Myoglobin plasma level related to muscle mass and fiber composition – a clinical marker of muscle wasting?

Abstract

Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p< 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.

Do muscle fiber conduction slowing and decreased levels of circulating muscle proteins represent sensitive markers of steroid myopathy? A pilot study in Cushing's disease

“…This result is in line with the above-mentioned observation of Khaleeli et al (1) as well as with the differences in circulating muscle proteins that were observed by Weber et al (38) while comparing cachectic cancer patients and healthy controls. Interestingly, we found a greater difference between patients and controls in CK than in myoglobin levels: this could reflect the preferential impairment of type 2 fibers, which present high levels of CK expression, whereas myoglobin is preferentially expressed in oxidative type 1 fibers that are less affected by the myopathic process.…”

Cachexia has only one meaning

“…Are the diverse chronic (or not so chronic) cachexia conditions related? The cachexic patients presented by Weber et al [2] all had cancer. Skipworth et al [3] recently reviewed cancer cachexia.…”

“…The fact that creatine kinase and myoglobin were not elevated is of some mechanistic interest, since active muscle destruction would have featured elevation of both myoglobin and creatine kinase. Weber et al [2] performed muscle biopsies on 11 patients and 15 control subjects. A marked size reduction in type 1 and 2 fibers occurred in the cachexic patients that corresponded to the reduction in cross-sectional area and correlated significantly with the reduced myoglobin levels.…”

“…Elucidation of the triggers would appear more promising. The muscle biopsies performed by Weber et al [2] could be helpful in this regard. Possibly, very early changes that could be identified by serial biopsy might be helpful.…”

Mass spectrometric detection of candidate protein biomarkers of cancer cachexia in human urine

“…In particular, the dystrophin glycoprotein complex appears dysregulated and the sarcolemma becomes permeable to vital dyes. However, the severity of membrane damage would appear, at first glance, to be insufficient to cause a free permeation of intracellular proteins, particularly as circulating levels of creatine kinase (CK), a marker of muscle damage, are not elevated (9,10).…”