Journal Article

Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction

Kanashiro-Takeuchi, Rosemeire M, Dulce, Raul, Klukovits, Anna, Takeuchi, Lauro M, Varga, Jozsef L, Tziomalos, Konstantinos, Hu, Qinghua, Lamirault, Guillaume, Hurtado, Michael, Rick, Ferenc, Hare, Joshua M, Song, Yun, Block, Norman L, Treuer, Adriana V, Schally, Andrew V

2010

Overview

Whether the growth hormone (GH)/insulin-like growth factor 1(IGF-1) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth hormone-releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-1 independent fashion. After experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4-week period, either placebo (n = 14), rat recombinant GH (n = 8) or JI-38 (n = 8; 50 μg/kg per day), a potent GHRH agonist. JI-38 did not elevate serum levels of GH or IGF-1, but it markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, and circulating GH and IGF-1, but it did not offset the decline in cardiac structure and function. Whereas both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased antiapoptotic gene expression. The receptor for GHRH was detectable on myocytes, supporting direct activation of cardiac signal transduction. Collectively, these findings demonstrate that within the heart, GHRH agonists can activate cardiac repair after MI, suggesting the existence of a potential signaling pathway based on GHRH in the heart. The phenotypic profile of the response to a potent GHRH agonist has therapeutic implications.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: agonists / Animals / Apoptosis / Biological Sciences / blood serum / Blotting, Western / Body weight / Body Weight - drug effects / cardioprotective effect / Cardiotonic Agents - pharmacology / Cell growth / cell proliferation / Echocardiography / Female / Gene expression / Growth Hormone - blood / Growth Hormone - genetics / Growth Hormone - pharmacology / Growth Hormone-Releasing Hormone - agonists / Growth Hormone-Releasing Hormone - analogs & derivatives / Growth Hormone-Releasing Hormone - metabolism / Growth Hormone-Releasing Hormone - pharmacology / Growth hormones / Heart / Heart - drug effects / Heart - physiopathology / Heart attacks / Hemodynamics - drug effects / Hormones / Immunohistochemistry / insulin-like growth factor I / Insulin-Like Growth Factor I - metabolism / Mast cells / Myocardial infarction / Myocardial Infarction - pathology / Myocardial Infarction - prevention & control / Myocardium / Myocardium - metabolism / Myocardium - pathology / myocytes / Organ Size - drug effects / phenotype / Placebos / Random Allocation / Rats / Rats, Inbred F344 / Receptors / Receptors, Neuropeptide - metabolism / Receptors, Pituitary Hormone-Regulating Hormone - metabolism / Recombinant Proteins - pharmacology / Renovations / Rodents / signal transduction / somatoliberin / somatotropin / Stem cells / T cell receptors