70.6 (2017): 1165-1175.. https://doi.org/10.1161/ HYPERTENSIONAHA.117.10156 16. Li, Ying-Xiao, et al. "Role of musclin in the pathogenesis of hypertension in rat." PLoS One 8.8 (2013): e72004.https://doi.org/10.1371/journal.pone. 0072004 17. Lin, Jia-Wei, et al. "Characterization of musclin as a new target for treatment of hypertension." BioMed Research International 2014.1 (2014): 354348.. https:// doi.org/10.1155/2014/354348. 18. Ashtary-Larky D, Lamuchi-Deli N, Kashkooli S, Mombaini D, Alipour M, Khodadadi F, Bagheri R, Dutheil F, Wong A. The effects of exercise training on serum concentrations of chemerin in individuals with overweight and obesity: a systematic review, meta-analysis, and meta-regression of 43 clinical trials. Arch Physiol Biochem. 2023 Oct;129(5):1012-1027. doi: 10.1080/13813455.2021.1892148. Epub 2021 Mar 12. PMID: 33706633. 19. Hedayati S, Riyahi Malayeri S, Hoseini M. The Effect of Eight Weeks of High and Moderate Intensity Interval Training Along with Aloe Vera Consumption on Serum Levels of Chemerin, Glucose and Insulin in Streptozotocin-induced Diabetic Rats: An Experimental Study. JRUMS. 2018; 17 (9) :801-814. URL: http://journal.rums.ac.ir/article-1-4209-fa.html.
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1, Giudice, Jimena, and Joan M. Taylor. "Muscle as a paracrine and endocrine organ." Current opinion in pharmacology 34 (2017): 49-55. https://doi.org/10.1016/j.coph.2017.05.005 2. Mohammadi, S., Rostamkhani, F., Riyahi Malayeri, S. et al. High-intensity interval training with probiotic supplementation decreases gene expression of NF-κβ and CXCL2 in small intestine of rats with steatosis. Sport Sci Health 2021. https://doi.org/10.1007/s11332-021-00829-5. 3. So, Byunghun, et al. "Exercise-induced myokines in health and metabolic diseases." Integrative medicine research 3.4 (2014): 172-179.https://doi.org/10.1016/j.imr.2014.09.007 4. Takhti M, Riyahi Malayeri S, Behdari R. Comparison of two methods of concurrent training and ginger intake on visfatin and metabolic syndrome in overweight women. Razi Journal of Medical Sciences. 2020;27(9):98-111. 5. Huh, Joo Young. "The role of exercise-induced myokines in regulating metabolism." Archives of pharmacal research 41.1 (2018): 14-29.. https://doi. org/10.1007/s12272-017-0994-y 6. Motl, Robert W., and Lara A. Pilutti. "The benefits of exercise training in multiple sclerosis." Nature Reviews Neurology 8.9 (2012): 487-497. https:// doi.org/10.1038/nrneurol.2012.136 7. Riyahi Malayeri S, Azadniya A, Rasaee M J. Effect of eight-week High intensity interval training nd resveratrol intake on serum adiponectin and resistin in type 2 diabetic rats. Ijdld 2019; 18 (1) :8-1. URL: http://ijdld.tums.ac.ir/article-1-5708-en.html. 8. Esposito, Giovanni, et al. "Dermcidin: a skeletal muscle myokine modulating cardiomyocyte survival and infarct size after coronary artery ligation." Cardiovascular research 107.4 (2015): 431-441.. https://doi.org/10.1093/cvr/cvv173 9. Görgens, S. W., Raschke, S., Holven, K. B., Jensen, J., Eckardt, K., & Eckel, J. (2013). Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells. Archives of physiology and biochemistry, 119(2), 75-80.https://doi.org/10.3109/ 13813455.2013.768270 10. Miyabe, Megumi, et al. "Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury." Cardiovascular research 103.1 (2014): 111-120.https://doi.org/10.1093/cvr/cvu105 11Norheim, Frode, et al. "Proteomic identification of secreted proteins from human skeletal muscle cells and expression in response to strength training." American Journal of Physiology-Endocrinology and Metabolism 301.5 (2011): E1013-E1021.. https://doi.org/10.1152/ajpendo.00326.2011
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