# Satellite Glial Cell Activation and Sympathetic Imbalance in Cardiomyopathy and Arrhythmias

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $591,829

## Abstract

PROJECT SUMMARY/ABSTRACT
Cardiac injury predisposes patients to heart failure (HF), and ventricular tachycardia/fibrillation (VT/VF).
Development of HF and VT/VF after cardiac injury is tightly linked to sympathetic neural remodeling. Although
several medications targeting cardiac sympathetic excess reduce mortality following cardiac injury, significant
shortcomings of these drugs include off-target effects, limited efficacy, and focus on downstream
consequences of neural remodeling such as excess catecholamine release, rather than preventing it upstream.
In this proposal, we build on strong preliminary data from humans, porcine, and murine models demonstrating
that satellite glial cell (SGC) activation is a central feature of chronic cardiac injury. Activated glia release
inflammatory cytokines, ATP, and other factors that modulate neuronal function. Chemogenetic upregulation of
glial calcium signaling (as observed in activated glia) increase cardiac sympathetic neuronal excitability,
synaptic efficacy, and tonic firing. Based on these novel findings, the goal of this proposal is to test the
hypothesis that satellite glial activation and enhanced glial-neuronal signaling is a primary driver of cardiac
sympathetic neuronal dysfunction, heart failure and VT/VF after cardiac injury.
 We will test our hypotheses using novel tools from a multidisciplinary team of investigators in 3 specific
aims in two murine models of cardiac injury (ischemia-reperfusion and dilated cardiomyopathy). We will test
whether following cardiac injury, satellite glial cell activation within stellate ganglia exacerbates neuronal and
cardiac remodeling (structural and functional) to promote LV dysfunction and VT/VF (Aim 1). We will
investigate the mechanisms by which cardiac injury activates SGCs in stellate ganglia after injury (Aim 2).
Finally, we will determine whether targeting glial Gq-GPCR Ca2+ signaling or Cx43-mediated glia-neuron/glial-
glial communication mitigates adverse remodeling and arrhythmogenesis following cardiac injury (Aim 3). The
results of this proposal will 1) indicate whether and how satellite glial cell activation contributes to sympathetic
imbalance after cardiac injury; and 2) determine whether targeting satellite glial cell activation offers
therapeutic potential in chronic cardiac injury.

## Key facts

- **NIH application ID:** 10416426
- **Project number:** 1R01HL162717-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Olujimi A Ajijola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $591,829
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416426

## Citation

> US National Institutes of Health, RePORTER application 10416426, Satellite Glial Cell Activation and Sympathetic Imbalance in Cardiomyopathy and Arrhythmias (1R01HL162717-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10416426. Licensed CC0.

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