Soluble guanylate cyclase activation promotes angiogenesis

Anastasia Pyriochou, Christos Potytarchou, Evangelia Papadimitriou, Andreas Papapetropoulos

Research output: Contribution to journalArticle

Abstract

Soluble guanylyl cyclase (sGC) is an α/β heterodimeric protein that is activated by nitric oxide (NO), yielding increased intracellular levels of cGMP. Evidence in the literature suggests that endogenously produced NO, as well as NO-donors, stimulate angiogenesis by increasing endothelial cell (EC) proliferation, migration and organization of EC into vascular networks. Moreover, NO mediates many of the angiogenic actions of vascular endothelial growth factor. Although sGC is expressed in the endothelium, its autocrine actions have not been thoroughly studied. Herein, we have investigated the role of sGC in neo-vessel formation using the chicken chorioallantoic membrane (CAM) model of angiogenesis. Initially, we confirmed the presence of sGC subunits in the CAM during the time of maximal angiogenesis. Moreover, when cells transfected with a luciferase reporter gene under the control of the sGC α1 promoter were placed on the CAM, we observed that expression of this sGC subunit was higher at day 12 than day 6 (angiogenesis reaches its maximum at day 12 in the CAM). The existence of catalytically active sGC in the CAM was confirmed through the increase in cGMP tissue content after exposure to a NO donor (sodium nitroprusside). To study the role of sGC in angiogenesis we used several pharmacological agents that modulate cGMP levels in tissues (ODQ, a sGC inhibitor; BAY 41-2272, an NO-independent/heme-dependent activator of sGC; and zaprinast, a phosphodiesterase V inhibitor). ODQ inhibited angiogenesis in a dose-dependent manner, while BAY-41-2272 and zaprinast promoted neovascularization. We conclude that sGC activation promotes neo-vessel formation.

Original languageEnglish (US)
Pages (from-to)93-94
Number of pages2
JournalEpitheorese Klinikes Farmakologias kai Farmakokinetikes
Volume23
Issue number1
StatePublished - Mar 18 2005
Externally publishedYes

Fingerprint

Chorioallantoic Membrane
Nitric Oxide
Nitric Oxide Donors
Soluble Guanylyl Cyclase
Endothelial Cells
Type 5 Cyclic Nucleotide Phosphodiesterases
Phosphodiesterase Inhibitors
Nitroprusside
Luciferases
Heme
Reporter Genes
Vascular Endothelial Growth Factor A
Endothelium
Cell Movement
Chickens
Cell Proliferation
Pharmacology
Proteins

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Soluble guanylate cyclase activation promotes angiogenesis. / Pyriochou, Anastasia; Potytarchou, Christos; Papadimitriou, Evangelia; Papapetropoulos, Andreas.

In: Epitheorese Klinikes Farmakologias kai Farmakokinetikes, Vol. 23, No. 1, 18.03.2005, p. 93-94.

Research output: Contribution to journalArticle

Pyriochou, Anastasia ; Potytarchou, Christos ; Papadimitriou, Evangelia ; Papapetropoulos, Andreas. / Soluble guanylate cyclase activation promotes angiogenesis. In: Epitheorese Klinikes Farmakologias kai Farmakokinetikes. 2005 ; Vol. 23, No. 1. pp. 93-94.
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