Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction.
Τίτλος | Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Kanashiro-Takeuchi, R. M., Tziomalos K., Takeuchi L. M., Treuer A. V., Lamirault G., Dulce R., Hurtado M., Song Y., Block N. L., Rick F., Klukovits A., Hu Q., Varga J. L., Schally A. V., & Hare J. M. |
Journal | Proc Natl Acad Sci U S A |
Volume | 107 |
Issue | 6 |
Pagination | 2604-9 |
Date Published | 2010 Feb 9 |
ISSN | 1091-6490 |
Λέξεις κλειδιά | Animals, Blotting, Western, Body Weight, Cardiotonic Agents, Echocardiography, Female, Growth Hormone, Growth Hormone-Releasing Hormone, Heart, Hemodynamics, Immunohistochemistry, Insulin-Like Growth Factor I, Myocardial Infarction, Myocardium, Organ Size, Random Allocation, Rats, Rats, Inbred F344, Receptors, Neuropeptide, Receptors, Pituitary Hormone-Regulating Hormone, Recombinant Proteins |
Abstract | 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. |
DOI | 10.1073/pnas.0914138107 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 20133784 |
PubMed Central ID | PMC2823907 |
Grant List | R01-AG025017 / AG / NIA NIH HHS / United States R01-HL084275 / HL / NHLBI NIH HHS / United States R01-HL094848 / HL / NHLBI NIH HHS / United States R01-HL65455 / HL / NHLBI NIH HHS / United States U54-HL081028 / HL / NHLBI NIH HHS / United States |