# The role of the endothelium in vascular response to airborne PM.

> **NIH NIH R21** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2020 · $225,773

## Abstract

Project Summary
Increased levels of ambient particulate matter (PM) are consistently associated with cardiopulmonary and
cardiovascular morbidity and mortality. Despite the apparent health risk of exposure, surprisingly little is known
about the mechanisms underlying PM-mediated toxicity. PM emissions from a variety of combustion sources,
such as organic wastes, diesel, gasoline, wood and cigarettes, contain persistent free radicals often termed
environmentally persistent free radicals (EPFRs) due to their long half-lives in nature. EPFRs are a unique
particle-pollutant system capable of redox-cycling in air and soils for days to weeks, resulting in the generation
of reactive oxygen species. In our prior studies, we showed that inhalation of EPFRs decreased baseline
cardiac function, but these effects were secondary to changes in pulmonary vascular resistance. The
mechanism(s) underlying these vascular effects are as yet unknown; however, our preliminary data suggest
that EPFR-mediated activation of the aryl hydrocarbon receptor (AhR) in pulmonary epithelial cells results in
the release of vasoactive factors may play an important pathophysiological role. Our central hypothesis is
that EPFR-mediated activation of AhR at the air-blood interface and mobilization of vasoactive
mediators leads to activation/dysfunction of the pulmonary and systemic vasculature, resulting in
cardiovascular disease initiation and progression. To test this hypothesis, Specific Aim 1 will elucidate the
cellular mechanisms of vascular injury by testing whether EPFRs induce vascular dysfunction via activation of
the AhR, Floxed mice deficient in epithelial AhR compared to control littermate mice will be chronically exposed
to EPFRs, non-EPFR PM or filtered air by inhalation. Endothelium-dependent vascular reactivity, as well as
markers for both endothelial dysfunction and activation will be assessed. Specific Aim 2 will identify a putative
ligand promoting EPFR-induced AhR activation, and test whether this metabolite is associated with EPFR-
mediated vascular dysfunction. This aim will use both target and untargeted mass spectrometry approaches to
identify and characterize EFPR-induced lipid oxidation products that may serve as endogenous AhR agonists,
so that we may correlate tissue and blood levels of these metabolites with vascular dysfunction. Completion of
these aims will provide important new data linking EPFR-mediated oxidative stress, AhR activation, and
cardiovascular disease. This information will be critical for assessing risks to those living in proximity to
industrial or urban areas.

## Key facts

- **NIH application ID:** 9968406
- **Project number:** 5R21ES030062-02
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** TAMMY R DUGAS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,773
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968406

## Citation

> US National Institutes of Health, RePORTER application 9968406, The role of the endothelium in vascular response to airborne PM. (5R21ES030062-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9968406. Licensed CC0.

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