Biomedical Engineering Reference
In-Depth Information
COPD (15,62). The potential role of inflammation in the pathogenesis of
pulmonary vascular abnormalities associated with COPD has not been
established yet.
Inflammatory cells are a source of cytokines and growth factors that
may target the endothelial cells and contribute to the development of struc-
tural and functional abnormalities of the vessel wall (124). Different
inflammatory mediators, namely prostaglandin E
2
, interleukin (IL) -6,
and IL-1 are capable to induce VEGF mRNA and protein expression
(125,126). In addition, macrophages and T-lymphocytes express VEGF
receptors (127) and VEGF induces monocyte activation and migration
(128,129). Accordingly, it might be speculated that increased VEGF activ-
ity shown in pulmonary arteries at early stages of COPD (13) could be
related, to some extent, with an underlying inflammatory process. This
suggestion is consistent with the fact that the number of inflammatory
cells infiltrating the wall of pulmonary arteries is inversely related to
the endothelial function and directly related to the enlargement of the
intimal layer (62).
D. Cigarette Smoking
Studies performed by the authors have shown prominent changes in
pulmonary arteries of smokers with normal lung function, namely SMC
proliferation (6,18), impairment of endothelial function (6), reduced expres-
sion of eNOS (130), increased expression of VEGF (13), and CD8
รพ
T-cell
infiltrate (62). In general, these changes are indistinguishable from those
seen in pulmonary arteries of COPD patients, and clearly differ from non-
smokers. These observations strongly suggest that cigarette smoke products
might exert a direct effect on vessel structure and function. Studies per-
formed in the 1960s already pointed out this association (131), and Hale
et al. (8) demonstrated structural abnormalities in pulmonary muscular
arteries of smokers, as compared with nonsmokers.
Some of these observations have been replicated in a guinea pig model
chronically exposed to cigarette smoke by Wright and Churg (132). In that
model, exposure to cigarette smoke induces muscularization of precapillary
vessels and increase of pulmonary artery pressure (133) (Fig. 3). Interest-
ingly, these vascular abnormalities are detectable after 2 months of cigarette
smoke exposure only, when there is no evidence of emphysema (133),
thereby implicating that cigarette smoke-induced vascular abnormalities
may antecede the development of pulmonary emphysema (134). Further-
more, using this model, it has been shown that cigarette smoke exposure
induces rapid changes in gene expression of VEGF, VEGF receptor-1,
ET-1, and inducible NOS (135), mediators that control vascular cell growth
and vessel contraction, and that are likely involved in the pathogenesis of
pulmonary vascular changes of COPD.
