Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Shakil Ahmad, Peter W. Hewett, Takeshi Fujisawa, Samir Sissaoui, Meng Cai, Geraldine Gueron, Bahjat Al-Ani, Melissa Cudmore, S. Faraz Ahmed, M.K.K. Wong, Barbara Wegiel, Leo E. Otterbein, Libor Vítek, Wenda Ramma, Keqing Wang, Asif Ahmed*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

Original languageEnglish
Pages (from-to)329-337
Number of pages9
JournalThrombosis and Haemostasis
Volume113
Issue number2
Early online date30 Oct 2014
DOIs
Publication statusPublished - 1 Feb 2015

Keywords

  • angiogenesis
  • carbon monoxide
  • endothelial cells
  • vascular endothelial growth factor
  • vascular endothelial growth factor receptor-2

Fingerprint Dive into the research topics of 'Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation'. Together they form a unique fingerprint.

  • Cite this

    Ahmad, S., Hewett, P. W., Fujisawa, T., Sissaoui, S., Cai, M., Gueron, G., Al-Ani, B., Cudmore, M., Ahmed, S. F., Wong, M. K. K., Wegiel, B., Otterbein, L. E., Vítek, L., Ramma, W., Wang, K., & Ahmed, A. (2015). Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation. Thrombosis and Haemostasis, 113(2), 329-337. https://doi.org/10.1160/TH14-01-0002