Editorial For reprint orders, please contact: [email protected]
Potential biomarkers of skeletal muscle damage “
As the health of skeletal muscle is vitally important to both our physical and etabolic well-being, understanding the scope of damaging insults to skeletal m muscle … can guide therapeutic choices and improve the overall quality of life for those affected.
”
Why do we need muscle damage markers? Skeletal muscle is remarkably resilient, providing a lifetime of adaptation to stimuli (including hypertrophy with resistance activity), and repair from minor ‘exertional trauma’, myopathy or major damage [1] . As the health of skeletal muscle is vitally important to both our physical and metabolic well-being, understanding the scope of damaging insults to skeletal muscle (e.g., statin myopathy) can guide therapeutic choices and improve the overall quality of life for those affected. While the need for myocardial muscle damage biomarkers is apparent, the obvious question is “why do I need to assess skeletal muscle damage with a biomarker? I can feel when my muscles are damaged.” In contrast to cutaneous pain, muscle nociceptor stimulation is processed differently by the CNS. In particular, pain signals from muscle have a special relay in the mesencephalon, and are more strongly inhibited by descending pain-modulating pathways than cutaneous pain signals [2] . Ultimately, this means that unlike cutaneous pain, which feels ‘sharp and prickling’, muscle pain is perceived as a cramping, aching pain; one that is difficult to localize as it exhibits referral to other deep somatic tissues [2] . Thus, perceived pain from muscle injury is highly variable (based on the individual degree of inhibitory modulation) and is not often limiting for necessary activity. From the perspective of a health professional, this makes understanding muscle pain and its impact on the patient’s well-being exceptionally difficult. From a researcher’s perspective, identifying how much damage has been cre-
10.2217/BMM.13.163 © 2014 Future Medicine Ltd
ated with an experimental paradigm (e.g., eccentric or resistance exercise) is challenging, and often relies on questionnaire-based assessment of the muscle damage, perceived as muscle soreness. What markers have historically been used? Serum creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH) have been the standard biomarkers of muscle damage for a number of years. Creatine kinase
Creatine kinase is an enzyme that catalyzes the reversible phosphorylation of creatine to phosphocreatine, and of ADP to ATP [3] . Elevated levels of CK, measured in blood serum, are closely associated with muscle cell damage and muscle-related disease [3,4] . The degree of serum CK elevation can be helpful in differentiating different forms of muscular dystrophy, however, may not be elevated in some myopathies, may display variable expression in each stage of the disorder, and can be lowered as a result of factors such as profound muscle wasting [5] . Additionally, differences in both efflux and basal levels of CK have been shown as a result of gender [6] , athletic ability, type, intensity and duration of exercise [3] , ethnicity [7] , alcohol consumption [8] and prescription drugs such as statins [9] , indicating the contribution of a broad spectrum of factors to elevations in serum CK levels. While some of the aforementioned sources of serum CK may be accounted for by actual muscle damage, others cannot, and this variability makes it very difficult to establish a baseline CK concentration for the indication and diagnosis of
Biomarkers Med. (2014) 8(3), 375–378
Irena A Rebalka Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada
Thomas J Hawke Author for correspondence: Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada Tel.: +1 905 525 9140 ext. 22372; [email protected]
part of
ISSN 1752-0363
375
Editorial Rebalka & Hawke muscle damage and myopathy. Observing high serum CK levels may not be diagnostic in itself but will lead to the conduction of other tests in order to adequately identify myopathy and degree of muscle damage. Myoglobin
Myoglobin is a monomeric cytoplasmic hemoprotein that is expressed exclusively in cardiac myocytes and oxidative skeletal muscle fibers. A simple urinalysis is able to reveal circulating levels of myoglobin (Mb). Circulating Mb is absent or present in very low concentrations in individuals without muscle damage therefore, presence in the urine may indicate muscle damage or myocardial infarction [10] . Mb is a rapid indicator of muscle damage, appearing in the urine 30 min after exertion or injury [11] , and can remain increased in circulation for up to five days post-injury [12] . Although sample collection is very simple, improper sample preparation can cause inaccurate results of Mb concentration. Mb deteriorates rapidly in urine, and its stability can be affected by the pH and temperature of the sample [10] .
• Be increased in a manner that directly correlates with the degree of injury; • Would have a consistent temporal pattern of expression in response to injury; • Be detected in a blood or other accessible body fluid-based assay system. Novel biomarkers to consider? Novel biochemical markers, such as the candidates identified below, are receiving attention for their high sensitivity and/or temporal clarity. We acknowledge that as large-scale proteomics ana-lysis becomes more commonplace, the number of biomarker candidates will expand considerably. Xin
What are the ideal attributes of a muscle damage biomarker? An ideal biomarker of skeletal muscle damage would demonstrate the following characteristics:
Xin, a cytoskeletal adapter protein, was recently identified as a novel biomarker of skeletal muscle damage [14] . Although undetectable within the belly of uninjured skeletal muscle, Xin expression increases with damage severity in a highly correlated manner (regardless whether the damage is a result of myopathy or eccentric exercise in healthy individuals). What’s more, it has been found that Xin expression following acute injury consistently peaked at 12 h postinjury at the mRNA level [15] , and 24 h postinjury at the protein level [16] . While many of the biomarkers noted are found in both cardiac and skeletal muscle (striated), Xin isoforms are differentially expressed (isoform A is predominant in cardiac and isoform B in skeletal muscle) allowing for distinction between damage in these two tissues. If Xin is indeed an ideal biomarker, future work will elucidate the expression profile of Xin within the serum, and determine whether the tight temporal and damage-severity expression patterns still exist.
• Be an exclusive product of skeletal muscle;
Troponin
• Be expressed at minimal levels in an undamaged sample. This feature is of vital importance as baseline readings of muscle damage markers (i.e., measures taken when muscle is healthy and undamaged) are often unknown. A diagnostic tool where a measurable increase in biomarker content is consistent with muscle damage will allow any clinician/researcher to note damage without knowing the baseline biomarker values of the affected individual;
Serum troponin levels have been used for assessment of cardiomyocyte injury and skeletal muscle damage for a number of years [3] . Like Xin, troponin has tissue-specific isoforms allowing distinction between cardiac and skeletal muscle damage (a feature critical if one were interested in identifying cardiomyocyte damage in persons with myopathy). What may make skeletal muscle troponin (sTnI) an interesting biomarker to pursue is that sTnI exists in two isoforms, slow (ssTnI) and fast (fsTnI), corresponding to slowand fast-twitch muscles, respectively. As a general
Lactate dehydrogenase
LDH is an enzyme responsible for the reversible conversion of pyruvate to lactate. LDH is extruded into the circulation from cells as a result of muscle damage, but like other biomarkers, has a notable degree of interperson variability [3] and the detection levels are much lower than that of serum CK [13] . Though CK, myoglobin and LDH levels can be measured without invasive techniques such as a muscle biopsy, a number of factors contribute to their variability in circulating levels at rest, and in their expression postdamage, limiting the viability of their results.
376
• Be increased in a consistent manner, regardless of the type of muscle damage (trauma vs myopathy for example);
Biomarkers Med. (2014) 8(3)
future science group
Potential biomarkers of skeletal muscle damage
damage biomarker, the use of sTnI is hampered by the disparity [17] ; however, this dichotomy may prove useful if one were to investigate disease or injury states that specifically target fast- or slow-twitch muscle fibers [17–19] . miRNAs
The recent emergence of miRNAs has garnered significant attention in both the world of basic science, and the area of muscle damage biomarkers. These endogenous, small noncoding RNAs may prove useful as muscle damage biomarkers due to their size, tissue-specificity and relative abundance and stability in the plasma. Of particular interest is the work of Laterza and colleagues [20] , who demonstrated that plasma miR133a levels served as a very sensitive diagnostic measure for detecting damage induced by skeletal muscle toxicants. The authors noted that the sensitivity of plasma miR133a was much greater than that of CK, which was only slightly elevated in one rodent following this type of injury. Furthermore, plasma miR133a levels were not elevated when liver was damaged by toxin injection, indicating tissue specificity [20] . References 1
Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J. Appl. Physiol. 91(2), 534–551 (2001).
2
Mense S. The pathogenesis of muscle pain. Curr. Pain Headache Rep. 7(6), 419–425 (2003).
3
Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage. Clin. Chem. Lab. Med. 48(6), 757–767 (2010).
4
Pearce JM, Pennington RJ. Walton JN. Serum enzyme studies in muscle disease. II. Serum creatine kinase activity in muscular dystrophy and in other myopathic and neuropathic disorders. J. Neurol. Neurosurg. Psychiatry 27(3), 96–99 (1964).
5
6
7
8
Swaiman K, Sandler B. The use of serum creatine phosphokinase and other serum enzymes in the diagnosis of progressive muscular dystrophy. J. Pediatr. 63(6), 1116–1119 (1963). Amelink GJ, Koot RW, Erich WB, Van Gijn J, Bär PR. Sexlinked variation in creatine kinase release, and its dependence on oestradiol, can be demonstrated in an in-vitro rat skeletal muscle preparation. Acta Physiologica Scandinavica 138(2), 115–124 (1990). Wong ET, Cobb C, Umehara MK et al. Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. Am. J. Clin. Pathol. 79(5), 582–586 (1983). Spargo E. The acute effects of alcohol on plasma creatine kinase (CK) activity in the rat. J. Neurol. Sci. 63(3), 307–316 (1984).
future science group
Editorial
Future studies will help to elucidate whether miRNA expression is a direct or indirect consequence of muscle damage. Additionally, future studies are needed to determine whether expression following various forms of muscle damage follows a specific temporal pattern. Skeletal muscle damage biomarkers are critical tools for healthcare professionals and researchers alike. Whether it be in clinical trials, research studies or exercise therapy prescriptions, the use of these biomarkers will present a sensitive and reliable index of the degree of muscle injury so the best next steps may be made. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. 9
Dale KM, White CM, Henyan NN, Kluger J, Coleman CI. Impact of statin dosing intensity on transaminase and creatine kinase. Am. J. Med. 120(8), 706–712 (2007).
10
Chen-Levy Z, Wener MH, Toivola B, Daum P, Reyes M, Fine JS. Factors affecting urinary myoglobin stability in vitro. Am. J. Clin. Pathol. 123(3), 432–438 (2005).
11
Ascensao A, Rebelo A, Oliveira E, Marques F, Pereira L, Magalhaes J. Biochemical impact of a soccer match – analysis of oxidative stress and muscle damage markers throughout recovery. Clin. Biochem. 41(10), 841–851 (2008).
12
Neubauer O, König D, Wagner KH. Recovery after an Ironman triathlon: sustained inflammatory responses and muscular stress. Eur. J. Appl. Physiol. 104(3), 417–426 (2008).
13
Bessa A, Oliveira VN, De Agostini GG et al. Exercise intensity and recovery: Biomarkers of injury, inflammation and oxidative stress. J. Strength Cond. Res. doi:10.1519/ JSC.0b013e31828f1ee9 (2013) (Epub ahead of print).
14
Nilsson MI, Nissar AA, Al-Sajee D et al. Xin is a marker of skeletal muscle damage severity in myopathies. Am. J. Pathol. 183(6), 1703–1709 (2013).
15
Hawke TJ, Atkinson DJ, Kanatous SB, Van der Ven PFM, Goetsch SC, Garry DJ. Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 293(5), C1636–C1644 (2007).
16
Nissar AA, Zemanek B, Labatia R et al. Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation? Am. J. Physiol. Cell Physiol. 302(1), C220–C227 (2012).
17
Chapman DW, Simpson JA, Iscoe S, Robins T, Nosaka K. Changes in serum fast and slow skeletal troponin I
www.futuremedicine.com
377
Editorial Rebalka & Hawke concentration following maximal eccentric contractions. J. Sci. Med. Sport 16(1), 82–85 (2013). 18
378
Gehrig SM, Koopman R, Naim T, Tjoakarfa C, Lynch GS. Making fast-twitch dystrophic muscles bigger protects them from contraction injury and attenuates the dystrophic pathology. Am. J. Pathol. 176(1), 29–33 (2010).
Biomarkers Med. (2014) 8(3)
19
Vijayan K, Thompson JL, Riley DA. Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles. J. Appl. Physiol. 85(3), 1017–1023 (1998).
20
Laterza OF, Lim L, Garrett-Engele PW, Vlasakova K, Muniappa N, Tanaka WK. Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin. Chem. 55(11), 1977–1983 (2009).
future science group
Potential biomarkers of skeletal muscle damage “
As the health of skeletal muscle is vitally important to both our physical and etabolic well-being, understanding the scope of damaging insults to skeletal m muscle … can guide therapeutic choices and improve the overall quality of life for those affected.
”
Why do we need muscle damage markers? Skeletal muscle is remarkably resilient, providing a lifetime of adaptation to stimuli (including hypertrophy with resistance activity), and repair from minor ‘exertional trauma’, myopathy or major damage [1] . As the health of skeletal muscle is vitally important to both our physical and metabolic well-being, understanding the scope of damaging insults to skeletal muscle (e.g., statin myopathy) can guide therapeutic choices and improve the overall quality of life for those affected. While the need for myocardial muscle damage biomarkers is apparent, the obvious question is “why do I need to assess skeletal muscle damage with a biomarker? I can feel when my muscles are damaged.” In contrast to cutaneous pain, muscle nociceptor stimulation is processed differently by the CNS. In particular, pain signals from muscle have a special relay in the mesencephalon, and are more strongly inhibited by descending pain-modulating pathways than cutaneous pain signals [2] . Ultimately, this means that unlike cutaneous pain, which feels ‘sharp and prickling’, muscle pain is perceived as a cramping, aching pain; one that is difficult to localize as it exhibits referral to other deep somatic tissues [2] . Thus, perceived pain from muscle injury is highly variable (based on the individual degree of inhibitory modulation) and is not often limiting for necessary activity. From the perspective of a health professional, this makes understanding muscle pain and its impact on the patient’s well-being exceptionally difficult. From a researcher’s perspective, identifying how much damage has been cre-
10.2217/BMM.13.163 © 2014 Future Medicine Ltd
ated with an experimental paradigm (e.g., eccentric or resistance exercise) is challenging, and often relies on questionnaire-based assessment of the muscle damage, perceived as muscle soreness. What markers have historically been used? Serum creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH) have been the standard biomarkers of muscle damage for a number of years. Creatine kinase
Creatine kinase is an enzyme that catalyzes the reversible phosphorylation of creatine to phosphocreatine, and of ADP to ATP [3] . Elevated levels of CK, measured in blood serum, are closely associated with muscle cell damage and muscle-related disease [3,4] . The degree of serum CK elevation can be helpful in differentiating different forms of muscular dystrophy, however, may not be elevated in some myopathies, may display variable expression in each stage of the disorder, and can be lowered as a result of factors such as profound muscle wasting [5] . Additionally, differences in both efflux and basal levels of CK have been shown as a result of gender [6] , athletic ability, type, intensity and duration of exercise [3] , ethnicity [7] , alcohol consumption [8] and prescription drugs such as statins [9] , indicating the contribution of a broad spectrum of factors to elevations in serum CK levels. While some of the aforementioned sources of serum CK may be accounted for by actual muscle damage, others cannot, and this variability makes it very difficult to establish a baseline CK concentration for the indication and diagnosis of
Biomarkers Med. (2014) 8(3), 375–378
Irena A Rebalka Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada
Thomas J Hawke Author for correspondence: Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada Tel.: +1 905 525 9140 ext. 22372; [email protected]
part of
ISSN 1752-0363
375
Editorial Rebalka & Hawke muscle damage and myopathy. Observing high serum CK levels may not be diagnostic in itself but will lead to the conduction of other tests in order to adequately identify myopathy and degree of muscle damage. Myoglobin
Myoglobin is a monomeric cytoplasmic hemoprotein that is expressed exclusively in cardiac myocytes and oxidative skeletal muscle fibers. A simple urinalysis is able to reveal circulating levels of myoglobin (Mb). Circulating Mb is absent or present in very low concentrations in individuals without muscle damage therefore, presence in the urine may indicate muscle damage or myocardial infarction [10] . Mb is a rapid indicator of muscle damage, appearing in the urine 30 min after exertion or injury [11] , and can remain increased in circulation for up to five days post-injury [12] . Although sample collection is very simple, improper sample preparation can cause inaccurate results of Mb concentration. Mb deteriorates rapidly in urine, and its stability can be affected by the pH and temperature of the sample [10] .
• Be increased in a manner that directly correlates with the degree of injury; • Would have a consistent temporal pattern of expression in response to injury; • Be detected in a blood or other accessible body fluid-based assay system. Novel biomarkers to consider? Novel biochemical markers, such as the candidates identified below, are receiving attention for their high sensitivity and/or temporal clarity. We acknowledge that as large-scale proteomics ana-lysis becomes more commonplace, the number of biomarker candidates will expand considerably. Xin
What are the ideal attributes of a muscle damage biomarker? An ideal biomarker of skeletal muscle damage would demonstrate the following characteristics:
Xin, a cytoskeletal adapter protein, was recently identified as a novel biomarker of skeletal muscle damage [14] . Although undetectable within the belly of uninjured skeletal muscle, Xin expression increases with damage severity in a highly correlated manner (regardless whether the damage is a result of myopathy or eccentric exercise in healthy individuals). What’s more, it has been found that Xin expression following acute injury consistently peaked at 12 h postinjury at the mRNA level [15] , and 24 h postinjury at the protein level [16] . While many of the biomarkers noted are found in both cardiac and skeletal muscle (striated), Xin isoforms are differentially expressed (isoform A is predominant in cardiac and isoform B in skeletal muscle) allowing for distinction between damage in these two tissues. If Xin is indeed an ideal biomarker, future work will elucidate the expression profile of Xin within the serum, and determine whether the tight temporal and damage-severity expression patterns still exist.
• Be an exclusive product of skeletal muscle;
Troponin
• Be expressed at minimal levels in an undamaged sample. This feature is of vital importance as baseline readings of muscle damage markers (i.e., measures taken when muscle is healthy and undamaged) are often unknown. A diagnostic tool where a measurable increase in biomarker content is consistent with muscle damage will allow any clinician/researcher to note damage without knowing the baseline biomarker values of the affected individual;
Serum troponin levels have been used for assessment of cardiomyocyte injury and skeletal muscle damage for a number of years [3] . Like Xin, troponin has tissue-specific isoforms allowing distinction between cardiac and skeletal muscle damage (a feature critical if one were interested in identifying cardiomyocyte damage in persons with myopathy). What may make skeletal muscle troponin (sTnI) an interesting biomarker to pursue is that sTnI exists in two isoforms, slow (ssTnI) and fast (fsTnI), corresponding to slowand fast-twitch muscles, respectively. As a general
Lactate dehydrogenase
LDH is an enzyme responsible for the reversible conversion of pyruvate to lactate. LDH is extruded into the circulation from cells as a result of muscle damage, but like other biomarkers, has a notable degree of interperson variability [3] and the detection levels are much lower than that of serum CK [13] . Though CK, myoglobin and LDH levels can be measured without invasive techniques such as a muscle biopsy, a number of factors contribute to their variability in circulating levels at rest, and in their expression postdamage, limiting the viability of their results.
376
• Be increased in a consistent manner, regardless of the type of muscle damage (trauma vs myopathy for example);
Biomarkers Med. (2014) 8(3)
future science group
Potential biomarkers of skeletal muscle damage
damage biomarker, the use of sTnI is hampered by the disparity [17] ; however, this dichotomy may prove useful if one were to investigate disease or injury states that specifically target fast- or slow-twitch muscle fibers [17–19] . miRNAs
The recent emergence of miRNAs has garnered significant attention in both the world of basic science, and the area of muscle damage biomarkers. These endogenous, small noncoding RNAs may prove useful as muscle damage biomarkers due to their size, tissue-specificity and relative abundance and stability in the plasma. Of particular interest is the work of Laterza and colleagues [20] , who demonstrated that plasma miR133a levels served as a very sensitive diagnostic measure for detecting damage induced by skeletal muscle toxicants. The authors noted that the sensitivity of plasma miR133a was much greater than that of CK, which was only slightly elevated in one rodent following this type of injury. Furthermore, plasma miR133a levels were not elevated when liver was damaged by toxin injection, indicating tissue specificity [20] . References 1
Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J. Appl. Physiol. 91(2), 534–551 (2001).
2
Mense S. The pathogenesis of muscle pain. Curr. Pain Headache Rep. 7(6), 419–425 (2003).
3
Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage. Clin. Chem. Lab. Med. 48(6), 757–767 (2010).
4
Pearce JM, Pennington RJ. Walton JN. Serum enzyme studies in muscle disease. II. Serum creatine kinase activity in muscular dystrophy and in other myopathic and neuropathic disorders. J. Neurol. Neurosurg. Psychiatry 27(3), 96–99 (1964).
5
6
7
8
Swaiman K, Sandler B. The use of serum creatine phosphokinase and other serum enzymes in the diagnosis of progressive muscular dystrophy. J. Pediatr. 63(6), 1116–1119 (1963). Amelink GJ, Koot RW, Erich WB, Van Gijn J, Bär PR. Sexlinked variation in creatine kinase release, and its dependence on oestradiol, can be demonstrated in an in-vitro rat skeletal muscle preparation. Acta Physiologica Scandinavica 138(2), 115–124 (1990). Wong ET, Cobb C, Umehara MK et al. Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. Am. J. Clin. Pathol. 79(5), 582–586 (1983). Spargo E. The acute effects of alcohol on plasma creatine kinase (CK) activity in the rat. J. Neurol. Sci. 63(3), 307–316 (1984).
future science group
Editorial
Future studies will help to elucidate whether miRNA expression is a direct or indirect consequence of muscle damage. Additionally, future studies are needed to determine whether expression following various forms of muscle damage follows a specific temporal pattern. Skeletal muscle damage biomarkers are critical tools for healthcare professionals and researchers alike. Whether it be in clinical trials, research studies or exercise therapy prescriptions, the use of these biomarkers will present a sensitive and reliable index of the degree of muscle injury so the best next steps may be made. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. 9
Dale KM, White CM, Henyan NN, Kluger J, Coleman CI. Impact of statin dosing intensity on transaminase and creatine kinase. Am. J. Med. 120(8), 706–712 (2007).
10
Chen-Levy Z, Wener MH, Toivola B, Daum P, Reyes M, Fine JS. Factors affecting urinary myoglobin stability in vitro. Am. J. Clin. Pathol. 123(3), 432–438 (2005).
11
Ascensao A, Rebelo A, Oliveira E, Marques F, Pereira L, Magalhaes J. Biochemical impact of a soccer match – analysis of oxidative stress and muscle damage markers throughout recovery. Clin. Biochem. 41(10), 841–851 (2008).
12
Neubauer O, König D, Wagner KH. Recovery after an Ironman triathlon: sustained inflammatory responses and muscular stress. Eur. J. Appl. Physiol. 104(3), 417–426 (2008).
13
Bessa A, Oliveira VN, De Agostini GG et al. Exercise intensity and recovery: Biomarkers of injury, inflammation and oxidative stress. J. Strength Cond. Res. doi:10.1519/ JSC.0b013e31828f1ee9 (2013) (Epub ahead of print).
14
Nilsson MI, Nissar AA, Al-Sajee D et al. Xin is a marker of skeletal muscle damage severity in myopathies. Am. J. Pathol. 183(6), 1703–1709 (2013).
15
Hawke TJ, Atkinson DJ, Kanatous SB, Van der Ven PFM, Goetsch SC, Garry DJ. Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 293(5), C1636–C1644 (2007).
16
Nissar AA, Zemanek B, Labatia R et al. Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation? Am. J. Physiol. Cell Physiol. 302(1), C220–C227 (2012).
17
Chapman DW, Simpson JA, Iscoe S, Robins T, Nosaka K. Changes in serum fast and slow skeletal troponin I
www.futuremedicine.com
377
Editorial Rebalka & Hawke concentration following maximal eccentric contractions. J. Sci. Med. Sport 16(1), 82–85 (2013). 18
378
Gehrig SM, Koopman R, Naim T, Tjoakarfa C, Lynch GS. Making fast-twitch dystrophic muscles bigger protects them from contraction injury and attenuates the dystrophic pathology. Am. J. Pathol. 176(1), 29–33 (2010).
Biomarkers Med. (2014) 8(3)
19
Vijayan K, Thompson JL, Riley DA. Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles. J. Appl. Physiol. 85(3), 1017–1023 (1998).
20
Laterza OF, Lim L, Garrett-Engele PW, Vlasakova K, Muniappa N, Tanaka WK. Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin. Chem. 55(11), 1977–1983 (2009).
future science group
