# Dissecting the Role of Arachidonic Acid Metabolic Pathways Involved in Resolution Versus Progression of PM-Induced Cardiometabolic Toxicity

> **NIH ES R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2026 · $401,491

## Abstract

PROJECT SUMMARY/ABSTRACT (AD-focused Administrative Supplement)
The estimated number of people with dementia is predicted to triple by 2050 worldwide. Together with the lack
of effective treatments to stop, slow or prevent Alzheimer’s disease (AD) and its related dementias, the best
strategy to limit the predicted incidence is to mitigate AD risk factors. Exposure to ambient particulate matter
(PM) is emerging as a modifiable environmental risk factor for AD. However, the mechanism by which PM
exposure contributes to the development of AD is not known. Our previous research has shown that exposures
to ultrafine particles (UFP) and diesel exhaust (DE) in mice lead to chronic inflammation, increased lipid
peroxidation in lung and systemic tissues, disturbances in lipid metabolism and plasma lipoproteins, and the
development of liver steatosis and atherosclerosis, all components of the commonly called cardiometabolic
syndrome. Recent studies suggest that cardiovascular and metabolic disorders may play a critical role in the
development of AD. In fact, AD and cardiometabolic syndrome share major risk factors, in addition to
cerebrovascular and cardiovascular changes occurring years before symptoms occur. We will augment the
Parental R01 (ES033703, RESTORE RFA) by extending its focus on hepatic steatosis and atherosclerosis with
the analyses of brain tissue in the same hyperlipidemic mouse model (low-density lipoprotein knockout, Ldlr KO),
placed on a high fat diet (HFD). Importantly, Ldlr deficiency and HFD administration have been associated with
worsened AD-related phenotypes and cognitive dysfunction in a transgenic mouse model of AD through
impairment of antioxidant system defenses leading to oxidative stress and neuronal apoptosis. Therefore, while
this is not a typical mouse model for the study of AD, we do expect significant neuroinflammatory and
neurodegenerative effects. Our overall objective is to identify critical pathways in the Lung-Heart-Brain Axis
that co

## Key facts

- **NIH application ID:** 11300060
- **Project number:** 3R01ES033703-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jesus Antonio Araujo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ES
- **Fiscal year:** 2026
- **Award amount:** $401,491
- **Award type:** 3
- **Project period:** 2022-02-11T00:00:00 → 2026-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11300060

## Citation

> US National Institutes of Health, RePORTER application 11300060, Dissecting the Role of Arachidonic Acid Metabolic Pathways Involved in Resolution Versus Progression of PM-Induced Cardiometabolic Toxicity (3R01ES033703-05S1). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11300060. Licensed CC0.

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