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

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.

LanguageEnglish
Pages329-337
Number of pages9
JournalThrombosis and Haemostasis
Volume113
Issue number2
Early online date30 Oct 2014
DOIs
Publication statusPublished - 1 Feb 2015

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Carbon Monoxide
Phosphorylation
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Autacoids
Human Umbilical Vein Endothelial Cells
Therapeutic Uses
Cell Movement
Blood Vessels
Actins
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Gases
Cell Proliferation

Keywords

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

Cite this

Ahmad, Shakil ; Hewett, Peter W. ; Fujisawa, Takeshi ; Sissaoui, Samir ; Cai, Meng ; Gueron, Geraldine ; Al-Ani, Bahjat ; Cudmore, Melissa ; Ahmed, S. Faraz ; Wong, M.K.K. ; Wegiel, Barbara ; Otterbein, Leo E. ; Vítek, Libor ; Ramma, Wenda ; Wang, Keqing ; Ahmed, Asif . / Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation. In: Thrombosis and Haemostasis. 2015 ; Vol. 113, No. 2. pp. 329-337.
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Ahmad, S, Hewett, PW, Fujisawa, T, Sissaoui, S, Cai, M, Gueron, G, Al-Ani, B, Cudmore, M, Ahmed, SF, Wong, MKK, Wegiel, B, Otterbein, LE, 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, vol. 113, no. 2, pp. 329-337. https://doi.org/10.1160/TH14-01-0002

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation. / Ahmad, Shakil; Hewett, Peter W.; Fujisawa, Takeshi; Sissaoui, Samir; Cai, Meng; Gueron, Geraldine; Al-Ani, Bahjat; Cudmore, Melissa; Ahmed, S. Faraz; Wong, M.K.K.; Wegiel, Barbara; Otterbein, Leo E.; Vítek, Libor; Ramma, Wenda; Wang, Keqing; Ahmed, Asif .

In: Thrombosis and Haemostasis, Vol. 113, No. 2, 01.02.2015, p. 329-337.

Research output: Contribution to journalArticle

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AU - Ahmad, Shakil

AU - Hewett, Peter W.

AU - Fujisawa, Takeshi

AU - Sissaoui, Samir

AU - Cai, Meng

AU - Gueron, Geraldine

AU - Al-Ani, Bahjat

AU - Cudmore, Melissa

AU - Ahmed, S. Faraz

AU - Wong, M.K.K.

AU - Wegiel, Barbara

AU - Otterbein, Leo E.

AU - Vítek, Libor

AU - Ramma, Wenda

AU - Wang, Keqing

AU - Ahmed, Asif

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