Document Detail


Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction.
MedLine Citation:
PMID:  20133784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rosemeire M Kanashiro-Takeuchi; Konstantinos Tziomalos; Lauro M Takeuchi; Adriana V Treuer; Guillaume Lamirault; Raul Dulce; Michael Hurtado; Yun Song; Norman L Block; Ferenc Rick; Anna Klukovits; Qinghua Hu; Jozsef L Varga; Andrew V Schally; Joshua M Hare
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-01-21
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-10     Completed Date:  2010-05-07     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2604-9     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Medicine, Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Body Weight / drug effects
Cardiotonic Agents / pharmacology*
Echocardiography
Female
Growth Hormone / blood,  genetics,  pharmacology*
Growth Hormone-Releasing Hormone / agonists*,  analogs & derivatives,  metabolism,  pharmacology
Heart / drug effects,  physiopathology
Hemodynamics / drug effects
Immunohistochemistry
Insulin-Like Growth Factor I / metabolism
Myocardial Infarction / pathology,  prevention & control*
Myocardium / metabolism,  pathology
Organ Size / drug effects
Random Allocation
Rats
Rats, Inbred F344
Receptors, Neuropeptide / metabolism
Receptors, Pituitary Hormone-Regulating Hormone / metabolism
Recombinant Proteins / pharmacology
Grant Support
ID/Acronym/Agency:
R01-AG025017/AG/NIA NIH HHS; R01-HL084275/HL/NHLBI NIH HHS; R01-HL094848/HL/NHLBI NIH HHS; R01-HL65455/HL/NHLBI NIH HHS; U54-HL081028/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/JI-38; 0/Receptors, Neuropeptide; 0/Receptors, Pituitary Hormone-Regulating Hormone; 0/Recombinant Proteins; 0/somatotropin releasing hormone receptor; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone; 9034-39-3/Growth Hormone-Releasing Hormone
Comments/Corrections

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