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Proangiogenic effects of environmentally relevant levels of bisphenol A in human primary endothelial cells

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Abstract

Bisphenol A (BPA) is widely used in the manufacturing of consumer products such as plastic food containers and food cans. Experimental studies suggest a relationship between exposure to BPA and changes in metabolic processes and reproductive organs. Also, epidemiological studies report an association between elevated exposure to BPA and cardiovascular disease and diabetes. Although alterations in the vascular endothelium are implicated in pathological conditions associated with BPA, little is known about the effects of BPA in the human endothelium. This study aimed to investigate the effects of 0.1 nM–1 μM of BPA on selected biomarkers of endothelial dysfunction, inflammation, and angiogenesis in human umbilical vein endothelial cells (HUVEC). The mRNA expression of biomarkers was assayed using qRT-PCR, and the production of nitric oxide and reactive oxygen species was measured using the H2DCFDA and the DAF-FM assays. The effect of BPA on phosphorylated eNOS was examined using Western blot and immunofluorescence, and the endothelial tube formation assay was used to investigate in vitro angiogenesis. BPA (≤1 μM) increased the mRNA expression of the proangiogenic genes VEGFR-2, VEGF-A, eNOS, and Cx43 and increased the production of nitric oxide in HUVEC. Furthermore, BPA increased the expression of phosphorylated eNOS and endothelial tube formation in HUVEC. These studies demonstrate that environmentally relevant levels of BPA have direct proangiogenic effects on human primary endothelial cells in vitro suggesting that the human endothelium may be an important target for BPA.

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Acknowledgments

Thanks to Professor Björn Hellman for invaluable help with the preparation of manuscript and Raili Engdahl, Lena Norgren, Ida Jakobsson, and Fanar Sliwa for excellent technical assistance. We also thank The Swedish Research Council Forskningsrådet för miljö, areella näringar och samhällsbyggande (FORMAS) for funding.

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The authors declare that there are no conflicts of interest.

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  1. Department of Pharmaceutical Biosciences, Uppsala University, P. O. Box 591, SE-75124, Uppsala, Sweden

    Helén Andersson & Eva Brittebo

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  1. Helén Andersson
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  2. Eva Brittebo
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Correspondence to Eva Brittebo.

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Andersson, H., Brittebo, E. Proangiogenic effects of environmentally relevant levels of bisphenol A in human primary endothelial cells. Arch Toxicol 86, 465–474 (2012). https://doi.org/10.1007/s00204-011-0766-2

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