# Vascular Toxicity of Benzene

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2024 · $664,616

## Abstract

Abstract:
Benzene is a ubiquitous environmental pollutant. Natural sources of benzene include gas
emissions from volcanos and forest fire. Benzene is also one of the top 20 chemicals generated
by industrial sources in the United States. While levels of benzene in the ambient air are usually
in low ppb range, amount of benzene in automobile exhaust and tobacco smoke can exceed 50
ppm, and occupational exposure to benzene can be as high as several hundred ppm. People
living near hazardous waste sites, gasoline refineries, petrochemical industries, and gasoline
fueling stations may also have high exposure to benzene. Emerging data suggest that benzene
can exert cardiovascular toxicity. Our preliminary studies show that exposure to benzene
exacerbates atherosclerosis, the underlying cause of most cardiovascular disease and stroke. In
vitro studies show that benzene metabolite t,t-muconaldehyde induces endothelial activation
(expression of adhesion molecules, leukocyte adhesion and their trans-endothelial migration, and
endothelial cell apoptosis). Using RNA-seq approach, we identified several molecular targets
(eNOS, SOD1, HO-1, COX-2, ATF3 etc.) by which benzene and its metabolites can exert adverse
effects on endothelial functions. We also observed that heat shock proteins HSPA1A and
HSPA1B induced by benzene exposure could play a protective role in benzene-induced
endothelial dysfunction and atherosclerosis. Based on these observations, we hypothesize that
HSPA1A and HSPA1B prevent benzene-induced exacerbation of atherogenesis by inhibiting
vascular inflammation and injury. To test this hypothesis, we propose two specific aims: Aim 1
will examine how HSPA1A and HSPA1B affect benzene-induced endothelial functions (vascular
relaxation, leukocyte rolling and adhesion to vascular endothelium, apoptosis) and Aim 2 will
examine how endothelial cell specific overexpression of HSPA1A and HSPA1B affects benzene-
induced atherosclerosis (lesion size, composition and nature). Successful completion of this
project will establish a mechanistically validated model of benzene-induced endothelial
dysfunction and atherosclerosis. This will provide a strong rationale to examine the association of
benzene exposure with vascular dysfunctions and atherosclerosis in humans.

## Key facts

- **NIH application ID:** 10803764
- **Project number:** 1R01ES033531-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Sanjay Srivastava
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $664,616
- **Award type:** 1
- **Project period:** 2024-02-21 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803764

## Citation

> US National Institutes of Health, RePORTER application 10803764, Vascular Toxicity of Benzene (1R01ES033531-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10803764. Licensed CC0.

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