Soluble guanylyl cyclase activation promotes angiogenesis

Anastasia Pyriochou, Dimitris Beis, Vasiliki Koika, Christos Potytarchou, Evangelia Papadimitriou, Zongmin Zhou, Andreas Papapetropoulos

Research output: Contribution to journalArticle

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Abstract

Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme carrying a heme prosthetic group that functions as a nitric oxide (NO) sensor. sGC is present in most cells types, including the vascular endothelium, where its biological functions remain largely unexplored. Herein, we have investigated the role of sGC in angiogenesis and angiogenesis-related properties of endothelial cells (EC). Initially, we determined that sGC was present and enzymatically active in the chicken chorioallantoic membrane (CAM) during the days of maximal angiogenesis. In the CAM, inhibition of endogenous sGC inhibited neovascularization, whereas activation promoted neovessel formation. Using zebrafish as a model for vascular development, we did not detect any effect on vasculogenesis upon sGC blockade, but we did observe an abnormal angiogenic response involving the cranial and intersegmental vessels, as well as the posterior cardinal vein. In vitro, pharmacological activation of sGC or adenovirus-mediated sGC gene transfer promoted EC proliferation and migration, whereas sGC inhibition blocked tube-like network formation. In addition, sGC inhibition blocked the migratory response to vascular EC growth factor. Cells infected with sGC-expressing adenoviruses exhibited increased extracellular signal-regulated kinase 1/2 and p38 MAPK activation that was sensitive to sGC inhibition by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, suggesting that these mitogen-activated protein kinases are downstream effectors of sGC in EC. A functional role for p38 in cGMP-stimulated migration was demonstrated using SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H- imidazole]; pharmacological inhibition of p38 attenuated BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl] -pyrimidin-4-ylamine] and sGC overexpression-induced EC mobilization. We conclude that sGC activation promotes the expression of angiogenesis-related properties by EC and that sGC might represent a novel target to modulate neovessel formation.

Original languageEnglish (US)
Pages (from-to)663-671
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume319
Issue number2
DOIs
StatePublished - Nov 24 2006
Externally publishedYes

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Endothelial Cells
Chorioallantoic Membrane
Soluble Guanylyl Cyclase
Adenoviridae
Pharmacology
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Vascular Endothelium
p38 Mitogen-Activated Protein Kinases
Zebrafish
Mitogen-Activated Protein Kinases
Heme
Vascular Endothelial Growth Factor A
Cell Movement
Blood Vessels
Chickens
Veins
Nitric Oxide
Cell Proliferation
Enzymes

ASJC Scopus subject areas

  • Pharmacology

Cite this

Soluble guanylyl cyclase activation promotes angiogenesis. / Pyriochou, Anastasia; Beis, Dimitris; Koika, Vasiliki; Potytarchou, Christos; Papadimitriou, Evangelia; Zhou, Zongmin; Papapetropoulos, Andreas.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 319, No. 2, 24.11.2006, p. 663-671.

Research output: Contribution to journalArticle

Pyriochou, A, Beis, D, Koika, V, Potytarchou, C, Papadimitriou, E, Zhou, Z & Papapetropoulos, A 2006, 'Soluble guanylyl cyclase activation promotes angiogenesis', Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 2, pp. 663-671. https://doi.org/10.1124/jpet.106.108878
Pyriochou A, Beis D, Koika V, Potytarchou C, Papadimitriou E, Zhou Z et al. Soluble guanylyl cyclase activation promotes angiogenesis. Journal of Pharmacology and Experimental Therapeutics. 2006 Nov 24;319(2):663-671. https://doi.org/10.1124/jpet.106.108878
Pyriochou, Anastasia ; Beis, Dimitris ; Koika, Vasiliki ; Potytarchou, Christos ; Papadimitriou, Evangelia ; Zhou, Zongmin ; Papapetropoulos, Andreas. / Soluble guanylyl cyclase activation promotes angiogenesis. In: Journal of Pharmacology and Experimental Therapeutics. 2006 ; Vol. 319, No. 2. pp. 663-671.
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AU - Zhou, Zongmin

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