# The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation

> **NIH NIH F30** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $31,851

## Abstract

PROJECT SUMMARY/ABSTRACT
A common feature of heart failure (HF) is excessive extracellular matrix deposition by a specialized and
differentiated fibroblast population, known as myofibroblasts, in response to cardiac injury. While myofibroblasts
help to maintain the structural integrity of the injured heart and prevent ventricular wall rupture, persistence of
myofibroblasts results in excessive fibrosis and subsequent cardiac decompensation. Therefore, identifying
molecular mechanisms of myofibroblast differentiation in cardiac fibrosis could yield novel clinical targets to delay
or reverse the development of HF. Recent evidence suggests metabolism may drive cellular differentiation
through the modulation of epigenetic-modifying enzymes that enhance or silence genes associated with cellular
differentiation. Altered metabolism changes the concentration of metabolites that act as substrates for
epigenetically modifying enzymes, such as the changing levels of acetyl-CoA that alter the activity of histone
acetyltransferases (HAT). Our preliminary data indicate that increased glycolytic rate is a key feature driving
myofibroblast differentiation. We identified metabolic regulation of histone demethylation as a feature of
myofibroblast differentiation and we now turn our sights to histone acetylation as an epigenetic modification
permissive of myofibroblast gene expression. This proposal hypothesizes that increased acetyl-CoA
biosynthesis is necessary for histone lysine acetylation by HATs during differentiation for the transcriptional
activation of the myofibroblast gene program. This study seeks to identify novel therapeutic targets to mitigate
the consequences of fibrosis in HF.

## Key facts

- **NIH application ID:** 9990983
- **Project number:** 1F30HL152564-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Michael Lazaropoulos
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,851
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990983

## Citation

> US National Institutes of Health, RePORTER application 9990983, The Role of Acetyl-CoA Metabolism in Epigenetic Regulation of Myofibroblast Differentiation (1F30HL152564-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990983. Licensed CC0.

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