Journal Article

Benzo[<i>a</i>]pyrene Inhibits Angiogenic Factors–Induced αvβ3 Integrin Expression, Neovasculogenesis, and Angiogenesis in Human Umbilical Vein Endothelial Cells

Ching-Hao Li, Yu-Wen Cheng, Yao-Teng Hsu, Yu-Jeng Hsu, Po-Ling Liao and Jaw-Jou Kang

in Toxicological Sciences

Volume 118, issue 2, pages 544-553
Published in print December 2010 | ISSN: 1096-6080
Published online September 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq279
Benzo[a]pyrene Inhibits Angiogenic Factors–Induced αvβ3 Integrin Expression, Neovasculogenesis, and Angiogenesis in Human Umbilical Vein Endothelial Cells

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New blood vessel formation is necessary for the repair of ischemia-damaged tissues. Endothelial cells produce exogenous and endogenous angiogenic factors in the mediation of angiogenesis and neovasculogenesis during neovascularization. Exposure to environmental pollutants may alter proangiogenic capacity or desensitize the responses of endothelial cells to stimulation by basic fibroblast growth factor and vascular endothelial growth factor. Human umbilical vein endothelial cells (HUVECs) were pretreated with benzo[a]pyrene (B[a]P), the major carcinogenic constituent found in tobacco smoke, for 24 h. Neovasculogenesis, migration, and proliferation were evaluated in solvent-treated and B[a]P-treated HUVECs. Endothelial capillary-like tube formation, cell migration, mitogen-activated protein kinase (MAPK) phosphorylation, and integrin expression were reduced in B[a]P-treated HUVECs with angiogenic factor stimulation, in comparison to solvent-treated HUVECs, although cell proliferation and Akt activation remained unaffected. Inhibition of B[a]P-mediated MAPK and neovasculogenesis was significantly rescued by pretreatment with α-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist. The B[a]P-mediated inhibition of neovasculogenesis was also rescued in AhR-silenced HUVECs, suggesting the requirement for AhR in B[a]P-associated effects. B[a]P also inhibited angiogenesis in a chorioallantoic membrane assay. We conclude that B[a]P is a potent inhibitor of angiogenesis, and its effects are mediated via AhR-dependent phenotypic changes in B[a]P-treated HUVECs. These findings contribute to an understanding of the involvement of AhR agonists in vasculotoxicity.

Keywords: angiogenesis; benzo[a]pyrene; neovasculogenesis; endothelial cells; integrins

Journal Article.  4302 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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