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 74

Ta ble 5.1 Phenotypical characteristics of pulmonary artery adventitial VVEC

CD31/PECAM +++

vWf +

Flt-1 +

Flk-1 ++

eNOS +

Tie-2 ++

Tie-1 +

Ephrin B2 +

CD133 ++

CD34 +

c-kit +

binding of lectin Lycopersicon esculentum +++

uptake of acetylated low density lipoproteins (Dil-Ac-LDL) +++

Data were obtained by immunofluorescence analysis: +++ indicates very
high expression level; ++ indicates high expression level; + indicates
variable expression level

In addition, VVEC express Flt-1, Tie-2, Ephrin B2, CD133 and c-kit. Our data also
demonstrate the ability of VVEC to bind the lectin Licopercsicon Esculentum ; and
uptake acetylated low density lipoproteins labeled with 1,1 -dioctadecyl-3,3,3 ,3 -
tetramethylindo-carbocyanine perchlorate (DiI-Ac-LDL) (Table 5.1). Our data also
demonstrates the ability of VVEC to form interconnecting networks on poly-
merized Matrigel and in co-cultures with adventitial fibroblasts suggesting an
angiogenic capability of VVEC in vitro. Therefore, the cultured adventitial VVEC
can be used as a physiologically relevant model cell system to study endothelial
angiogenesis.

5.5 Extracellular Nucleotides as Important Regulators
of Vascular Functions

Endogenous autocrine and paracrine soluble factors, released under hypoxic condi-
tions from the cells of vasculature and blood circulation are important contributors
to angiogenesis [27, 32, 50, 52, 74]. An autocrine mechanism for the regulation
of vascular cell growth has been demonstrated for several vasoactive compounds,
including TGF- , VEGF, prostaglandin E2, and adrenomedulin [41, 44, 54, 93].

However, quite often the efforts to prevent pathologic angiogenesis and vascu-
lar remodeling by using tyrosine kinase or cytokine receptor antagonists have
not resulted in a intended clinical outcome, suggesting that additional signaling
mechanisms may contribute to the angiogenic process.
Extracellular purines and pyrimidines (ATP, ADP, AMP, adenosine, UTP and
UDP) have been proposed as important regulators of vascular cell proliferation,
migration, chemotaxis and secretory responses [2-4, 11, 19, 23, 24, 28, 72, 73, 83].
The effects of extracellular nucleotides are mediated through P2Y (metabotropic),

β