# E-cigarette Nicotine Induces Epigenetic Changes in Vascular Cells

> **NIH VA I01** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2024 · —

## Abstract

Abdominal aortic aneurysm (AAA) is a common life-threatening condition in which progressive enlargement of
the infrarenal aorta can lead to rupture and death. AAA is responsible for approximately 41,000 deaths world-
wide annually, but there are no medical therapies that prevent AAA development, rupture, or aneurysm-related
death. The major epidemiological risk factors for AAA include, male sex, advanced age, genetic predilection and
a history of tobacco use. As such, it is not surprising that an estimated 350,000 Veterans within the VHA suffer
from AAA. The most significant modifiable risk factor associated with AAA is tobacco use, but the molecular
links behind this relationship remain unclear, and there is currently minimal information about the effects of e-
cigarettes on AAA. Our lab has recently shown that nicotine vaping enhances vascular oxidative stress and
inflammatory gene expression, and leads to accelerated murine model AAA. Combined experimental and in
silico analyses suggest that nicotine induces alterations in the vascular epigenetic landscape, priming cells for
inflammatory gene expression and augmenting AAA development. Preliminary single-cell RNA sequencing
experiments demonstrate that inhaled nicotine results in pro-inflammatory transcriptomic alterations in genes
from multiple cell sub-populations. In our first Aim, we will delineate the cell type-specific effects of inhaled
nicotine on chromatin remodeling and on gene expression at single cell resolution in murine model AAA using
combined sc-RNAseq, sc-ATAC-seq, and sc-ChIP-seq analyses of aortic tissue throughout the time course of
AAA development. Pathway analysis will identify programs involved in AAA development, particularly seeking
out initiation and propagation events. Next, we will evaluate the effects of nicotine on epigenetic characteristics
and phenotypic function of AAA-relevant cells in vitro. We will perform pharmacological and genetic
manipulations in cell culture, prioritizing identified signals that appear to have beneficial effects upon vascular
inflammation and cellular integrity. Finally, we will examine the therapeutic impact of inhibiting nicotine-induced
epigenetic changes in our established mouse models of AAA. We will examine aneurysm development and
growth, as well as the effects of such therapies on gene expression in aortic cell subtypes, and the aortic
epigenetic environment. This work will provide novel insights into how nicotine alters the epigenetic landscape
of vascular cells, and predisposes towards AAA development, providing a basis for future research and
suggesting new translational therapeutic targeting strategies. Moreover, given the role of inflammation in many
tobacco-related diseases, these studies could have implications for addressing the broader health effects of
chronic smoking, e-cigarette use and vaping. Further, this work may provide a blueprint for studying the health
effects of exposure to other environmental toxins.

## Key facts

- **NIH application ID:** 10807427
- **Project number:** 1I01BX006438-01
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** Philip S Tsao
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807427

## Citation

> US National Institutes of Health, RePORTER application 10807427, E-cigarette Nicotine Induces Epigenetic Changes in Vascular Cells (1I01BX006438-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10807427. Licensed CC0.

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