# Regulation of TRAF2-Dependent Inflammatory Signaling by Small Proline Rich Protein 1A in the Myocardium

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2022 · $46,752

## Abstract

ABSTRACT:
Heart failure (HF) is a leading cause of death worldwide and defined by an inability of the heart to pump sufficient
blood throughout the body. HF can be induced by persistent conditions such as high blood pressure, or by acute
injuries such as myocardial infarction (MI). MI is characterized by the obstruction of a coronary blood vessel
resulting in ischemia. Cardiomyocytes (CMs) affected by the ischemia undergo necrosis and apoptosis. To clear
the resulting cellular debris, immune cells infiltrate the area while resident fibroblasts begin to secrete an
extracellular matrix-rich scar to maintain the structural integrity of the heart. This eloquent response is essential
to overcoming the initial injury, and exaggeration of any particular phase can have detrimental effects. While the
etiology of disease associated with high blood pressure and MI are unique, they share similar features such as
hypertrophy, inflammation, and fibrosis. To better understand the process of pathological cardiac remodeling,
we performed RNA-sequencing to identify transcriptional gene expression profiles associated with pathologic
fates. We identified a family of small proline-rich proteins (SPRRs) that are differentially regulated in disease;
Sprr1a is highly upregulated in response to inflammatory cytokines in CFs and CMs in the border zone (BZ) after
MI. Preliminary data suggests a predicted binding site between SPRR1A and tumor necrosis factor (TNF)
receptor associated factor (TRAF)2, an E3 ubiquitin ligase that acts in response to the TNF receptor at the
plasma membrane to propagate inflammatory signaling. Further investigation has led us to hypothesize that
SPRR1A is altering the ubiquitination status or proteasome function in CMs to halt pro-inflammatory signaling
and allow for the increase in inflammation-resolution pathways to occur. Separately, SPRR1A and TRAF2 may
also be playing a role in the rate of cell survival along the border of injury. Understanding the coordination of the
healing response following MI will build the basis needed for further therapeutic developments. This proposal
aims to determine the novel in vitro mechanism of action and associated in vivo complications associated with
the modulation of SPRR1A expression.

## Key facts

- **NIH application ID:** 10375803
- **Project number:** 1F31HL158037-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Kimberly Nicole Burgos Villar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-01-07 → 2024-01-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375803

## Citation

> US National Institutes of Health, RePORTER application 10375803, Regulation of TRAF2-Dependent Inflammatory Signaling by Small Proline Rich Protein 1A in the Myocardium (1F31HL158037-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10375803. Licensed CC0.

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