The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis

Cheikh Seye, Gary A. Weisman

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

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
Title of host publicationExtracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease
PublisherSpringer Netherlands
Pages57-72
Number of pages16
ISBN (Print)9789048134342
DOIs
StatePublished - 2010

Fingerprint

Purinergic P2Y2 Receptors
Blood Vessels
Vascular Cell Adhesion Molecule-1
Endothelial cells
Nucleotides
Inflammation
Vascular Endothelial Growth Factor Receptor-2
Endothelial Cells
Chemical activation
Vascular Endothelial Growth Factor A
Cell Movement
Tumors
Tunica Intima
Vascular Endothelial Growth Factor Receptor
src Homology Domains
Blood vessels
Cell proliferation
Receptor Protein-Tyrosine Kinases
Angioplasty
Aspartic Acid

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)

Cite this

Seye, C., & 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

The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis. / Seye, Cheikh; Weisman, Gary A.

Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease. Springer Netherlands, 2010. p. 57-72.

Research output: Chapter in Book/Report/Conference proceedingChapter

Seye, C & Weisman, GA 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. Springer Netherlands, pp. 57-72. https://doi.org/10.1007/978-90-481-3435-9_4
Seye C, Weisman GA. 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. Springer Netherlands. 2010. p. 57-72 https://doi.org/10.1007/978-90-481-3435-9_4
Seye, Cheikh ; Weisman, Gary A. / The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis. Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease. Springer Netherlands, 2010. pp. 57-72
@inbook{892c8636b517498c9ca8bf000cbe2998,
title = "The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis",
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 αvβ3/β5 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.",
keywords = "Adhesion, Angiogenesis, Artery, Atherosclerosis, Calcium, Endothelial cell, G protein, Inflammation, Microvessels, Migration, Monocyte, Nucleotide, P2Y receptor, Proliferation, Smooth muscle cell, Tyrosine kinase",
author = "Cheikh Seye and Weisman, {Gary A.}",
year = "2010",
doi = "10.1007/978-90-481-3435-9_4",
language = "English",
isbn = "9789048134342",
pages = "57--72",
booktitle = "Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease",
publisher = "Springer Netherlands",

}

TY - CHAP

T1 - The P2Y2 nucleotide receptor in vascular inflammation and angiogenesis

AU - Seye, Cheikh

AU - Weisman, Gary A.

PY - 2010

Y1 - 2010

N2 - 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 αvβ3/β5 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.

AB - 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 αvβ3/β5 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.

KW - Adhesion

KW - Angiogenesis

KW - Artery

KW - Atherosclerosis

KW - Calcium

KW - Endothelial cell

KW - G protein

KW - Inflammation

KW - Microvessels

KW - Migration

KW - Monocyte

KW - Nucleotide

KW - P2Y receptor

KW - Proliferation

KW - Smooth muscle cell

KW - Tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=84900041149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900041149&partnerID=8YFLogxK

U2 - 10.1007/978-90-481-3435-9_4

DO - 10.1007/978-90-481-3435-9_4

M3 - Chapter

AN - SCOPUS:84900041149

SN - 9789048134342

SP - 57

EP - 72

BT - Extracellular ATP and Adenosine as Regulators of Endothelial Cell Function: Implications for Health and Disease

PB - Springer Netherlands

ER -