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 85

such as chronic hypoxia and inflammation can modulate extracellular nucleotide
concentrations in the vessel wall through regulating the activity and expression
levels of purine-converting ecto-enzymes, thereby providing their integration into
purinergic signalling networks [21, 67, 68]. In view of the recent data on the
important role of purinergic signaling in endothelial responses under various patho-
logic conditions, it remains necessary to explore the extent chronic and acute
hypoxia might affect the extracellular nucleotide metabolism. Since exogenous ATP
and ADP contribute to angiogenic activation of VVEC, the above peculiarities in
endothelial nucleotide metabolism could be especially relevant to hypoxia-induced
angiogenic expansion of the PA adventitial vasa vasorum and possibly microvas-
cular networks in different tissues. Keeping in mind endothelial phenotypical and
functional heterogeneity, a role of individual purine-converting ecto-enzymes in
the regulation of extracellular nucleotide profile should be precisely evaluated
in cellular and animal model systems allowing genetic alteration in the expres-
sion of purine-converting ecto-enzymes. Another fascinating question remains
as to whether regulation of the expression and the activity of purine-converting
enzymes under various pathological conditions occur in a coordinated manner,
or they can be regulated independently in a cell-type and stimulus-dependent
manner.
Acknowledgments This work was supported by National Heart, Lung, and Blood Institute
Program Project Grant HL14985 (to K.R.S), the Finnish Academy of Sciences and the Sigrid
Juselius Foundation (to G.Y.) National Heart, Lung, and Blood Institute R01 grant HL 086783 (to
E.V.G.) and an American Heart Association grant 0665464Z (to E.V.G.). We also wish to thank
Mr. Philip Weston for editorial help.
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