# Cardioprotective Effect of Growth Hormone Releasing Hormone

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $669,004

## Abstract

Project Summary/Abstract
Despite therapeutic advances, no current treatment fully reverses impaired heart function. Heart failure often
develops in individuals with coronary artery disease; high blood pressure or have suffered a myocardial 
infarction. Heart failure can develop at any age, but increases in prevalence with age. Moreover, individuals of 
advanced age also develop a syndrome of heart failure with preserved ejection fraction (HFpEF). Experimental
models of aging as well as human studies suggest that endogenous repair capabilities become depleted with
age. Therefore, novel interventions that preserve cardiac homeostasis are essential to reduce heart failure 
associated morbidity and mortality. Our novel and potent family of synthetic peptide analogues of Growth 
Hormone Releasing Hormone (GHRH) receptor agonists (GHRH-As) produce a comprehensive repair program in
two models of heart failure associated with ischemic heart disease. Treatment with GHRH-A improved cardiac
function and attenuated remodeling in both acute and chronic models of ischemic injury, and improved 
peripheral vascular function. These effects are mediated by direct activation of GHRH receptor signaling, promoting
endogenous cell survival and repair mechanisms. However, the cellular targets and mechanisms involved 
remain to be elucidated. The long-term goal of this proposal is to identify the mechanisms underlying GHRH-
mediated cardiac protection and apply GHRH-targeted therapeutics to prevent HFpEF. We propose a 
combination of in vivo and ex vivo approaches to test the central hypothesis that activation of GHRHR signaling 
restores cardiac structure and function in HFpEF by promoting cardiomyocyte proliferation and reducing fibrosis
and apoptosis. The specific aims of this grant are to test the hypotheses that 1) GHRH Receptor signaling 
regulates cardiomyocyte function; 2) GHRH-A therapy prevents cardiovascular changes and/or restores 
cardiovascular function in Ang II-induced mouse models of HFpEF; and 3) GHRH-As prevent and/or reverse HFpEF
in a porcine model of chronic kidney disease. Together this series of aims will provide novel insights into the
mechanisms by which GHRH-As are cardioprotective and to the development of novel and effective 
therapeutic approaches tailored to improve cardiac performance in patients with HFpEF and other cardiovascular 
diseases.

## Key facts

- **NIH application ID:** 9853831
- **Project number:** 5R01HL107110-09
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joshua M Hare
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $669,004
- **Award type:** 5
- **Project period:** 2011-01-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853831

## Citation

> US National Institutes of Health, RePORTER application 9853831, Cardioprotective Effect of Growth Hormone Releasing Hormone (5R01HL107110-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853831. Licensed CC0.

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