The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis

Cheikh I. Seye, Gary A. Weisman

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

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 P2Y 2R leading to the up-regulation of VCAM-1. The P2Y2R also contains an arginine-glycine-aspartate domain that mediates interactions with αvβ35 integrins that enable nucleotides to increase cell migration, an important event in inflammation and tumor angiogenesis. Taken together, these findings indicate that P2Y 2Rs can stimulate multiple signaling pathways to promote a variety of pathological responses underlying chronic inflammation, angiogenesis in tumors and atherosclerosis.

Original languageEnglish (US)
Title of host publicationExtracellular ATP and Adenosine as Regulators of Endothelial Cell Function
Subtitle of host publicationImplications for Health and Disease
PublisherSpringer Netherlands
Pages57-72
Number of pages16
ISBN (Print)9789048134342
DOIs
StatePublished - Dec 1 2010

Keywords

  • Adhesion
  • Angiogenesis
  • Artery
  • Atherosclerosis
  • Calcium
  • Endothelial cell
  • G protein
  • Inflammation
  • Microvessels
  • Migration
  • Monocyte
  • Nucleotide
  • P2Y receptor
  • Proliferation
  • Smooth muscle cell
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Seye, C. I., & Weisman, G. A. (2010). The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis. In Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease (pp. 57-72). Springer Netherlands. https://doi.org/10.1007/978-90-481-3435-9_4