# Air pollution, atherosclerosis, and the role of the aryl hydrocarbon receptor

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $353,250

## Abstract

PROJECT SUMMARY
There is increasing evidence that exposure to air pollutants and ambient particulate matter (PM) elevates the
acute risk of mortality from atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is a chronic
inflammatory condition and the primary cause of ischemic heart disease and stroke, which are associated with
approximately 50% of all deaths in Western countries. Recent studies indicate that compared to crustal
sources of PM, vehicular-specific PM in urban areas, is more strongly associated with subclinical
atherosclerosis. PM generated by traffic-based fossil fuel combustion can contain significant amounts of
polycyclic aromatic hydrocarbons (PAHs), which studies show can activate the cytosolic aryl hydrocarbon
receptor (AhR) and contribute to PM-mediated atherogenesis. Recent work, including our own, implicates the
interaction of vehicular-specific PM with AhR as a key event leading to elevated levels of pro-inflammatory
cytokines and greater formation of foam cells and atherosclerotic plaques. Components of a high-fat diet, such
as elevated levels of saturated fatty acids and cholesterol, trigger activation of Nod-like receptor proteins
(NLRP)3/inflammasome in vascular tissue. Our work indicates linkages between the pathophysiology of AhR-
and NLRP3/inflammasome-mediated pathways as both PM from traffic-related air pollution (TRAP) and a high-
fat diet (HFD) contribute to the activation of immune cells and production of pro-inflammatory factors, which are
critically involved in atherogenesis. The central hypothesis is that the simultaneous activation and interaction of
AhR and NLRP3/inflammasome from TRAP exposure combined with a high-fat diet enhances vascular
inflammation and dysfunction in the aortic wall, which ultimately increases atherosclerosis. We believe that the
TRAP-mediated activation of AhR in macrophages and dendritic cells, along with blood lipids generated from a
high-fat diet, synergistically activate the NLRP3/inflammasome to induce pro-inflammatory marker genes and
atherosclerosis. This concept will be tested in C57BL/6 wt, Apoe-/-, Apoe-/-/AhR-/-, and Apoe-/-/NLRP3-/- mice. To
identify the mechanisms of TRAP-mediated atherosclerosis, we will examine the role of the AhR and NLRP3
receptor during activation of dendritic cells and macrophages. In addition, chemical components of TRAP will
be analyzed to identify those that cause cellular responses, such as induction of macrophage- and dendritic
cell-specific marker genes, which are critical mediators of atherosclerosis. The study is designed to identify the
mechanisms and key players that are responsible for promoting atherosclerosis through exposure to air
pollutants. New insight into the interacting role of the AhR with the NLRP3/inflammasome is critical to
understand how TRAP increases the risk of developing atherosclerosis.

## Key facts

- **NIH application ID:** 10540334
- **Project number:** 5R01ES029126-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** CHRISTOPH F A VOGEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $353,250
- **Award type:** 5
- **Project period:** 2019-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10540334

## Citation

> US National Institutes of Health, RePORTER application 10540334, Air pollution, atherosclerosis, and the role of the aryl hydrocarbon receptor (5R01ES029126-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10540334. Licensed CC0.

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