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Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function pp 57–72Cite as

The P2Y2 Nucleotide Receptor in Vascular Inflammation and Angiogenesis

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Abstract

There is compelling evidence for increased neovascularization of blood vessel walls at sites of intimal hyperplasia in models of arterial stenting, angioplasty, and venous bypass graft failure. We have shown that activation of the P2Y2 nucleotide receptor (P2Y2R) in vascular endothelial cells in vitro induces VCAM-1 (vascular cell adhesion molecule-1) expression and promotes the adherence of monocytes. VEGF, a pleiotropic factor that regulates endothelial cell survival, proliferation, and migration through its interaction with two receptor tyrosine kinases, Flt-1 or VEGF receptor-1 and Flk-1/KDR or VEGF receptor-2 also stimulates the expression of VCAM-1 in endothelial cells. Interestingly, our studies indicate that P2Y2R activation promotes the VEGF-independent activation of Flk-1/KDR via Src binding to Src homology (SH3) binding domains in the C-terminal tail of the P2Y2R leading to the up-regulation of VCAM-1. The P2Y2R also contains an arginine-glycine-aspartate domain that mediates interactions with αvβ3/β5 integrins that enable nucleotides to increase cell migration, an important event in inflammation and tumor angiogenesis. Taken together, these findings indicate that P2Y2Rs can stimulate multiple signaling pathways to promote a variety of pathological responses underlying chronic inflammation, angiogenesis in tumors and atherosclerosis.

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Authors and Affiliations

  1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, MS 332, Indianapolis, 46202, Indiana

    Cheikh I. Seye

  2. Department of Biochemistry, 540E Life Sciences Center, University of Missouri, 1201 Rollins Road, Columbia, MO, 65211–7310, USA

    Gary A. Weisman

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Correspondence to Cheikh I. Seye .

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Editors and Affiliations

  1. Dept. Pediatrics, Pediatric Clinical Services, University of Colorado, Denver, East 19th Avenue 12700, Aurora, 80045, USA

    Evgenia Gerasimovskaya

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline Ave. 99, Boston, 02215, USA

    Elzbieta Kaczmarek

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Seye, C.I., Weisman, G.A. (2010). The P2Y2 Nucleotide Receptor in Vascular Inflammation and Angiogenesis. In: Gerasimovskaya, E., Kaczmarek, E. (eds) Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3435-9_4

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