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Molecular and Cellular Mechanisms of Angiogenesis

Protease-activated receptors, cyclo-oxygenases and pro-angiogenic signalling in endothelial cells

Caroline P.D. Wheeler-Jones, Charlotte Farrar, Elena Garonna
Biochemical Society Transactions Dec 01, 2009, 37 (6) 1179-1183; DOI: 10.1042/BST0371179
Caroline P.D. Wheeler-Jones
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
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  • For correspondence: cwheeler@rvc.ac.uk
Charlotte Farrar
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
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Elena Garonna
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
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Abstract

COX (cyclo-oxygenase)-2 and members of the PAR (protease-activated receptor) family (PARs 1–4) are highly overexpressed in a number of angiogenesis-dependent pathologies, including advanced atherosclerosis and cancer. An appreciation of the potential role(s) of PARs and COX enzymes in physiological angiogenesis is, however, currently lacking. Exposure of human endothelial cells to serine proteases (e.g. thrombin) or to PAR-selective agonist peptides leads to a wide range of cellular responses, including enhanced expression of COX-2, and we have shown that this induction depends on activation of classic pro-inflammatory signalling elements [e.g. MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor κB)]. Our current studies suggest that COX-2-derived mediators are important autocrine regulators of PAR-stimulated angiogenesis. This mechanism could help us to explain how this novel family of receptors couple vascular inflammation with repair and angiogenesis in health and disease.

  • angiogenesis
  • arachidonic acid
  • cyclo-oxygenase (COX)
  • endothelial cell
  • prostanoid
  • protease-activated receptor (PAR)

Footnotes

  • Molecular and Cellular Mechanisms of Angiogenesis: Biochemical Society Focused Meeting held at University of Chester, Chester, U.K., 15–17 July 2009. Organized and Edited by Ian Zachary (University College London, U.K.) and Sreenivasan Ponnambalam (Leeds, U.K.).

Abbreviations: AA, arachidonic acid; COX, cyclo-oxygenase; GPCR, G-protein-coupled receptor; HUVEC, human umbilical-vein endothelial cell; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; PAR, protease-activated receptor; PG, prostaglandin; PGIS, prostacyclin synthase; PLA2, phospholipase A2; PI3K, phosphoinositide 3-kinase; TxA2, thromboxane A2; VEGF, vascular endothelial growth factor

  • © The Authors Journal compilation © 2009 Biochemical Society
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December 2009

Volume: 37 Issue: 6

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Protease-activated receptors, cyclo-oxygenases and pro-angiogenic signalling in endothelial cells
Caroline P.D. Wheeler-Jones, Charlotte Farrar, Elena Garonna
Biochemical Society Transactions Dec 2009, 37 (6) 1179-1183; DOI: 10.1042/BST0371179
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Protease-activated receptors, cyclo-oxygenases and pro-angiogenic signalling in endothelial cells
Caroline P.D. Wheeler-Jones, Charlotte Farrar, Elena Garonna
Biochemical Society Transactions Dec 2009, 37 (6) 1179-1183; DOI: 10.1042/BST0371179

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  • Article
    • Abstract
    • COXs (cyclo-oxygenases) and endothelial cell function
    • PARs and endothelial cell prostanoid synthesis
    • PAR-mediated regulation of angiogenesis: a role for COXs?
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Keywords

angiogenesis
arachidonic acid
cyclo-oxygenase (COX)
endothelial cell
prostanoid
protease-activated receptor (PAR)

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