# Adenine metabolism in cardiac repair

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $742,320

## Abstract

PROJECT SUMMARY/ABSTRACT
The mammalian heart does not robustly regenerate after myocardial infarction and heals via a fibrotic repair
response. Scar tissue is non-contractile, increases the hemodynamic burden on the remaining cardiac muscle
and over time adverse cardiac remodeling occurs leading to ventricular dilatation and development of heart
failure. Understanding mechanisms of ventricular remodeling to redirect the cardiac injury response from a
fibrotic to a reparative one remains one of the broad therapeutic goals in cardiovascular medicine. We have
recently identified extracellular nucleotide metabolism as a novel target for cardiac remodeling after ischemic
cardiac injury. We demonstrated that after cardiac injury, the ectonucleotidase ENPP1 is upregulated and
hydrolyzes extracellular ATP into AMP. Increased AMP was converted into adenine and extracellular adenine
initiated a pro-inflammatory and pro-apoptotic cascade that caused cell death by disrupting NAD and pyrimidine
biosynthesis in non-myocytes and myocytes. However the mechanisms of adenine generation and transport
across the cell membrane, molecular and biochemical mechanisms of downstream effects on NAD and
pyrimidine biosynthesis and whether the ENPP1/AMP/Adenine axis can be targeted for therapeutic gain to
attenuate post infarct cardiac remodeling are unknown. In this proposal, we form a multi-disciplinary team
comprising experts in cardiac physiology, metabolomics, computational biology, and finally population genetics
to investigate the role of adenine metabolism in cardiac remodeling, identify its relevance as a potential
therapeutic target and its association with human cardiomyopathy.

## Key facts

- **NIH application ID:** 10975873
- **Project number:** 1R01HL171307-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Arjun Deb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $742,320
- **Award type:** 1
- **Project period:** 2024-07-25 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975873

## Citation

> US National Institutes of Health, RePORTER application 10975873, Adenine metabolism in cardiac repair (1R01HL171307-01A1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10975873. Licensed CC0.

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