Biomedical Engineering Reference
In-Depth Information
aging process occurs in COPD patients with an SMD has not been explored
before, but we are currently investigating this possibility (78).
F. Nitric Oxide
Nitric oxide (NO) is a free radical molecule synthesized from the amino acid
l-arginine by the action of three NO synthases (NOS) (79), all of which are
expressed in human muscle (80). Two NOS isoforms—the so-called type I,
neuronal NOS (nNOS) or brain NOS (bNOS) and type III or endothelial
NOS (eNOS)—are expressed constitutively, while the third isoform—type
II or inducible NOS (iNOS)—is expressed in response to a variety of stimuli,
including cytokines, oxidants, and
=
or hypoxia (80). The role of NO in the
pathogenesis of an SMD in COPD is unclear. Yet, systemic inflammation
can upregulate the expression of iNOS in skeletal muscle (81). Preliminary
results from our laboratory suggest that this actually occurs in COPD
patients who loose weight (82). In turn, the increased NO production result-
ing from iNOS up-regulation can cause protein nitrotyrosination and facil-
itate protein degradation through the U
=
P system (63), and
=
or enhance
skeletal muscle apoptosis (83). Results from our laboratory indicate that
both do indeed occur in patients with COPD and low body weight
(67,82). Finally, iNOS induction can also cause contractile failure (84), thus
potentially limiting exercise tolerance in these patients.
G. Tobacco Smoke
Tobacco smoke is the main risk factor for COPD (85). Tobacco smoke
reaches the systemic circulation, as shown by the increased prevalence of
coronary artery disease and endothelial dysfunction in smokers (21,22)
and contains many substances potentially harmful for the skeletal muscle.
For instance, nicotine alters the expression of important growth factors,
such as TGF-
b
1, involved in the maintenance of the muscular mass (86)
and competes with acetylcholine for its receptor at the neuromuscuolar
junction, thus having the potential to affect directly muscle contraction
(87). Therefore, it is possible that tobacco smoke by itself may also contri-
bute to an SMD in COPD.
H. Genetic Susceptibility
Not all smokers develop COPD (85). Likewise, not all COPD patients lose
muscle mass during the course of their disease (24). Although this may be
related to the severity (24) or phenotype of the disease (88), a genetic com-
ponent similar to that suggested explaining the development of COPD in
only a fraction of smokers (89,90) cannot be excluded. The potential genes
involved in this process are unknown. Some potential candidate genes
include the angiotensin-converting enzyme (ACE) gene, those of several
