cGMP-dependent and -independent angiogenesis-related properties of nitric oxide

Anastasia Pyriochou, Theodoros Vassilakopoulos, Zongmin Zhou, Andreas Papapetropoulos

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Nitric oxide exerts a stimulatory role during postnatal angiogenesis. Although soluble guanylyl cyclase (sGC) mediates many of the effects of nitric oxide (NO) in the vascular system, the contribution of cGMP-dependent vs cGMP-independent pathways in NO-induced angiogenesis remains unclear. Herein, we determined the effects of a NO donor (sodium nitroprusside; SNP) and a NO-independent sGC activator (BAY 41-2272) in the growth and migration of rat aortic endothelial cells (RAEC). RAEC lack enzymatically active sGC as suggested by their inability to accumulate cGMP upon exposure to SNP. However, treatment of RAEC with SNP promoted a modest increase in their proliferation and migration that was dependent on extracellular signal regulated kinase1/2 activation. Moreover, when RAEC were exposed to vascular endothelial growth factor we observed an increase in migration that was inhibited by NO synthase, but not sGC, inhibition. Infection of cells with adenoviruses containing sGC greatly increased the efficacy of SNP as a mitogenic and migratory stimulus. We conclude that NO is capable of stimulating EC proliferation and mobility in the absence of sGC; however, increased intracellular levels of cGMP following sGC activation greatly amplify the angiogenic potential of NO.

Original languageEnglish (US)
Pages (from-to)1549-1554
Number of pages6
JournalLife Sciences
Volume81
Issue number21-22
DOIs
StatePublished - Nov 10 2007
Externally publishedYes

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Keywords

  • cGMP
  • Guanylyl cyclase angiogenesis
  • Migration
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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