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

Rosemeire 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 Hare

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2604-2609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number6
DOIs
StatePublished - Feb 9 2010

Fingerprint

Growth Hormone-Releasing Hormone
Growth Hormone
Myocardial Infarction
Somatomedins
Muscle Cells
Signal Transduction
Placebos
Body Weight
Cell Proliferation
Gene Expression
Weights and Measures
JI-38
Wounds and Injuries
Serum

Keywords

  • Apoptosis
  • Cardiac stem cells
  • Heart failure
  • Remodeling

ASJC Scopus subject areas

  • General

Cite this

Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction. / Takeuchi, Rosemeire; Tziomalos, Konstantinos; Takeuchi, Lauro M.; Treuer, Adriana V.; Lamirault, Guillaume; Dulce, Raul; Hurtado, Michael; Song, Yun; Block, Norman L; Rick, Ferenc; Klukovits, Anna; Hu, Qinghua; Varga, Jozsef L.; Schally, Andrew V; Hare, Joshua.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 6, 09.02.2010, p. 2604-2609.

Research output: Contribution to journalArticle

Takeuchi, R, 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, J 2010, 'Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 6, pp. 2604-2609. https://doi.org/10.1073/pnas.0914138107
Takeuchi, Rosemeire ; Tziomalos, Konstantinos ; Takeuchi, Lauro M. ; Treuer, Adriana V. ; Lamirault, Guillaume ; Dulce, Raul ; Hurtado, Michael ; Song, Yun ; Block, Norman L ; Rick, Ferenc ; Klukovits, Anna ; Hu, Qinghua ; Varga, Jozsef L. ; Schally, Andrew V ; Hare, Joshua. / Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 6. pp. 2604-2609.
@article{a5f6c3312cf04870a9c7600fc0f1b4e3,
title = "Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction",
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 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.",
keywords = "Apoptosis, Cardiac stem cells, Heart failure, Remodeling",
author = "Rosemeire Takeuchi and Konstantinos Tziomalos and Takeuchi, {Lauro M.} and Treuer, {Adriana V.} and Guillaume Lamirault and Raul Dulce and Michael Hurtado and Yun Song and Block, {Norman L} and Ferenc Rick and Anna Klukovits and Qinghua Hu and Varga, {Jozsef L.} and Schally, {Andrew V} and Joshua Hare",
year = "2010",
month = "2",
day = "9",
doi = "10.1073/pnas.0914138107",
language = "English",
volume = "107",
pages = "2604--2609",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "6",

}

TY - JOUR

T1 - Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction

AU - Takeuchi, Rosemeire

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

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

UR - http://www.scopus.com/inward/record.url?scp=77249162694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77249162694&partnerID=8YFLogxK

U2 - 10.1073/pnas.0914138107

DO - 10.1073/pnas.0914138107

M3 - Article

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

SN - 0027-8424

IS - 6

ER -