Biomedical Engineering Reference
In-Depth Information
Figure 3
Photomicrographs of small arteries from guinea pigs exposed to cigarette
smoke during 6 months (A), and sham-smoked (B). Note the development of a com-
plete and thick muscular layer in arterioles of guinea pigs exposed to cigarette smoke.
It is well known that cigarette smoking is a risk factor for the develop-
ment of vascular disease. Active and passive exposure to tobacco smoke
produces endothelial dysfunction in both coronary and systemic arteries
(136). Exposure of pulmonary artery endothelial cells to cigarette smoke
extract causes an irreversible inhibition of eNOS activity, which is due to
a diminished eNOS protein content and mRNA (137). Cigarette smoke con-
tains a number of products that have the potential to induce endothelial
damage. However, the specific product responsible for the inhibition of
eNOS remains unsettled. In this respect, pretreatment with antioxidants
does not protect eNOS from the inhibitory effect of cigarette smoke extract
(137). Cigarette smoke products can also be potential triggers for VEGF
since nicotine and cotinine, in doses similar to those seen in the plasma of
current smokers, upregulate VEGF expression in endothelial cells (138).
VII. PATHOBIOLOGY OF PULMONARY VASCULAR CHANGES
IN COPD
Several evidences discussed above suggest that the initial event in the natural
history of pulmonary hypertension in COPDmight be the lesion of pulmonary
endothelium by cigarette-smoke products with a subsequent downregulation
of eNOS expression and impairment of endothelial function (Fig. 4). It is also
possible that inflammation products could also play a similar role damaging
pulmonary endothelium. One of the consequences of endothelial dysfunction
is the impairment of the reactivity of pulmonary arteries to hypoxia
(12,114,115), thereby contributing to ventilation-perfusion mismatching and
promoting the development of arterial hypoxemia. Endothelial damage results
in an imbalance among factors that regulate cell growth, thereby favoring
proliferation of SMCs and extracellular matrix deposition. Upregulation
