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TARGETS AND TARGETING OF IMMUNOMETABOLISM IN CHRONIC PM2.5 EXPOSURE

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Principal Investigator: Maiseyeu, Andrei
Institute Receiving Award Case Western Reserve University
Location Cleveland, OH
Grant Number R01ES033670
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 07 Feb 2022 to 30 Nov 2026
DESCRIPTION (provided by applicant): Project Summary PM2.5 is a leading global risk factor for morbidity and mortality and is the leading environmental factor implicated in cardiovascular disease. Recent data suggest that PM2.5 and/or traffic-related air pollutants may play a role in chronic diseases such as Type 2 diabetes mellitus, that may in turn confer susceptibility to cardiovascular disease and has been the topic of multiple systematic reviews and meta-analysis by us and others. In a series of studies in animals and humans, we have provided convincing evidence linking PM2.5 to pathways playing an etiologic role in cardiometabolic disease. Our findings and reviews have fundamentally shaped the understanding of the effects of PM2.5 and its association with increased risk of cardiometabolic disease. In particular, our group has demonstrated pro-atherogenic effects of chronic PM2.5 exposure, through ROS and inflammation dependent pathways. Although our understanding of pathways contributing to progression of disease has been dramatically enhanced, the mechanisms involved in the resolution of inflammation and an understanding of how dysregulation of resolution pathways contributes to disease progression has been limited. Identification of these mechanisms could pave the way for new opportunities to target non only air pollution mediated cardiovascular risk but other pervasive health risks. Through the implementation of three specific aims this proposal seeks to: 1) characterize air pollution-induced changes in inflammation resolution pathways; 2) determine to what extent these pathways overlap with dietary manipulation; 3) identify potential intervention strategies to promote upregulation of conserved resolution pathways in response to air pollution-induced inflammation.
Science Code(s)/Area of Science(s) Primary: 69 - Respiratory
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Srikanth Nadadur
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