# Circular RNAs as novel mediators of cardiac repair

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $549,897

## Abstract

PROJECT SUMMARY
Cardiovascular disease is the leading cause of death and pharmacologic treatment strategies have
improved cardiovascular outcomes and survival. However, the prognoses of affected individuals remain
poor; hence, the need to elucidate underlying mechanisms and develop better therapies for
cardiovascular diseases. Our proposed studies focus on circRNA as an unexplored component of the
cardiovascular system to yield new understanding and tools for treatment of myocardial infarction. The
overarching objective of this current revised application is to reveal how circular RNAs (circRNAs), a
recently identified class of RNAs that are generated from many protein-coding genes, impact mouse
models of myocardial infarction (MI). Preliminary data generated for the current proposal shows that
modulation of a specific circRNA from the Fibronectin Type III Domain Containing 3B (FNDC3b) gene
(circFNDC3b) in ischemic myocardium can modulate cardiac repair after myocardial infarction in mice.
In particular, we found: 1) decreased circFNDC3b expression in post-MI mouse hearts and in left
ventricular tissues of ischemic cardiomyopathy patients, 2) and in endothelial cells and cardiomyocytes
in post-MI mouse hearts; 3) AAV9 mediated circFNDC3b overexpression enhances endothelial cell
angiogenesis and inhibits hypoxia-induced cardiomyoblast apoptosis in vitro, 4) and improves left
ventricular function, remodeling and neovascularization post-MI in mice; 5) circFNDC3b bind RNA
binding protein fused in sarcoma (FUS-1) in endothelial cells and cardiomyoblasts and regulate FUS-
1 levels. Our central hypothesis is that rescue of circFNDC3b promotes positive cardiac remodeling
after MI by enhancing neovascularization and improves cardiomyocyte cell survival through FUS-1
inhibition, thus improving cardiac function. This research will create a multi-modal platform for future
work, accelerating progress in this field as it relates to therapeutic targets and underlying mechanisms.
The hypotheses will be tested under the following 3 specific aims: Specific Aim 1: To determine the
physiological role of circFNDC3b on myocardial injury repair post-MI in mice. Specific Aim 2: To
elucidate the molecular mechanism by which circFNDC3b regulates cardiomyocyte cell survival and
enhances endothelial cell function. Specific Aim 3: To develop novel therapeutic strategies to
manipulate other circRNAs to promote myocardial injury repair post-MI in mice. Successful completion
of the proposed research will potentially identify circRNAs as potentially novel therapeutic targets for
ischemic myocardial repair.

## Key facts

- **NIH application ID:** 10120714
- **Project number:** 5R01HL091983-11
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Raj Kishore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,897
- **Award type:** 5
- **Project period:** 2009-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120714

## Citation

> US National Institutes of Health, RePORTER application 10120714, Circular RNAs as novel mediators of cardiac repair (5R01HL091983-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10120714. Licensed CC0.

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