Bisphenol A promotes X-linked inhibitor of apoptosis protein-dependent angiogenesis via G protein-coupled estrogen receptor pathway

Bisphenol A (BPA), one of the high-volume chemicals worldwide, has a core structure resembling that of natural estradiol. Recent evidence has demonstrated that exposure to BPA has a relationship with the risk of cancer. The objective of our study is to investigate the mechanisms underlying the pro-angiogenic effects of BPA. We demonstrated that BPA markedly induces endothelial cell proliferation, migration and tube formation by activating endothelial nitric oxide synthase. BPA-induced nitric oxide generation appeared to be associated with the X-linked inhibitor of apoptosis protein (XIAP), which competes with endothelial nitric oxide synthase for caveolin-1. BPA was shown to exert its pro-angiogenic effect by upregulating XIAP expression via G protein-coupled estrogen receptor (ER) activation but not via ER or ER. Our data suggest that 100nM BPA promote angiogenesis in a G protein-coupled ER-dependent genomic pathway, and provide a novel insight into the potential role of XIAP in mediating the pro-angiogenic effects of BPA in endothelial cells. Copyright (c) 2015 John Wiley & Sons, Ltd. Our study investigates the mechanisms underlying the pro-angiogenic effects of bisphenol A (BPA). We demonstrated that BPA markedly induces endothelial cell proliferation, migration and tube formation by activating endothelial nitric oxide synthase. BPA-induced nitric oxide generation appeared to be associated with X-linked inhibitor of apoptosis protein, which competes with endothelial nitric oxide synthase for caveolin-1. BPA was shown to exert its pro-angiogenic effect by upregulating X-linked inhibitor of apoptosis protein expression via G protein-coupled estrogen receptor activation but not via estrogen receptor ER or ER.