# Endothelial Progenitor Cells and Particulate Air Pollution

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $613,222

## Abstract

ABSTRACT
Multiple epidemiological and experimental studies report that acute or chronic exposure to air pollution is
associated with adverse cardiovascular events including myocardial ischemia, stroke, arrhythmias, heart failure,
sudden cardiac arrest and atherogenesis. These effects of air pollution are most strongly correlated with fine
particulate matter (PM2.5) fraction which is generated directly from the combustion of fossil fuels and is found in
automobile exhaust, wood or coal smoke and industrial emissions. However, the mechanisms by which PM2.5
induces cardiovascular injury remain unclear and the pathophysiological conditions and co-exposures that
determine individual susceptibility to PM2.5 toxicity have not been identified. Our previous work has shown that
in young healthy adults, exposure to PM2.5 is associated with inflammation, decreases in vascular reparative
circulating angiogenic cells (CACs), and changes in cytokine/growth factor profiles consistent with an inhibition
of angiogenesis. In addition, we found increased levels of circulating endothelial microparticles, evidence of
subclinical vascular injury. We obtained similar results in mouse exposure studies, which show that exposure to
concentrated ambient particles depletes circulating angiogenic cells, and leads to defective hematopoiesis and
functional defects in bone marrow-derived cells. In pilot experiments, we have found that these PM2.5-induced
defects in mice could be prevented by treatment with the endogenous nucleophile carnosine, which quenches
reactive oxygen species and removes toxic products of lipid peroxidation. Furthermore, in a human cohort with
mild-to-moderate CVD risk, we also found that those with high CVD risk are more susceptible to the effects of
PM2.5 and that individuals with high carnosine levels are relatively impervious to the adverse cardiovascular
effects of PM2.5 exposure. Thus we hypothesize that individual risk factors determine cardiovascular susceptibility
to PM2.5 and that means to limit electrophiles/oxidative stress will mitigate the adverse consequences of PM2.5
exposure. These ideas will be tested in three Aims. In the first we will assess the impact of PM2.5 exposure on
vascular function (arterial stiffness, flow-mediated dilation, peripheral artery tone) in a population with mild-to-
moderate CVD risk and determine whether exposure exacerbates composite CVD risk and whether changes
inflammation, oxidative stress, or thrombosis are associated with PM2.5-induced vascular dysfunction. In the
second Aim, we will determine whether the relationship between vascular injury and dysfunction is mediated by
individual-level demographic characteristics (e.g., sex, age, ethnicity), co-exposure to gaseous pollutants, or
systemic levels of carnosine. In the third Aim, we will enroll a subset of individuals with inherently low carnosine
levels, and determine whether daily, oral supplementation with carnosine attenuates the association between
PM2.5...

## Key facts

- **NIH application ID:** 9899102
- **Project number:** 5R01ES019217-08
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Aruni Bhatnagar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $613,222
- **Award type:** 5
- **Project period:** 2011-09-23 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899102

## Citation

> US National Institutes of Health, RePORTER application 9899102, Endothelial Progenitor Cells and Particulate Air Pollution (5R01ES019217-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899102. Licensed CC0.

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