Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure.

Proceedings of the National Academy of Sciences of the United States of America
Iacopo GesmundoRiccarda Granata

Abstract

It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gαs and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from tran...Continue Reading

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Citations

Feb 7, 2018·Journal of Cardiovascular Development and Disease·Marion LaudetteMartina Schmidt
Oct 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Andrew V SchallyXianyang Zhang
Jan 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Tania VillanovaRiccarda Granata
May 12, 2020·Frontiers in Physiology·Sebastian MartewiczNicola Elvassore
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Angela C RiegerJoshua M Hare
Apr 1, 2021·Acta Pharmacologica Sinica·Jie HuangHai-Yan Chen
Nov 30, 2021·Rejuvenation Research·Brian P HanleyGeorge Church

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Methods Mentioned

BETA
PCR
enzymatic dissociation

Software Mentioned

ImageJ

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