Selected dietary lipids may increase the atherogenicity of environmental chemicals, such as polychlorinated biphenyls (PCB), by cross-amplifying mechanisms leading to dysfunction of the vascular endothelium. To investigate this hypothesis, cultured endothelial cells were treated with linoleic acid (18:2), followed by different PCB for up to 18 hours. Only PCB with Ah receptor binding activity disrupted endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. Prior cellular enrichment with 18:2 before PCB treatment further diminished endothelial barrier function, as compared to cells treated only with PCB. This phenomenon appears to be mediated by increased oxidative stress, which can be supported by enhanced DCF fluorescence, activation of NF-κB, as well as an observed decrease in vitamin E content in the culture media. Similar to the endothelial permeability data, pre-enrichment of cells with 18:2 further increased the PCB-mediated activity and content of cytochrome P450 1A. Our results suggest that certain unsaturated fatty acids can potentiate PCB-mediated endothelial cell dysfunction and that oxidative stress and activation of the cytochrome P450 1A subfamily may be in part responsible for these metabolic events. These findings have implications for understanding the involvement of certain environmental contaminants in diseases that involve dysfunction of the vascular endothelium.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology