# Fibroblast targeting for myocardial repair

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $646,395

## Abstract

Abstract
 Heart failure (HF) continues to be a leading cause of death, disability and health
care expenditures. Coronary artery disease culminating in a myocardial infarction (MI)
remains a major cause for HF. HF secondary to MI is fundamentally due to changes in
the structure and function of the left ventricle (LV) termed LV remodeling. In pathological
remodeling such as cancer, the proliferation of an aggressive degradative cell type, the
cancer associated fibroblast emerges. The cancer associated fibroblast alters normal
tissue structure through degradation/remodeling of the extracellular matrix (ECM). In
particular, a robust expression of a proteolytic enzyme, fibroblast activation protein (FAP).
We have identified that the post-MI fibroblast contains a very similar proteolytic signature
as the cancer associated fibroblast, in terms of ECM degradation and ultimately LV
remodeling. Accordingly, we will test the guiding hypothesis that FAP induction/activation
is essential for adverse post-MI remodeling and progression to HF and that specific
localized targeting of FAP within the MI region is feasible and effective. The outcome from
these translational studies will be to establish an entirely new therapeutic direction for
myocardial recovery following MI and prevention of HF. We have established a transgenic
line of FAP conditional knockout mice which will allow for FAP silencing following MI
induction as well as following the development of HF. We have developed unique
hydrogel formulations that allow for the release of small molecule therapeutics and
protease inhibitors, which have been deployed in our pig model post-MI using a minimally
invasive approach. The deliverables from this project will be to establish a novel
therapeutic direction for the prevention as well as the treatment for HF secondary to MI
through both temporal and localized control of FAP activation. These results will move
the entire ECM field forward by establishing the role of the fibroblast in HF and open an
entirely new direction through harnessing novel molecular tools and therapeutics to target
specific cell phenotypes in this disease process.

## Key facts

- **NIH application ID:** 10809692
- **Project number:** 5R01HL167994-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** FRANCIS G SPINALE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $646,395
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809692

## Citation

> US National Institutes of Health, RePORTER application 10809692, Fibroblast targeting for myocardial repair (5R01HL167994-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10809692. Licensed CC0.

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