Projects | Endothelial Cell Dysfunction

BerniePearson
Dr. Kevin Pearson and Dr. Bernhard Hennig

Bernhard Hennig (Project Leader)
Kevin Pearson

PROJECT DESCRIPTION

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 and hypertriglyceridemia. Superfund chemicals, and especially persistent organic pollutants such as PHAs and PCBs, also have been shown to increase the risk and incidence of cardiovascular diseases. Most of all, we have evidence that both selected PCBs and fatty acids can induce endothelial cell dysfunction and inflammation, critical events in the early pathology of atherosclerosis. Our data suggest that diet, nutrition, and life-style changes can modify pathologies of chronic diseases, as well as diseases associated with environmental toxic insults.

Little is known about mechanisms and regulation of cellular uptake, trafficking and initiation of proinflammatory pathways by both PCBs and fatty acids. Membrane lipid rafts such as caveolae are particularly abundant in endothelial cells, where they are believed to play a major role in the regulation of endothelial vesicular trafficking. Thus, we hypothesize that caveolae are critical in the cellular uptake of selected fatty acids and lipophilic environmental contaminants such as PCBs. Caveolae have also been implicated in the regulation of cell signal transductions. We further hypothesize that PCBs and certain dietary lipids interact with caveolae and trigger distinct proatherogenic signaling pathways, leading to endothelial cell dysfunction. We also hypothesize that these signaling pathways can be down-regulated by antioxidant nutrients and related bioactive compounds (e.g., diet-derived flavonoids) as well as by ligands of antiatherogenic nuclear receptors (PPARs).

These hypotheses are being tested in vitro as well as in vivo by studying the interactions of PCBs with dietary compounds such as fatty acids and antioxidants. Importantly, we will use cell and mouse models lacking the caveolin gene to determine the involvement of caveolae in the PCB and fatty acid uptake and toxicity. We propose to explore mechanisms of nutrient-mediated modulation of PCB toxicity, and the outcome of our proposed study may lead to novel nutritional recommendations and therapeutic interventions in populations exposed to Superfund chemicals.

PROJECT POSTERS AND PRESENTATIONS

    UK Superfund Research Student Maggie Murphy

    Research conducted by Maggie Murphy, a fourth-year Ph.D. student under Bernhard Hennig, director of the University of Kentucky Superfund Research Center (UK-SRC), has shown that PCBs can induce atherosclerosis, a leading cause of cardiovascular disease. PCBs (polychlorinated biphenyls) -- a class of hazardous chemicals used in coatings for electronics, sealants, adhesives, paint, and flame retardant's were banned in the 1970s but these toxic compounds continue to linger in groundwater and soil.
    Murphy’s cell-culture and whole-animal research shows that antioxidants can prevent PCB-induced signaling which leads to inflammation, and ultimately atherosclerosis.

    Her next step: exploring lifestyle changes such as running as a therapy for PCB exposure. An avid marathoner, Murphy enjoys being able to combine her love of running and her passion for research in her quest to see if exercise is a therapeutic treatment against chemical insults.

    UK Superfund Student Maggie Murphy from Reveal on Vimeo.

    UK Superfund Research Student Brad Newsome

    Fifth-year graduate student Brad Newsome is developing composite nanomaterials for sensing and capture of PCBs, toxic compounds at Superfund sites in Kentucky and around the world. Polychlorinated biphenyls (PCBs) -- a class of hazardous chemicals used in coatings for electronics, sealants, adhesives, paint, and flame retardants -- were banned in the 1970s, but these toxic compounds continue to linger in groundwater and soil.

    Newsome’s research focuses on creating a nontoxic way to address pollution by incorporating membrane filtration and magnetic separation with natural antioxidant polymers that bind organic pollutants. He is taking this research to Southeast Asia, through the Fulbright program, where he will develop water remediation techniques to deal with the rapid production of environmental pollutants in Cambodia.

    UK Superfund Student Brad Newsome from Reveal on Vimeo

 

PROJECT STUDENT & POSTDOCTORAL RESEARCHERS

Katryn Eske Sung Gu Han, Ph.D. Brittany Meyer
     
Maggie Murphy

Brad Newsome

Michael Petriello


 

 

THE ENDOTHELIAL PROJECT RESEARCH TEAM

 

 

 

 
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