# Asporin, an extracellular protein, regulates cardiac remodeling

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2024 · $417,500

## Abstract

Project Summary
Extracellular matrix (ECM) is critical during cardiac remodeling in altering the cell’s response. Recently, class I
small leucine rich proteoglycans (SLRPs) showed enormous impact on the heart’s function during ischemic injury
or cardiac remodeling. Adverse cardiac remodeling stimulates fibrotic scar deposition due to increased TGFβ
activity on fibroblasts. In the last decade, a non-conventional class I SLRP protein, asporin (ASPN), has been
shown to play a role in regulating TGFβ signaling and cell viability in cancer and osteoporosis. The biological
impact of ASPN in regulating TGFβ and cell viability in heart is unknown. Our long-term goal is to dissect the
detailed mechanisms regulating ASPN activity and its impact on fibroblasts and cardiomyocytes, particularly in
the setting of cardiac remodeling. These discoveries will facilitate design of effective ASPN-based therapies for
heart failure. The objective of this grant is to characterize the role of ASPN in fibrosis and cardiomyocyte cell
viability. Our central hypothesis is that ASPN is released by fibroblasts during cardiac stress and inhibits TGFβ
signaling to reduce fibrosis during cardiac remodeling. Further, released ASPN acts on cardiomyocytes to
upregulate autophagy and prevent cell death. Our rationale is that identification of the mechanisms to stimulate
ASPN-protective effects in cardiac remodeling will offer new therapeutic opportunities. This project will further
test therapeutic peptide delivery as well as AAV9-mediated delivery of ASPN gene for efficacy in mitigating
reperfusion injury and cardiac remodeling. Our specific aims will test the following hypotheses: (Aim 1) ASPN
inhibits fibrosis to maintain cardiac function and prevents adverse cardiac remodeling; (Aim 2) ASPN induces
autophagy in cardiomyocytes; (Aim 3) ASPN regulates cardiomyocyte cell death in the setting of ischemia-
reperfusion injury. Upon conclusion, we will better understand the role of novel role of ASPN in inhibiting fibrosis
and activating autophagy for beneficial cardiac remodeling. This contribution is significant since it will establish
the several pathways targeted by ASPN from ECM to fibroblasts and cardiomyocytes. Furthermore, current
therapies, while promising in limiting ischemic injury, fail to address the key issue of adverse cardiac remodeling
in heart failure patients. The proposed research is innovative as we will investigate the effects of ASPN in
regulating fibrosis and cardiomyocyte cell death, an unexamined process to date. Insight into the mechanisms
of ASPN activity will pave the way for ASPN-based therapies to benefit cardiac remodeling.

## Key facts

- **NIH application ID:** 10862644
- **Project number:** 5R01HL155553-04
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Sarah J Parker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $417,500
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862644

## Citation

> US National Institutes of Health, RePORTER application 10862644, Asporin, an extracellular protein, regulates cardiac remodeling (5R01HL155553-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862644. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*