# Endothelial Mechanism In RIPC

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2020 · $483,908

## Abstract

Remote ischemic preconditioning (RIPC) is a clinically effective and non-invasive
ischemia-reperfusion (I/R) of a remote organ that provides significant protection against
more acute I/R. However, the specific protective factor released by RIPC or the
mechanism of RIPC-mediated protection remains elusive so far. Further, the
understanding by which the RIPC released factor confers protection to the heart in I/R
remains unclear. We have identified Neuregulin (Nrg1β) as one of the RIPC factors that
is required for conferring protection to the myocardium in I/R. Our proposed studies will
uncover and endothelial mechanism that RIPC-mediated Nrg1β utilizes to provide
protection in I/R injury. We will test the hypothesis that RIPC-mediated release of Nrg1β
protects coronary endothelial dysfunction by interacting with its receptor ErbB2
expressed in endothelial cells, and this endothelial Nrg1β-ErbB2 interaction induces
survival signaling resulting in protection against myocardial ischemia-reperfusion injury.
Our hypothesis is novel and intriguing as endothelial Nrg1β is believed to interact with
ErbB2 expressed on cardiomyocytes. Our studies will investigate for the first time the
role of Nrg1β-ErbB2 in the coronary endothelium that elicits survival pathway to protect
myocardium in I/R. In our aim 1, we will determine the mechanism of RIPC mediated
release of Nrg1β that is required for protection against MI; Aim 2) we will determine
mitochondrial redox mechanism induced due to protection ErbB2 degradation and its
role in protection against coronary endothelial dysfunction due to I/R; Aim 3) the role of
RIPC –mediated rescue of ErbB2 and resultant decrease in ROS in protection against
endothelial dysfunction, myocardial I/R will be determined. We will use novel mouse
model with specific deletion of ErbB2 in the endothelial cells to understand the specific
role of endothelial ErbB2 in RIPC-dependent protection of myocardium in I/R. We will
use state-of-the art experimental methodology such as proximity ligation assays,
pressure and wire myography, echocardiography and molecular and biochemical
approaches to delineate the precise role of RIPC-mediated Nrg1β in protection against
MI.

## Key facts

- **NIH application ID:** 9900065
- **Project number:** 5R01HL144610-02
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** KUMUDA C DAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $483,908
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900065

## Citation

> US National Institutes of Health, RePORTER application 9900065, Endothelial Mechanism In RIPC (5R01HL144610-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9900065. Licensed CC0.

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