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5.9 Effects of Extracellular Nucleotides on Angiogenic Responses
in Endothelial Cells
Although extracellular nucleotide-mediated signaling has been implicated in various
physiological and pathologic conditions, there is limited information regarding the
role of extracellular nucleotides in modulating endothelial cell proliferation. It has
been postulated that endothelial cells from various vascular beds exhibit tremendous
functional and morphological heterogeneity [5]. In particular, endothelial cells of
large blood vessels such as pulmonary artery and aorta possess phenotypical char-
acteristics different from those of endothelial cells of microvascular beds. In this
regard, it was expected that the proliferative and angiogenic capacities of endothe-
lial cells of large vessels and microvessels should also differ. To test this hypothesis,
we measured the rate of DNA synthesis in endothelial cells isolated from aorta
(AOEC), main pulmonary artery (MPAEC), lung microvessels (MVEC) and PA
adventitial vasa vasorum (VVEC) (Fig. 5.3). It was found that extracellular ATP
at concentrations of 10
−
6
10
−
3
M, stimulated dramatic increases in DNA synthe-
sis in VVEC and DPAEC (up to 12-fold), but has very little effect on AOEC and
−
Fig. 5.3
Extracellular ATP exerts different proliferative responses in microvascular and macrovas-
cular endothelial cells. Growth arrested (72 h, serum-free DMEM) vasa vasorum endothelial cells
(VVEC), aorta endothelial cells (AOEC), main pulmonary artery endothelial cells (MPAEC) and
lung microvascular endothelial cells (MVEC) were stimulated with extracellular ATP from 10
−
9
to 10
−
3
M in the presence of 0.125
Ci [
3
H]-thymidine for 24 h, and incorporated radioactivity
was determined in total cell lysates. The results are expressed as means
μ
±
S.E; (
n
=
3). Shown are
the data representative for each endothelial cell type
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