Biomedical Engineering Reference
In-Depth Information
consequences: (1) it contributes significantly to weight loss (24), a poor prog-
nostic factor in these patients (25,26); and (2) it is a main cause of exercise
limitation (27) having a profound impact on their quality of life (31,32).
Thus, appropriate treatment of an SMD should be a priority in the clinical
management of COPD (27). Currently, this is mostly based upon reha-
bilitation programes, nutritional support and, perhaps, oxygen therapy
(18,30,33-37). However, more specific and effective therapies need to be
developed. Yet, for this purpose, a better understanding of the mechanisms
leading to an SMD in COPD is crucial (38,39) (Fig. 1).
Conceptually, it may be useful to consider that an SMD in COPD is
probably characterized by two different, although possibly related, phenom-
ena: (1) net loss of muscle mass (atrophy), an intrinsic muscular phenom-
enon; and (2) dysfunction or malfunction of the remaining muscle. In
turn, muscle malfunction may be secondary to either intrinsic muscle
alterations—mitochondrial abnormalities, loss of contractile proteins—or
Figure 1
Signal transduction pathways potentially implicated in skeletal muscle
mass loss in patients with COPD: (1) TNF-
a
and IFN-
g
can activate death domains
and NF-
k
B nuclear translocation leading to a marked inhibition of the activity of
several skeletal muscle transcription factors, such as MyoD and MEF2 which are
highly relevant for muscle growth, repair, and differentiation, whereas the cytokine
myostatin can inhibit muscle regeneration via p21 expression; (2) skeletal muscle
proteolysis is enhanced by the over-expression of ubiquitin-proteasome elements
(atrogin-1, MURF); and (3) down-regulation of skeletal muscle growth factors as
IGF-1 prevents skeletal muscle hypertrophy via inhibition of the activation of
calcium-dependent kinases, NF-AT, and histone deacetylases.
