Exposure to polychlorinated biphenyls causes endothelial cell dysfunction.
Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery-derived endothelial cells were exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,4,4',5-pentachlorobiphenyl (PCB 114), or 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 and PCB 114 significantly disrupted, in a dose-dependent manner, endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. These PCBs also contributed markedly to cellular oxidative stress, as measured by 2,7-dichlorofluorescin (DCF) fluorescence and lipid hydroperoxides, and caused a significant increase in intracellular calcium ([Ca2+]i) levels. Enhanced oxidative stress and [Ca2+]i in PCB 77- and PCB 114-treated cells were accompanied by increased activity and content of cytochrome P450 1A and by a decrease in the vitamin E content in the culture medium. In contrast to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no effect on cellular oxidation, [Ca2+]i, or endothelial barrier function. These results suggest that certain PCBs may play a role in the development of atherosclerosis by causing endothelial cell dysfunction and a decrease in the barrier function of the vascular endothelium. It is possible that interaction of PCBs with the Ah receptor and activation of the cytochrome P450 1A subfamily are involved in this pathology.
Toborek
M
M
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054, USA.
Barger
S W
SW
Mattson
M P
MP
Espandiari
P
P
Robertson
L W
LW
Hennig
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013552:Swine; D014810:Vitamin E / Q000032:analysis
D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D002118:Calcium