# Investigating the role of SPRR1A in border zone cardiomyocytes during neonatal cardiac repair

> **NIH NIH F32** · UNIVERSITY OF ROCHESTER · 2024 · $74,284

## Abstract

PROJECT SUMMARY/ABSTRACT
Myocardial infarction (MI) causes localized cardiomyocyte (CM) death which predisposes the adult mammalian
heart to persistent fibrosis and subsequent complications such as heart failure. Border zone (BZ) CMs are a
phenotypically distinct population of cells adjacent to the ischemic region, and their response may impact the
course of heart recovery. Adult BZ CMs become hypocontractile and may be susceptible to continued cell death,
which can lead to scar expansion and exacerbate pathologic remodeling. In contrast, neonatal BZ CMs may
activate programs promoting cell survival, dedifferentiation, and proliferation that can contribute to scarless heart
repair via cardiac regeneration. Therefore, it is imperative to study how BZ CMs respond under different
conditions, as this will improve our understanding of regenerative versus non-regenerative cardiac repair.
Neonatal mouse CMs retain some proliferative capacity through the first week of life, making the neonatal heart
an excellent model to study the differences between BZ CM phenotypes. Using RNA-Sequencing and spatial
transcriptomics, we identified that small proline-rich protein 1A (Sprr1a) is transiently upregulated following
cardiac insult and is predominantly expressed in BZ CMs. To investigate BZ CM function, we made a knock-
in/knockout mouse by replacing the Sprr1a locus with a GFP expression cassette (Sprr1aGFP). Importantly, we
verified that GFP recapitulates endogenous SPRR1A expression after cardiac insult. The aims of this proposal
are to determine the role of Sprr1a during cardiac injury and characterize the BZ CM response to cardiac insult
in regenerative versus non-regenerative cardiac repair. Aim 1 will investigate how Sprr1a deletion impacts
neonatal heart regeneration in response to cryoinjury and/or apical resection. Aim 2 will explore how SPRR1A
may regulate BZ CM survival via predicted interactions with cIAP1/2. Aim 3 will characterize the transcriptomic
profile of GFP+ BZ CMs isolated from hearts injured within the proliferative window (P1) versus post-mitotic
stage (P7) in control and SPRR1A KO hearts. These findings will characterize the phenotypic response of BZ
CMs in regenerative versus non-regenerative cardiac repair and define the role of Sprr1a in this process. The
discovery of additional markers within this sub-population will be beneficial for translational research as this may
facilitate the design of targeted therapies to enhance CM cell survival or proliferation post-MI.

## Key facts

- **NIH application ID:** 10994201
- **Project number:** 1F32HL175913-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Daniel Anthony Zuppo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994201

## Citation

> US National Institutes of Health, RePORTER application 10994201, Investigating the role of SPRR1A in border zone cardiomyocytes during neonatal cardiac repair (1F32HL175913-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10994201. Licensed CC0.

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