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

Research output: Contribution to journalArticle

Authors

  • Shakil Ahmad
  • Samir Sissaoui
  • Geraldine Gueron
  • Barbara Weigel
  • Syed Faraz Ahmed
  • M. K. K. Wong
  • Leo Otterbein
  • Libor Vitek
  • Wenda Ramma
  • Ke-Qing Wang
  • Asif Ahmed

External organisations

  • First Faculty of Medicine, Charles University, Prague, Czech Republic
  • Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  • Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA;
  • Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
  • University of Edinburgh
  • University of Liverpool
  • University of Southern California, USC / Norris Comprehensive Cancer Center, Los Angeles, California, USA
  • Charles Univ
  • Aston Medical Research Institute, Aston Medical School, Aston Triangle, Birmingham, West Midlands B4 7ET, UK

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.

Details

Original languageEnglish
Article numberdoi: 10.1160/TH14-01-0002
Pages (from-to)329-337
Number of pages8
JournalThrombosis and Haemostasis
Volume113
Issue number2
Publication statusPublished - Feb 2015

Keywords

  • Carbon monoxide; angiogenesis; endothelial cells; vascular endothelial growth factor; vascular endothelial growth factor receptor-2