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University of Kentucky

Superfund Research Program

Superfund Chemicals, Nutrition, and Endothelial Cell Dysfunction

Project Leader: Bernhard Hennig
Co-Investigator: Michal Toborek (University of Miami)
Grant Number: P42ES007380
Funding Period: 1997-2020
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2008-2014)

Atherosclerosis, a chronic inflammatory disease, is still the number one cause of death in the United States. Numerous risk factors for the development of atherosclerosis have been identified, including obesity, hypertriglyceridemia, and exposure to Superfund chemicals, such as persistent organic pollutants (e.g., RGBs).

Plant-based bioactive food components are reported to have antioxidant and anti-inflammatory properties. Preliminary data suggests that endothelial cell dysfunction and inflammatory events induced by exposure to coplanar PCBs can be down-regulated by bioactive compounds, such as flavonoids; these events which can also be modified by the cellular lipid milieu. Little is known about mechanisms of nutritional modulation of environmental toxicity; however, membrane lipid domains, such as caveolae, are particularly abundant in endothelial cells, where they may play a major role in the regulation of endothelial vesicular trafficking. More recently, caveolae have also been implicated in the regulation of cell signal transductions; as a result, scientists hypothesize that caveolae are critical in the cellular responses to Superfund pollutants, lipids, and lipophilic bioactive compounds, such as flavonoids. They also hypothesize that the anti-inflammatory properties of flavonoids against chemical insults may be enhanced by omega-3 fatty acids and antagonized (or lessened by) omega-6 fatty acids. These hypotheses will be tested in vitro, as well as in vivo, by studying the interactions of PCBs with dietary components, such as fatty acids and flavonoids. Importantly, scientists will use cell and mouse models lacking the caveolin gene to determine the involvement of caveolae in inflammatory outcome. They propose to explore novel mechanisms of nutrient-mediated modulation of Superfund chemical toxicity, and the outcome of this proposed study will lead to novel nutritional recommendations and therapeutic interventions in populations exposed to Superfund chemicals. Superfund chemical exposure, specifically persistent organic pollutants like PCBs, has been linked to a heightened risk of cardiovascular disease to the public. This project intends to investigate the mechanisms used by these chemicals that result in disease, specifically, signaling pathways controlled by the membrane domains, caveolae. Furthermore, this project will focus on means of nutritional intervention by blocking these targets and, thus, proposing means of protecting the public from the harmful effects of Superfund chemical exposure.

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