# Benzene Exposure and Heart Failure

> **NIH NIH R21** · UNIVERSITY OF LOUISVILLE · 2022 · $234,750

## Abstract

Project Summary
Long-term exposure air pollutant exposure is recognized as a risk factor for cardiovascular diseases including
myocardial ischemia and heart failure. Recent epidemiological and experimental data indicate that many volatile
organic compounds including benzene contribute to worsening outcomes in patients with progressive heart
disease. Benzene is the most abundant air pollutant mostly generated from automobile exhaust and tobacco
smoke. Despite high prevalence of benzene in air-pollutants, little is known about the direct effects of inhaled
benzene on heart failure morbidity and mortality in well-controlled animal studies. Our recent studies show that
benzene exposure resembling moderate to high levels of human exposure worsens cardiac function in pressure
overload-induced mice. The benzene-induced worsening of cardiac functions was accompanied by endothelial
activation and infiltration of granulocytes in the heart and upregulation of gene expression for CXCL1 chemokine
and alarmin S100A8/A9 complex which promotes neutrophil and monocyte chemotaxis and adhesion through
TLR4 and RAGE signaling. Our new preliminary data show that ambient benzene exposure causes endothelial
activation/injury in humans and chronic low dose exposure stimulates endothelial activation/injury in mice. Using
animal model of pressure overload-induced cardiac dysfunction, we will examine the effects of environmental
benzene exposure on cardiac dysfunction (echocardiography, cardiac hypertrophy, analysis of composition and
activation status of infiltrating immune cells) during heart remodeling (Aim 1), and examine the molecular
mechanisms by which benzene exacerbate cardiac dysfunction (Aim 2). Successful completion of these studies
will, for the first time, show how benzene affect cardiac function in patients with progressing heart failure and
provide mechanistic insight into this process.

## Key facts

- **NIH application ID:** 10528089
- **Project number:** 1R21ES033334-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Igor N. Zelko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,750
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10528089

## Citation

> US National Institutes of Health, RePORTER application 10528089, Benzene Exposure and Heart Failure (1R21ES033334-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10528089. Licensed CC0.

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