Cell Surface ATP Synthase: A Potential Target for Anti-Angiogenic Therapy - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function - page 152

and downstream cascade(s) activated by ATP also remain to be determined. Given
that ATP has been demonstrated to be pro-angiogenic for pulmonary vasa vasorum
endothelial cells but not other endothelial cell types, ATP synthase could also play
different roles in different vascular beds [18]. The degree to which ATP synthase
contributes to endothelial cell responses to shear stress and ATP release also contin-
ues to be debated in the literature [19, 52]. Furthermore, the manner in which flow
activates cell surface ATP synthase activity is not understood. Finally, the down-
stream signaling induced by binding of the ligands CF6 and EMAP II to endothelial
cell ATP synthase have yet to be elucidated. Thus, a great deal of further research
is required to achieve a fuller understanding of the roles played by cell surface ATP
synthase in endothelial cell functioning.
References
1. Ando J, Ohtsuka A, Korenaga R, Kamiya A. (1991) Effect of extracellular ATP level on flow-
induced Ca ++ response in cultured vascular endothelial cells. Biochem Biophys Res Commun
179(3):1192-9.
2. Arakaki N, Nagao T, Niki R, Toyofuku A, Tanaka H, Kuramoto Y, Emoto Y, Shibata H,
Magota K, Higuti T. (2003) Possible role of cell surface H + -ATP synthase in the extracellular
ATP synthesis and proliferation of human umbilical vein endothelial cells. Mol Cancer Res
1(13):931-9.
3. Awasthi N, Schwarz MA, Verma V, Cappiello C, Schwarz RE. (2009) Endothelial monocyte
activating polypeptide II interferes with VEGF-induced proangiogenic signaling. Lab Invest
89(1):38-46.
4. Beerepoot LV, Witteveen EO, Groenewegen G, Fogler WE, SimBK, Sidor C, Zonnenberg BA,
Schramel F, Gebbink MF, Voest EE. (2003) Recombinant human angiostatin by twice-daily
subcutaneous injection in advanced cancer: a pharmacokinetic and long-term safety study.
Clin Cancer Res 9(11):4025-33.
5. Berger AC, Alexander HR, Tang G, Wu PS, Hewitt SM, Turner E, Kruger E, Figg WD,
Grove A, Kohn E, Stern D, Libutti SK. (2000) Endothelial monocyte activating polypep-
tide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis. Microvasc Res
60(1):70-80.
6. Bodin P, Bailey D, Burnstock G. (1991) Increased flow-induced ATP release from iso-
lated vascular endothelial cells but not smooth muscle cells. Br J Pharmacol 103(1):
1203-5.
7. Bodin P, Burnstock G. (2001) Evidence that release of adenosine triphosphate from endothe-
lial cells during increased shear stress is vesicular. J Cardiovasc Pharmacol 38(6):900-8.
8. Boyer PD. (1997) The ATP synthase-a splendid molecular machine. Annu Rev Biochem
66:717-49.
9. Boyer PD. (2000) Catalytic site forms and controls in ATP synthase catalysis. Biochim
Biophys Acta 1458(2-3):252-62.
10. Capaldi RA, Aggeler R. (2002) Mechanism of the F(1)F(0)-type ATP synthase, a biological
rotary motor. Trends Biochem Sci 27(3):154-60.
11. Chang SY, Ko HJ, Heo TH, Kang CY. (2005) Heparan sulfate regulates the antiangio-
genic activity of endothelial monocyte-activating polypeptide-II at acidic pH. Mol Pharmacol
67(5):1534-43.
12. Chang SY, Park SG, Kim S, Kang CY. (2002) Interaction of the C-terminal domain of p43 and
the alpha subunit of ATP synthase. Its functional implication in endothelial cell proliferation.
J Biol Chem 277(10):8388-94.