The sprouting angiogenesis and vascular dysfunction triggered by bisphenol S and tetrabromobisphenol S through...

Exogenous chemical toxicants may be important inducers of pathological angiogenesis diseases. However, few studies have investigated the associations between pathological angiogenesis diseases and chemical toxicant exposures, and the specific mechanism by which chemical toxicants induce sprouting angiogenesis is unclear. In this study, zebrafish were exposed to bisphenol S (BPS, 1-100 microg/L) and tetrabromobisphenol S (TBBPS, 0.1 and 10 microg/L) from the embryonic stage to the larval stage to investigate how pollutants interfere with angiogenesis and the function of ectopic sprouting vessels. The results showed that BPS and TBBPS promoted ectopic sprouting angiogenesis in different types of vascular plexuses, including the posterior cardinal vein (PCV) and superficial choroidal vessels (SOVs), at different developmental time points. Proteomic analyses of eGFP-positive endothelial cells (ECs) isolated from Tg(flk1: eGFP) zebrafish revealed that both BPS and TBBPS induced ectopic angiogenesis by acting on vascular endothelial-cadherin (VE-cadherin) and activating downstream proangiogenic signaling. In ectopic sprouting vessels induced by BPS and TBBPS, increased endothelial permeability resulted in white blood cell recruitment. Human oxidized lipids also tended to deposit in these ectopic vessels following BPS and TBBPS exposure. These findings suggest that chemical toxicant-induced ectopic angiogenesis is an important cause of vascular dysfunction and related diseases.