CD39 and endothelial cells
Endothelial cells and related vascular smooth muscle cells express CD39, which plays a key role in inflammation and thrombus reduction[93]. CD39 expressed by vascular endothelial cells could limit excessive polymorphonuclear leukocyte infiltration by providing increased ADO concentrations at hypoxic and inflammation sites[60]. The arterial expression and functionality of CD39 is decreased in hypertension. The reduced ectonucleotidase activity of CD39 may enhance pathology-associated vascular damage, increase endothelial permeability and inflammation, and increase the risk of end-organ damage and thrombogenesis [94]. In tumor environment, the expression of CD39 in vascular system, especially endothelial cells, can promote tumor growth by scavenging eATP[95]. The endothelial CD39/CD73 axis regulates hemostasis by transforming the local environment from a prethrombotic state rich in ATP and ADP into an antithrombotic environment rich in ADO[96-98]. CD39 plays the role of an endothelial thromboregulator by demonstrating that CD39-transfected COS cells acquire the ability to inhibit ADP-induced aggregation in platelet-rich plasma [99-101]. Next to inhibition of platelet activation, the local release of CD39 mRNA in atherosclerotic blood vessels supports the integrity of the endothelium and inhibits extracellular nucleotide-induced smooth muscle cell proliferation[102]. Paradoxically, Aho et al. showed that elevated eATP or inhibition of CD39 activity has a protective effect against DNA damage in endothelial cells [103]. However, this effect could not be replicated in cancer cells.