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Thromb Haemost 2015; 113(02): 329-337
DOI: 10.1160/TH14-01-0002
Endothelium and Angiogenesis
Schattauer GmbH

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

Shakil Ahmad
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
,
Peter W. Hewett
2   Department of Reproductive and Vascular Biology, Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
,
Takeshi Fujisawa
2   Department of Reproductive and Vascular Biology, Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
,
Samir Sissaoui
2   Department of Reproductive and Vascular Biology, Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
,
Meng Cai
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
,
Geraldine Gueron
3   Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Buenos Aires, Argentina
,
Bahjat Al-Ani
2   Department of Reproductive and Vascular Biology, Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
,
Melissa Cudmore
2   Department of Reproductive and Vascular Biology, Institute of Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Birmingham, UK
,
Faraz S. Ahmed
4   School of Medicine, University of Liverpool, Liverpool, UK
,
Michael K. K. Wong
5   University of Southern California, USC / Norris Comprehensive Cancer Center, Los Angeles, California, USA
,
Barbara Wegiel
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
6   Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
,
Leo E. Otterbein
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
6   Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
,
Libor Vítek
7   First Faculty of Medicine, Charles University, Prague, Czech Republic
,
Wenda Ramma
6   Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
,
Keqing Wang
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
,
Asif Ahmed
1   Vascular and Obstetric Biology Laboratory, Aston Medical School, Aston University, Birmingham, UK
› Author Affiliations
Further Information

Publication History

Received: 02 January 2014

Accepted after major revision: 24 September 2014

Publication Date:
27 November 2017 (online)

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Referred to by:

Erratum to Loboda et al. “Carbon monoxide: pro- or anti-angiogenic agent? Comment on Ahmad et al. (Thromb Haemost 2015; 113: 329–337)Thromb Haemost 2016; 116(07): 203
DOI: 10.1160/TH16070001

Summary

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.

Keywords

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

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