Epidemiological and experimental studies suggest an association between elevated serum levels of co-planar
PCBs and
hypertension, and one study indicate that this effect is dependent on the level of oestrogen. This study investigated the effects of
3,3',4,4',5-pentachlorobiphenyl (
PCB126) and 17β-oestradiol (E₂) on vasoactive factors in human umbilical vein endothelial cells (HUVEC). The results reveal that
PCB126 stimulated the vasoconstriction factors COX-2 and
PGF(2α) in HUVEC. An up-regulation of COX-2 expression was demonstrated using qRT-PCR, western blot and immunofluorescence and increased production of
PGF(2α) was demonstrated using LC/MS² and
enzyme immunoassay. Also,
PCB126 slightly increased ROS production and decreased NO production in HUVEC. The addition of E₂ enhanced PCB126-induced transcription of
CYP1A1, CYP1B1 and COX-2 in HUVEC whereas an increased transcription of eNOS only occurred following combined treatment with E₂ and
PCB126. Immunofluorescence demonstrated that HUVEC expressed AHR and ERβ but lacked ERα and the involvement of AHR and ERβ on the effects of
PCB126 was examined by the addition of AHR and ER antagonists. The binding of
PCB126 to AHR was critical for the effects of
PCB126 whereas the role of ERβ was equivocal. In conclusion, these studies suggest that
PCB126 induced changes in human endothelial cells that are characteristic for endothelial dysfunction in human
hypertension and that PCB126-induced transcription of genes important for vascular function in human endothelial cells can be elevated by increased oestrogen levels. These findings may help understanding the mechanism for the association between
PCB126 exposure and
hypertension reported in human subjects and experimental animals.