# Relaxin Signaling in Post-MI Cardiac Inflammation, Adverse Remodeling and Failure

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $388,125

## Abstract

Project Summary
The peptide hormone relaxin has traditionally been linked to the maternal adaptation of the cardiovascular
system during the first trimester of pregnancy. By activating several molecular signaling events, relaxin has
been proposed as a pleiotropic and cardioprotective hormone. Recent innovative studies by the PI and others
have demonstrated that relaxin promotes vasodilatation and angiogenesis; ameliorates ischemia/reperfusion
(I/R) injury, regulates extracellular matrix turnover and remodeling following acute myocardial infarction (AMI),
suppresses arrhythmias post MI and reverses fibrosis. More recent studies from the PI’s laboratory
demonstrated the infarct-sparing benefits of reperfusion therapy with relaxin against I/R injury as well as its role
in suppressing the NLRP3 inflammasome. The purpose of this application is to investigate and characterize the
role of relaxin receptor 1 (RXFP1) and a novel small molecule allosteric agonist (ML290) for prevention and
treatment of ischemic cardiomyopathy and inflammasome-mediated adverse remodeling and heart failure. We
will test the following hypotheses: 1) To investigate the protective effects of the small molecule ML290 on
prevention of adverse remodeling post MI and mitigation of ischemic HF. We will study the impact of
reperfusion therapy with ML290 on LV scar size, function and remodeling up to 8 weeks post MI. 2) To
determine the chronic anti-inflammatory effect of RXFP1 signaling through suppression of NLRP3-
inflammasome and the evolution of ischemic cardiomyopathy. 3) To study the impact of gain-of-
function of cardiac RXFP1 following I/R injury and its role in attenuating adverse remodeling and
progression to HF. These studies will be the first to demonstrate the protective effects of RXFP1
activation/overexpression 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 RXFP1 signaling as a
potent therapeutic target for AMI and ischemic heart failure.

## Key facts

- **NIH application ID:** 9947996
- **Project number:** 5R01HL142281-03
- **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:** $388,125
- **Award type:** 5
- **Project period:** 2018-07-15 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947996

## Citation

> US National Institutes of Health, RePORTER application 9947996, Relaxin Signaling in Post-MI Cardiac Inflammation, Adverse Remodeling and Failure (5R01HL142281-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9947996. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*