Language

English

Publication Date

11-5-2024

Journal

Journal of Cardiovascular Development and Disease

DOI

10.3390/jcdd11110355

PMID

39590198

PMCID

PMC11595155

PubMedCentral® Posted Date

11-5-2024

PubMedCentral® Full Text Version

Post-print

Abstract

The number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overexpression significantly increased the expression of a Pnoc gene, an endogenous ligand for the cell membrane receptor ORL1. We hypothesized that the activation of the ORL1 receptor would suppress HF in a rat ischemic heart model. Adult Sprague Dawley rats (8 weeks old, six males and six females) underwent left anterior descending coronary artery ligation. Three weeks later, normal saline or MCOPPB (ORL1 activator, 2.5 mg/kg/day) intraperitoneal injection was started, and continued 5 days a week for 3 months. Echocardiography was performed six times: pre-operative, 3 days after coronary artery ligation, pre-MCOPPB or saline injection, and 1, 2, and 3 months after saline or MCOPPB injection started. Animals were euthanized after 3 months’ follow-up and the hearts were harvested for histological analysis. The ORL1 activator, MCOPPB, significantly improved cardiac function after myocardial infarction in rats (ejection fraction, MCOPPB vs. saline at euthanasia, 67 ± 3% vs. 43 ± 2%, p < 0.001). MCOPPB also decreased fibrosis and induced angiogenesis. Thus, the ORL1 activator, MCOPPB, may be a novel treatment for preventing HF progression.

Keywords

prevention of ischemic heart failure progression, ORL1 receptor activation, MCOPPB

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.