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

Authors: Kanashiro-Takeuchi, RM  Tziomalos, K  Takeuchi, LM  Treuer, AV  Lamirault, G  Dulce, R  Hurtado, M  Song, Y  Block, NL  Rick, F  Klukovits, A  Hu, Q  Varga, JL  Schally, AV  Hare, JM 
Citation: Kanashiro-Takeuchi RM, etal., Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2604-9. Epub 2010 Jan 21.
Pubmed: (View Article at PubMed) PMID:20133784
DOI: Full-text: DOI:10.1073/pnas.0914138107

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 microg/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.


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CRRD Object Information
CRRD ID: 2325186
Created: 2010-05-21
Species: All species
Last Modified: 2010-05-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.