# Channelopathies of Inflammation

> **NIH HL R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2026 · $606,611

## Abstract

PROJECT ABSTRACT
Obesity is associated with a higher risk for the development of malignant ventricular tachyarrhythmias (VT),
particularly under conditions of repolarization disorders and QT interval prolonging mechanisms (an
established risk factor for VT), and sometimes tragically transitions to sudden cardiac death. In obesity, excess
dietary fat in adipose tissues stimulates the release of immunomodulatory cytokines such as interleukin(IL)-6,
leading to a state of chronic inflammation in patients. In the past decade, IL-6 trans-signaling has emerged as
a powerful predictor of risk for VT. The first selective inhibitor of IL-6, olamkicept, has shown encouraging
results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6
and VT remains undiscovered. The long-term goal is to help inform the development of therapeutically novel
anti-cytokine drugs for the clinical treatment of life-threatening malignant VT. The overall objectives in this
application are to (i) elucidate the molecular mechanism(s) by which IL-6 signaling triggers dramatic and
arrhythmogenic electrical changes in vitro and (ii) determine in vivo anti-IL-6 signaling anti-arrhythmic efficacy
using a guinea pig high-fat diet-induced inflammation model. Our central hypothesis is that over-activation of
IL-6 trans-signaling triggers proarrhythmogenic changes in the rapidly activating delayed rectifier K channel
(IKr) and calcium (Ca) handling in vitro and promotes lethal VT in vivo by promoting electrical disturbances in
the ventricular myocardium. The rationale for this project is that a determination of the therapeutic potential of
IL-6 signaling inhibition and associated cellular mechanisms is likely to reveal a strong mechanistic basis
whereby new strategies to treat lethal ventricular arrhythmias in patients can be developed. The central
hypothesis will be tested by pursuing two specific aims: 1) determine anti-arrhythmic effects of IL-6 signaling
inh

## Key facts

- **NIH application ID:** 11258042
- **Project number:** 5R01HL177965-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Ademuyiwa  Aromolaran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $606,611
- **Award type:** 5
- **Project period:** 2025-01-10T00:00:00 → 2028-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11258042

## Citation

> US National Institutes of Health, RePORTER application 11258042, Channelopathies of Inflammation (5R01HL177965-02). Retrieved via AI Analytics 2026-07-17 from https://api.ai-analytics.org/grant/nih/11258042. Licensed CC0.

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