# Epigenomic basis of resilience to heart failure

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $234,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Epigenomic features centrally underpin cardiovascular health. Among these, DNA methylation has
emerged as a stable, but not immutable, chromatin modification that can be associated with gene expression
but yet decorates non-genic regions of the genome, influencing cellular function by means other than
transcription at the locus it occurs. In this grant we seek to determine whether these epigenomic marks can serve
to predict—prior to the development of severe complications—heart failure, and to explore the underlying
mechanisms of epigenomic resilience to cardiovascular disease. Rather than studying the disease process, we
see to understand why some individuals develop heart failure whereas others do not.
 Our preliminary work in mouse models shows that DNA methylation in the heart of mice correlates with
the severity of disease prior to the exposure to environmental stress (e.g. isoproterenol). Following up on this
initial observation, we have now characterized DNA methylomes in a panel of inbred and recombinant inbred
mouse strains, allowing us to explore the basic principles of how DNA methylation interacts with genetic variation
to influence cardiovascular resilience. We now seek to translate this phenomenon to humans, identifying multi-
locus epigenomic risk metrics for heart failure that distinguish resilient individuals from those more
susceptible to cardiovascular complications over time. These metrics will be the basis for a new class of precision
prognostic and diagnostic tools in heart failure.
 Our research team has initiated an IRB-approved clinical program to measure epigenetic factors in the
blood of patients undergoing cardiac surgery, linking these factors to clinical data through an innovative data-
mining platform that interrogates electronic medical records. As of February 2019, we have enrolled ~250
patients and performed bisulfite sequencing on 110 of them (remaining patients’ samples in process). Moving
forward, independent of this application, we continue to expand this cohort to include a representative sampling
of the adult population in the Los Angeles region. The hypothesis we will test in this grant is that DNA methylation
mechanistically underpins differential resilience to cardiac pathology and is a source of a novel class of
biomarkers for human heart failure.

## Key facts

- **NIH application ID:** 9877829
- **Project number:** 1R21HL150667-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Thomas M. Vondriska
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877829

## Citation

> US National Institutes of Health, RePORTER application 9877829, Epigenomic basis of resilience to heart failure (1R21HL150667-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9877829. Licensed CC0.

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