# Targeted membrane integrity in cardiac ischemia and reperfusion

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $632,339

## Abstract

Abstract
The health relevance of this proposal is outstanding due to our focus on the clinically significant problem of
myocardial ischemia/reperfusion injury (I/R), and due to our experimental emphasis on underlying mechanisms
and potential therapies. Myocardial I/R injury causes millions of human deaths per year resulting from severe
cardiac myocyte dysfunction and myocyte death, for which there is no cure or highly effective treatment. This
proposal features a sound scientific premise and substantial preliminary data indicating the critical role that
cardiac muscle membrane stabilization has in preserving cardiac tissue viability and performance in I/R. The
scientific premise guiding this proposal is that protecting cardiac muscle cell membrane integrity in I/R is
required to maintain viable myocardial tissue in I/R, and that this is essential for long-term successful
outcomes. We focus on synthetic copolymers as cell extrinsic cardiac muscle membrane stabilizers.
Copolymer-based membrane stabilizers are amphiphilic long-chain macromolecular copolymers that interact
with and protect the cardiac sarcolemma during stress. The guiding hypothesis is that synthetic copolymers
interface directly with the damaged cardiac sarcolemma to confer stabilization. Aim 1 focuses on state-of-the-
art copolymer-membrane interface structure-function investigations. In complement, Aim 2 investigates cell
extrinsic synthetic muscle membrane stabilizers and the mechanism of their complementation with cell intrinsic
myocardial cell membrane stabilization and repair pathways to preserve viable cardiac tissue and enhance
heart performance during the critical recovery phase following I/R in vivo. To advance these Aims, we leverage
an outstanding group of highly collaborative investigators spanning expertise in molecular and integrative
physiology, biochemistry, chemical engineering, and clinical cardiology. Our unique group is highly interactive
and interdependent. Together, we are ideally positioned to propel discovery in I/R mechanisms and
experimental therapeutics. Impact potential is outstanding by virtue of the mechanistic insights obtained that
will ultimately guide the therapeutic development of membrane stabilizers for I/R patients.

## Key facts

- **NIH application ID:** 9976559
- **Project number:** 5R01HL122323-06
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JOSEPH Mark METZGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $632,339
- **Award type:** 5
- **Project period:** 2014-12-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976559

## Citation

> US National Institutes of Health, RePORTER application 9976559, Targeted membrane integrity in cardiac ischemia and reperfusion (5R01HL122323-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976559. Licensed CC0.

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