# Neurotrophins and post-infarct plasticity in cardiac sympathetic neurons

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $629,790

## Abstract

Project Summary
Coronary heart disease is the leading cause of death in the U.S., and patients who survive a coronary artery
occlusion have a high risk for cardiac arrhythmias and sudden cardiac death. Spatial heterogeneity of
sympathetic innervation is a major contributor to post-infarct arrhythmias and sudden cardiac death after
myocardial infarction (MI), and sympathetic denervation (nerve loss) predicts arrhythmia risk in human studies.
Persistent denervation is caused by chondroitin sulfate proteoglycans (CSPGs) in the scar acting on neuronal
Protein Tyrosine Phosphatase Receptor Sigma (PTPσ). Targeting PTPσ with therapeutics or removing
sulfation from CSPG side chains promotes post-MI reinnervation of the borderzone and infarct, preventing
isoproterenol-induced arrhythmias and altering the cardiac immune response. Treatments that restore
innervation shift the cardiac immune response from pro-inflammatory to reparative, but the role of reinnervation
and neurotransmission in that process remains unknown. Several lines of evidence suggest that reinnervation
regulates inflammation, and that noradrenergic transmission is involved. We will test that hypothesis in Aim 1.
Conversely, preliminary data indicate that restoring sympathetic nerves prevents isoproterenol-induced
arrhythmias even if the nerves lack norepinephrine. This surprising result suggests that another aspect of
reinnervation, aside from noradrenergic transmission, is critical for normalizing cardiac β1AR signaling and
electrophysiology after MI. We will test the hypothesis that post-MI reinnervation prevents arrhythmias by
restoring a β1AR-SAP97 (β1 adrenergic receptor-synapse associated protein 97) signaling complex in cardiac
myocytes. We hypothesize that post-MI sympathetic reinnervation regulates cardiac inflammation and
electrophysiology via distinct mechanisms, and we have assembled an outstanding team of experts and
innovative experimental tools to identify the mechanisms involved.

## Key facts

- **NIH application ID:** 10879716
- **Project number:** 2R01HL093056-14A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** BETH A HABECKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $629,790
- **Award type:** 2
- **Project period:** 2009-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879716

## Citation

> US National Institutes of Health, RePORTER application 10879716, Neurotrophins and post-infarct plasticity in cardiac sympathetic neurons (2R01HL093056-14A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10879716. Licensed CC0.

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