# Hydrogen Sulfide for Prevention and Treatment of Ischemic Heart Failure

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $381,250

## Abstract

Project Summary
Hydrogen sulfide (H2S) is a powerful gasotransmitter, which has been shown to possess robust protective
effects against ischemia-related injuries in the heart and other organs. Recent innovative studies by the PI and
colleagues have identified regulation of endogenous levels of H2S to mediate the cardioprotective effect of
phosphodiesterase-5 inhibitor, tadalafil, as well as a potent nitric oxide (NO)-independent guanylate cyclase
activator, Cinaciguat, in the mouse heart. More recent studies from the PI's laboratory demonstrated the
infarct-sparing and anti-inflammatory benefits of exogenous H2S against ischemia/reperfusion (I/R) injury as
well as the role of cystathionine-γ-lyase-driven H2S generation in mediating the cardioprotective effects of gene
therapy with protein kinase G. The purpose of this application is to further investigate the novel mechanisms by
which H2S attenuates ischemic cardiomyopathy and inflammasome-mediated adverse remodeling in the failing
heart. We will test the following hypotheses: 1) To investigate the protective effects of H2S on prevention
of adverse remodeling post myocardial infarction (MI) and mitigation of ischemic heart failure. We will
study the impact of H2S on LV scar size, function and remodeling. 2) To determine the chronic anti-
inflammatory effect of H2S through suppression of NLRP3-inflammasome and the evolution of
ischemic cardiomyopathy. 3) To study the role of H2S in attenuation of mitochondrial damage and
propagation of inflammatory injury following MI by preserving MAVS and suppressing cofilin-2. These
studies will be the first to demonstrate the protective effects of H2S for prevention of adverse remodeling
following MI and also its potential therapeutic utility in the failing heart, possibly through attenuation of
inflammasome-mediated maladaptive signaling. This is especially novel and the results will have a tremendous
impact on further endorsing H2S as a potent therapeutic agent for ischemic heart failure. Moreover, these
studies will provide novel mechanistic information by which new synthetic pharmacological agents with
precisely controlled H2S release lead to improvement in overall cardiovascular health.

## Key facts

- **NIH application ID:** 9947998
- **Project number:** 5R01HL133167-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Fadi N Salloum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2016-07-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947998

## Citation

> US National Institutes of Health, RePORTER application 9947998, Hydrogen Sulfide for Prevention and Treatment of Ischemic Heart Failure (5R01HL133167-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9947998. Licensed CC0.

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