# Identifying the Molecular Mechanisms of Air Pollution-Induced Thrombosis

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $37,402

## Abstract

Project Summary:
Particulate matter (PM) air pollution is a common promoter for the development of thrombosis and cardiovascular
disease. Specifically, exposure and deposition of PM in the alveolar capillary region (ACR) of the lung promotes
thrombosis through platelet activation, impaired fibrinolysis, and increased coagulation factor production;
however, the molecular mechanisms producing these adverse effects following PM exposure remain unclear.
Our goal is to identify the vascular endothelium's role in promoting these thrombotic effects and elucidate the
molecular mechanisms that result in a pro-thrombotic endothelium. To do this we have developed an organotypic
in vitro model of the ACR in which we expose alveolar epithelial cells within the model to PM and determine the
trans-epithelial (TE) effect in the underlying endothelial cells within the model. Our preliminary data suggests this
TE exposure induces endothelial redox dysfunction, decreases the expression of anti-coagulant and fibrinolytic
genes, and increases the expression of procoagulant genes. Our central hypothesis is TE exposure-induced
redox dysfunction activates a pro-thrombotic endothelium by alternatively regulating the NF-κB and MAPK
pathways. To test this hypothesis, our first aim is to define the relationship between the induced endothelial
redox dysfunction and the activation of a pro-thrombotic endothelium. To define this relationship, we will compare
the kinetics of redox dysfunction with the temporal expression of pro-thrombotic targets identified in our
preliminary data and with the kinetics of functional thrombotic endpoints. Antioxidant intervention studies will
then be performed to determine whether TE exposure-induced redox dysfunction drives the activation of a pro-
thrombotic endothelium. Our second aim is to determine how the NF-κB and MAPK signaling pathways activate
a thrombotic endothelium following a TE exposure. To determine these pathways' role we will evaluate the
activation of the NF-κB, c-Jun N-terminal kinase (JNK), and p38 signaling pathways and will assess promoter
binding at the activated pro-thrombotic targets of the downstream transcription factors of these pathways, p65,
c-Fos/c-Jun, and ATF-2. Antioxidant intervention studies will then be performed to determine if TE-induced redox
dysfunction mediates the activation of a pro-thrombotic endothelium by alternatively regulating these cellular
pathways. The molecular mechanisms identified upon completion of these aims will help elucidate the vascular
endothelium's role in promoting PMI-thrombosis. With these results, preventative and therapeutic strategies
against PMI-thrombosis and related cardiovascular diseases can be developed. Completion of these aims will
advance my training as a molecular toxicologist and support my development into a successful principal
investigator.

## Key facts

- **NIH application ID:** 9992859
- **Project number:** 1F31ES031854-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Eva Vitucci
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,402
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992859

## Citation

> US National Institutes of Health, RePORTER application 9992859, Identifying the Molecular Mechanisms of Air Pollution-Induced Thrombosis (1F31ES031854-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992859. Licensed CC0.

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