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

Oncotarget
Rosemeire M Kanashiro-TakeuchiFerenc G Rick

Abstract

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. 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-α 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. Treatment with GHRH agonists appears to reduce the inflammatory responses post-MI and may consequently improve mechanisms of healing and cardiac remodeling by regulating pathways...Continue Reading

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Citations

Nov 9, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hippokratis Kiaris, Ioulia Chatzistamou
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Iacopo GesmundoRiccarda Granata
Oct 26, 2016·Frontiers in Endocrinology·Leonid E FridlyandLouis H Philipson
Apr 2, 2015·Journal of the American Heart Association·Luiza L BagnoJoshua M Hare
Feb 20, 2016·Journal of Endocrinological Investigation·R Granata
Oct 21, 2017·Heart Failure Reviews·Antonios RigasJohn Parissis
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Angela C RiegerJoshua M Hare

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