# Role of Extracellular MicroRNAs in Myocardial Ischemia-Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $12,167

## Abstract

Project Summary
Heart diseases including ischemic myocardial infarction (MI) continue to be the leading cause of mortality in the
U.S. While reperfusion therapy such as percutaneous coronary intervention remains the most effective strategy
to limit infarct size and preserve cardiac function, reperfusion itself can cause lethal injury to myocardium. In
response to ischemia-reperfusion (I/R), myocardium releases various danger molecules that are proven to be
harmful to the heart. We have recently identified that cellular RNAs including many microRNAs (miRNAs) are
released from the heart during I/R and that extracellular RNA contributes to myocardial inflammation and injury.
Our preliminary investigations demonstrate that RNA isolated from the heart or single-stranded miRNA mimics
(miR-34, -122, -133a, -142, 146a, -208a) induce a robust cytokine response in cardiomyocytes, neutrophils, and
macrophages. Using genetic deletion models and pharmacological inhibitors, we demonstrate, in cell-based
assays, that cardiac RNAs or microRNA mimics induce cytokine production specifically through the innate
immune Toll-like receptor 7 (TLR7) signaling. The over goals of this proposal are to determine the role of
extracellular miRNAs in myocardial I/R injury and explore the underlying molecular mechanisms.
The proposal is based on the following three hypotheses: 1) that miRNAs are released from injured myocardium
during I/R and play a role in myocardial inflammation and injury, 2) that miRNAs act through TLR7 signaling
in cardiomyocytes and neutrophils, 3) that pharmacological inhibition of miRNAs and TLR7 signaling after
ischemic insult will offer cardio-protection against I/R injury. In Specific Aim 1, we will determine the
contribution of extracellular miRNAs to myocardial inflammation and injury during I/R. In Specific Aim 2, we
will test the role of TLR7 signaling in miRNA-mediated myocardial inflammation and injury in I/R. In Specific
Aim 3, we will explore the miRNA-TLR7 signaling as a potential therapeutic target for the treatment of
myocardial I/R injury. The proposed studies address a unique and novel function of extracellular miRNAs in
myocardial inflammation and injury, with significant implications in pathogenesis and treatment of ischemic
myocardial infarction.

## Key facts

- **NIH application ID:** 10142956
- **Project number:** 3R01GM117233-04S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** WEI CHAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $12,167
- **Award type:** 3
- **Project period:** 2016-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142956

## Citation

> US National Institutes of Health, RePORTER application 10142956, Role of Extracellular MicroRNAs in Myocardial Ischemia-Reperfusion Injury (3R01GM117233-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142956. Licensed CC0.

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