# Mechanisms of eosinophil-associated heart disease

> **NIH NIH R56** · UNIVERSITY OF CINCINNATI · 2021 · $422,982

## Abstract

PROJECT SUMMARY
Cardiac complications occur in 20-60% of patients with peripheral blood hypereosinophilia irrespective
of the cause—hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis
(EGPA, formerly known as Churg-Strauss syndrome), drug reaction, or parasitic infection. Importantly,
heart disease is the main cause of morbidity and mortality in this diverse group of patients. There is a
paucity of models that adequately replicate cardiac disease in hypereosinophilia, which hinders
mechanistic research that would identify therapeutic targets and advance clinical practice. To address
this gap, we recently developed a mouse model of eosinophilic myocarditis that recapitulates many of
the features of the disease including eosinophilia with heart involvement leading to early death. Our
long-term goal is to understand the cellular and molecular mechanisms of eosinophil-mediated tissue
damage. The objective of this grant is to use this mouse model to address critical questions regarding
the pathophysiology of eosinophil-mediated cardiac disease. Our central hypothesis is that eosinophils
and specific types of eosinophil cell death have a pathogenic role in eosinophilic myocarditis. We
propose two specific aims: 1) define the role of eosinophils and their regulated necrosis in eosinophilic
myocarditis; and 2) test for evidence of regulated necrosis and anti-eosinophil autoantibodies in
patients with eosinophil-associated diseases. These contributions are significant because heart
disease is the major cause of morbidity and mortality in patients with hypereosinophilic diseases; the
studies in this grant application will enable directly testing mechanistic hypotheses in a model of
eosinophilic myocarditis with features reminiscent of those seen in patients with heart disease as a
consequence of hypereosinophilia. This project is innovative because it proposes to test innovative
hypotheses, including the role of a recently described mode of biochemically regulated and thus
targetable eosinophil cell death. Furthermore, the approach is innovative in that we use a new mouse
model of spontaneous eosinophilic myocarditis. Understanding more about cardiac disease in a
hypereosinophilic setting will provide mechanistic insights that may be generalizable to other conditions
of eosinophil-associated heart disease.

## Key facts

- **NIH application ID:** 10117454
- **Project number:** 1R56HL147898-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** NIVES Zimmermann
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $422,982
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117454

## Citation

> US National Institutes of Health, RePORTER application 10117454, Mechanisms of eosinophil-associated heart disease (1R56HL147898-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10117454. Licensed CC0.

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