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University of Louisville

Superfund Research Program

Environmental Exposure and Cardiometabolic Disease

Project Leader: Craig J. McClain
Co-Investigators: Matthew C. Cave, Aruni Bhatnagar, Rachel J. Keith
Grant Number: P42ES023716
Funding Period: 2017-2022

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Project Summary (2017-2022)

The overall goal of this project within the University of Louisville Superfund Research Program (UL SRP) Center is to examine whether exposure to environmental pollutants, specifically volatile organic compounds (VOCs), induces or exacerbates cardiometabolic disease (CMD) by causing systemic insulin resistance and low-grade inflammation. Insulin is a master regulator of metabolism and energy disposition, and dysregulation of insulin signaling is associated with the development of obesity and Type 2 diabetes (T2D), which are robust contributors to atherogenesis and heart disease. Recent research has identified a pathogenic continuum between the development of insulin resistance, hepatic steatosis, dyslipidemia and cardiovascular disease.

To determine whether exposure to VOCs, including trichloroethylene (TCE), xylene, benzene, and acrolein exacerbates or induces insulin resistance and low-grade inflammation, the researchers are determining the impact of VOC exposure on insulin resistance, and subsequent CMD, in a prospective longitudinal study. They are examining the effects of low-level exposures to VOCs on CMD risk and progression in 500 participants with different levels of VOC exposure. The participants are enrolled from three geographic clusters identified as VOC "hotspots," including the Lee’s Lane Superfund site, from a previous analysis of 523 participants in the Louisville Healthy Heart Study.

The researchers are also examining whether VOC exposure is associated with elevated cardiovascular disease (CVD) risk, prevalence, and progression. They are evaluating how residential proximity to a VOC "hotspot" affects the progression of various indices of CVD injury and risk in the target population, and how these effects differ from those due to background VOC exposures in urban residential locations. They are also investigating the effect of VOCs on fatty liver disease. The finding of the project will be essential for developing exposure-response relationships and for identifying specific cardiovascular and cardiometabolic processes sensitive to VOC exposure.

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