Biomedical Engineering Reference
In-Depth Information
the origin of both systemic and pulmonary hypertensive disorders. In pri-
mary (or idiopathic) pulmonary hypertension (PPH), proliferation of
endothelial cells is prominent and causes enlargement of the arterial wall
and narrowing and obliteration of the vessel lumen (16). Lee et al. (17) eval-
uated the clonal nature of endothelial cells proliferating in the plexiform
lesions of patients with pulmonary arterial hypertension by using the human
androgen receptor gene assay. They showed that in plexiform lesions of
PPH endothelial cell proliferation was essentially monoclonal, whereas in
the associated forms of pulmonary arterial hypertension (congenital heart
defects, scleroderma) it was polyclonal (17). These findings suggest that a
somatic genetic alteration similar to that present in neoplastic disorders
might be responsible for endothelial cell proliferation in PPH. By contrast,
in ''secondary'' pulmonary hypertension, the polyclonal nature of endothe-
lial cell proliferation seems to be the result of a reaction in response to a
variety of stimulus (shear stress, inflammation).
Contrasting with severe forms of pulmonary arterial hypertension,
endothelial cell proliferation is not a characteristic feature of pulmonary
vascular remodeling in COPD. Santos et al. (18) characterized the cells pre-
sent in hyperplasic intimas of pulmonary muscular arteries in COPD. By
using a monoclonal antibody against Factor VIII, they showed that in
COPD endothelial cells outline the innermost portion of pulmonary muscu-
lar arteries in a single cell layer (18). No proliferation of endothelial cells was
detected within the intimal layer, thereby excluding endothelial cell prolif-
eration as the cause of intimal enlargement, at variance with what occurs
in PPH.
B.
Endothelial Dysfunction
The absence of endothelial cell proliferation does not exclude alterations in
endothelial function. Indeed, endothelial dysfunction in pulmonary arteries
has been shown at different degrees of COPD severity (6,19). In pulmonary
arteries of explanted lungs from patients with end-stage COPD who under-
went lung transplantation, Dinh-Xuan et al. (19) showed a significant reduc-
tion of endothelium-dependent vasodilation induced by acetylcholine, when
compared with control subjects. In a similar study conducted in pulmonary
arteries from lung specimens of patients with mild-to-moderate COPD, the
authors also showed reduction of endothelium-dependent vasorelaxation
induced by both acetylcholine and ADP, when compared with nonsmokers
(6). These studies denote that endothelial dysfunction of pulmonary arteries
is a common feature of COPD and that it is present not only in advanced
disease, when pulmonary hypertension is usually identified, but also in
patients with mild disease, when pulmonary vascular involvement is not
clinically apparent.
