New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor

Authors

Rosemeire M. Kanashiro-Takeuchi, University of Miami
Luca Szalontay, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education
Andrew V. Schally, University of Miami; Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education
Lauro M. Takeuchi, University of Miami
Petra Popovics, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education; University of Miami
Miklos Jaszberenyi, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education; University of Miami
Irving Vidaurre, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education
Marta Zarandi, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education
Ren-Zhi Cai, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education; University of Miami
Norman L. Block, University of Miami; Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education6Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida, United States of America
Joshua M. Hare, University of Miami
Ferenc G. Rick, Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education; Herbert Wertheim College of Medicine, Florida International UniversityFollow

Date of this Version

3-13-2011

Document Type

Article

Abstract

Background We previously showed that growth hormone-releasing hormone (GHRH) agonists are cardioprotective following myocardial infarction (MI). Here, our aim was to evaluate the in vitro and in vivo activities of highly potent new GHRH agonists, and elucidate their mechanisms of action in promoting cardiac repair. Methods and Results H9c2 cells were cultured in serum-free medium, mimicking nutritional deprivation. GHRH agonists decreased calcium influx and significantly improved cell survival. Rats with cardiac infarction were treated with GHRH agonists or placebo for four weeks. MI size was reduced by selected GHRH agonists (JI-38, MR-356, MR-409); this accompanied an increased number of cardiac c-kit+ cells, cellular mitotic divisions, and vascular density. One week post-MI, MR-409 significantly reduced plasma levels of IL-2, IL-6, IL-10 and TNF-? compared to placebo. Gene expression studies revealed favorable outcomes of MR-409 treatment partially result from inhibitory activity on pro-apoptotic molecules and pro-fibrotic systems, and by elevation of bone morphogenetic proteins. Conclusions Treatment with GHRH agonists appears to reduce the inflammatory responses post-MI and may consequently improve mechanisms of healing and cardiac remod eling by regulating pathways involved in fibrosis, apoptosis and cardiac repair. Patients with cardiac dysfunction could benefit from treatment with novel GHRH agonists.

Originally Published In

Oncotarget

PMID

25797248

DOI

10.18632/oncotarget.3303

Recommended Citation

Kanashiro-Takeuchi, Rosemeire M.; Szalontay, Luca; Schally, Andrew V.; Takeuchi, Lauro M.; Popovics, Petra; Jaszberenyi, Miklos; Vidaurre, Irving; Zarandi, Marta; Cai, Ren-Zhi; Block, Norman L.; Hare, Joshua M.; and Rick, Ferenc G., "New therapeutic approach to heart failure due to myocardial infarction based on targeting growth hormone-releasing hormone receptor" (2011). All Faculty. 87.
https://digitalcommons.fiu.edu/all_faculty/87

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.