Cardiac troponin T composition in normal and regenerating human skeletal muscle

Abstract

Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100% cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease

“…probably reflecting foetal gene re-expression of troponin T in damaged muscles, as proposed in other forms of myopathy. 22,23 Ergoreflex sensitivity was significantly higher in patients with subclinical cardiac involvement. This result outlines a potential novel pathogenetic factor that, activated at the level of diseased skeletal muscle, may promote sympathetic activation, possibly contributing to cardiac damage.…”

Novel Recessive TNNT1 Congenital Core‐Rod Myopathy in French Canadians

“…34 The cardiac isoform of troponin T (TnTc) is found at low levels in normal adult skeletal type I myofibers, consistent with its homology with TnTs. 19,35,36 Missense variants in the alpha-helical tropomyosin-binding domain of TnTc decrease its binding affinity for tropomyosin while rendering the thin filament complex hypersensitized to calcium. 37,38 The hypersensitized state arises as a consequence of a slower rate of calcium dissociation from the mutated troponin complex.…”

Towards appreciating appropriate clinical responses to highly sensitive cardiac troponin assays

“…10 Nevertheless, several reports and case studies have documented false-positive cTnT results in patients suffering from primary skeletal muscle diseases, such as polymyositis and Duchenne muscular dystrophy. 11,12 Chronic skeletal disorders are thought to be associated with skeletal muscle expression of cTn and therefore an apparent cross-reactivity of these cTn assays with skeletal troponin. However, it is hard to rule out additional cardiac-derived cTn in these patients when many of them have high risk of cardiac disease.…”