Role of Purine-Converting Ecto-Enzymes in Angiogenic Phenotype of Pulmonary Artery Adventitial Vasa Vasorum Endothelial Cells of Chronically Hypoxic Calves - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 72

Fig. 5.1 Hypoxia induces vasa vasorum neovascularization in the PA adventitia of chronically
hypoxic calves. H&E staining of lung sections of control and hypoxic and calves demonstrates
that thickening of the pulmonary artery vessel wall is associated with an apparent increase in the
density of vasa vasorum ( red arrows ) in vessels from hypoxic animals ( b ), compared with vessels
from normoxic animals ( a ). Scale bar represents 100 μ M; (AW = airways; PA = pulmonary

artery)

excessively proliferating lung microvascular endothelial cells obliterate the vas-
cular lumen and contribute to the disruption of the pulmonary blood flow [16].
Vasa vasorum endothelial cells observed in the adventitia of the large pulmonary
arteries (PA) are though to be derived from bronchial circulation. Expansion of the
bronchial vessels in the ischemic lung parenchyma and the pulmonary arteries has
been demonstrated in patients with chronic thromboembolic disease that suggests
a unique proliferative and invasive capacity of endothelial cells of the these sys-
temic vessels [61]. Together, these observations imply that angiogenic vasa vasorum
expansion may be a common feature of specific pulmonary and systemic vascular
diseases and that hypoxic microenvironment may facilitate the angiogenic process
[17, 26, 58, 60, 64].

5.3 Hypoxia-Induced Vasa Vasorum Neovascularization
Represents an Angiogenesis of Systemic Vessels
in the Pulmonary Circulation

In fact, the observed pulmonary artery adventitial thickening supported by an
increased systemic blood flow (vasa vasorum), represents a unique angiogenesis
model system. This involves a direct interaction between cells of pulmonary and
systemic blood vessels, explicitly, angiogenesis of the systemic (bronchial) micro-
circulation in the pulmonary artery vascular wall. Moreover, we have demonstrated
the recruitment of circulating progenitor and inflammatory cells to the PA adventitia
of chronically hypoxic calves, suggesting that the expanding vasa vasorum appears
to function as a port and conduit for entry and delivery of circulating inflammatory
cells in the vessel wall [78]. Therefore, in many aspects hypoxia-induced adventi-
tial inflammation and vasa vasorum neovascularization observed in neonatal calves,