# IGF-2R is a new therapeutic target for cardiac ischemia-reperfusion injury

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2021 · $411,747

## Abstract

Project Summary/abstract
Surgical percutaneous coronary intervention is an effective reperfusion treatment for reducing acute
myocardial ischemic injury and limiting infarct size. However, the process of reperfusion can itself
induce cardiac cell damage (known as ischemia-reperfusion injury). The search for a therapeutic target
that can salvage ischemic cardiac myocytes and prevent cell death from ischemia-reperfusion injury
remains a daunting challenge. Insulin-like growth factor 2 receptor (IGF2R) exerts multiple functions
and has been implicated in cardiovascular disease. Our preliminary experiments showed that the
translocation of IGF2R to the plasma membrane was increased in response to ischemia-reperfusion
injury, while cell death was attenuated by inhibition of IGF2R. In order to further investigate IGF2R as a
new, effective target for cardioprotection, we propose three Specific Aims to define the pathological role
of IGF2R in myocardial ischemia-reperfusion injury and to provide proof-of-concept for applications of
an IGF2R antagonist in preclinical studies. Aim 1: Experiments are designed to reveal the molecular
mechanism of IGF2R redistribution in cardiomyocytes after ischemia-reperfusion injury. Interaction
between trafficking proteins and IGF2R will be investigated in this study. Aim-2: Experiments are
designed to assess cell signaling transduced by IGF2R in cardiomyocytes. The expression of IGF2R
will be modified using inducible CRISPR-based approaches to determine whether IGF2R acts as a
critical receptor mediating multiple cell death pathways (such as apoptosis and pyroptosis) in response
to ischemia-reperfusion injury. Aim-3: The therapeutic effects of an IGF2R aptamer (antagonist) will be
evaluated in mouse and porcine studies. Transgenic mice will be used to determine whether the
mechanism of IGF2R inhibition is dependent on other insulin-like growth factor receptors. The safety of
using an IGF2R aptamer will be tested in porcine models. In conclusion, the experiments outlined in this
proposal are designed to establish a new paradigm for inhibition of IGF2R using an aptamer, and will
provide a new cardioprotective strategy to reduce ischemia-reperfusion injury during heart surgeries.

## Key facts

- **NIH application ID:** 10134115
- **Project number:** 5R01HL143490-03
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Yigang Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,747
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134115

## Citation

> US National Institutes of Health, RePORTER application 10134115, IGF-2R is a new therapeutic target for cardiac ischemia-reperfusion injury (5R01HL143490-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10134115. Licensed CC0.

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