Bisphenol A induces a pro-angiogenic-like phenotype via the G protein-coupled receptor 30 (GPR30) pathway

Endocrine disruptors (EDs) are a group of environmental contaminants known to interfere with hormonal signaling. Among them, Bisphenol A (BPA) widely used in plastic manufacturing enters human bodies mainly through ingestion of contaminated water or food. Elevated circulating BPA levels have been associated with cardiovascular diseases (CVDs) suggesting a potential role in endothelial dysfunction. Thus, the aim of this study was to investigate the effects of BPA on human endothelial cells. Human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells (HAEC) were exposed to BPA for different time intervals. Effects on cell viability, pro-angiogenic-like capacity, vascular remodeling and intracellular signaling pathways were evaluated. BPA exposure significantly enhanced tube formation and upregulated the expression of the pro-angiogenic factor cyclooxygenase-2 (COX2), as well as of adhesion molecules, specifically vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In addition, BPA increased the protein expression level of the non-classical estrogen receptor G-protein coupled receptor 30 (GPR30) in both cell types. Of note, pharmacological inhibition of GPR30 counteracted the BPA-induced pro-angiogenic-like response, supporting the involvement of GPR30 in the pro-angiogenic-like effects of BPA.