TY - JOUR
T1 - Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction
AU - Kanashiro-Takeuchi, Rosemeire M.
AU - Tziomalos, Konstantinos
AU - Takeuchi, Lauro M.
AU - Treuer, Adriana V.
AU - Lamirault, Guillaume
AU - Dulce, Raul
AU - Hurtado, Michael
AU - Song, Yun
AU - Block, Norman L.
AU - Rick, Ferenc
AU - Klukovits, Anna
AU - Hu, Qinghua
AU - Varga, Jozsef L.
AU - Schally, Andrew V.
AU - Hare, Joshua M.
PY - 2010/2/9
Y1 - 2010/2/9
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cardiac stem cells
KW - Heart failure
KW - Remodeling
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U2 - 10.1073/pnas.0914138107
DO - 10.1073/pnas.0914138107
M3 - Article
C2 - 20133784
AN - SCOPUS:77249162694
SN - 0027-8424
VL - 107
SP - 2604
EP - 2609
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -