Superfund Research Program
Superfund Chemicals, Nutrition, and Multi-Organ Cardiovascular Risk
Final Progress Reports
There is evidence that exposure to certain aromatic hydrocarbons, such as polychlorinated biphenyls (PCBs), can be implicated in the development of cardiovascular diseases such as atherosclerosis. Little is known about the mechanisms underlying the atherogenic potential of these aromatic hydrocarbons. Endothelial cell dysfunction is a critical event in the initiation and acceleration of atherosclerotic lesion formation. Because of its constant exposure to environmental contaminants and other blood components, including dietary lipids and prooxidants, the vascular endothelium is extremely vulnerable to chemical insult, as well as to necrotic and apoptotic injury. There is evidence that an increase in cellular oxidative stress and an imbalance in antioxidant status are critical events in PCB-mediated endothelial cell dysfunction. Project investigators propose that nutrition, and in particular dietary fat and antioxidant nutrients, can modify the atherogenic potential as well as cytotoxicity of PCBs. Results from this work will provide valuable information towards therapeutic nutrition intervention for populations at or near Superfund sites.
Researchers have demonstrated that PCBs, and especially PCBs which are AhR agonists, can activate vascular endothelial cells and that specific fats can further increase PCB-induced endothelial dysfunction, probably by contributing to oxidative stress and the production of toxic lipid metabolites. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress- or redox-sensitive transcription factors, which in turn can promote gene expression for inflammatory cytokines and adhesion molecules, and thus intensify an inflammatory response and endothelial cell dysfunction. Data also suggest that antioxidant nutrients (such as vitamin E) can protect against PCB-induced cell damage by interfering with signaling pathways of necrotic and apoptotic endothelial cell death.
These data provide evidence that nutrition can modulate the cytotoxicity of PCBs. The findings also suggest that diets high in antioxidant nutrients may protect against diseases of the vasculature, e.g., cardiovascular disease, which can be triggered by exposure to specific environmental contaminants such as PCBs.