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

被引：58

作者：

Ahmad, Shakil ^{[1
]}

Hewett, Peter W. ^{[2
]}

Fujisawa, Takeshi ^{[2
]}

Sissaoui, Samir ^{[2
]}

Cai, Meng ^{[1
]}

Gueron, Geraldine ^{[3
]}

Al-Ani, Bahjat ^{[2
]}

Cudmore, Melissa ^{[2
]}

Ahmed, S. Faraz ^{[4
]}

Wong, Michael K. K. ^{[5
]}

Wegiel, Barbara ^{[1
,6
]}

Otterbein, Leo E. ^{[1
,6
]}

Vitek, Libor ^{[7
]}

Ramma, Wenda ^{[6
]}

Wang, Keqing ^{[1
]}

Ahmed, Asif ^{[1
]}

机构：

[1] Aston Univ, Aston Med Sch, Vasc & Obstet Biol Lab, Birmingham B4 7ET, W Midlands, England

[2] Univ Birmingham, Coll Med & Dent, Dept Reprod & Vasc Biol, Inst Biomed Res, Birmingham, W Midlands, England

[3] Univ Buenos Aires, Sch Sci, Dept Biol Chem, IQUIBICEN CONICET, Buenos Aires, DF, Argentina

[4] Univ Liverpool, Sch Med, Liverpool L69 3BX, Merseyside, England

[5] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[6] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA

[7] Charles Univ Prague, Fac Med 1, Prague, Czech Republic

来源：

THROMBOSIS AND HAEMOSTASIS | 2015年 / 113卷 / 02期

基金：

英国医学研究理事会;

关键词：

Carbon monoxide; vascular endothelial growth factor; angiogenesis; endothelial cells; vascular endothelial growth factor receptor-2; NITRIC-OXIDE SYNTHASE; HUMAN HEME OXYGENASE; PROMOTES ANGIOGENESIS; MEDIATED ANGIOGENESIS; BASIC SCIENCE; GENE-TRANSFER; CELLS; VEGF; PROGRESSION; PROTEIN;

D O I：

10.1160/TH14-01-0002

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：329 / 337

页数：9

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