Division of Cardiology, Department of Medicine, Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2604-9. doi: 10.1073/pnas.0914138107. Epub 2010 Jan 21.
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.
生长激素（GH）/胰岛素样生长因子 1（IGF-1）轴是否具有心脏保护作用仍存在争议；其作用的潜在机制尚不清楚。在这里，我们通过实验性心肌梗死（MI）来检验这样一个假设，即生长激素释放激素（GHRH）以 GH/IGF-1 独立的方式直接激活受损心脏中的细胞修复机制。在实验性心肌梗死（MI）后，大鼠被随机分为 4 周治疗期，分别接受安慰剂（n = 14）、重组大鼠 GH（n = 8）或 JI-38（n = 8；每天 50μg/kg）。JI-38 不会升高血清 GH 或 IGF-1 水平，但可显著减轻损伤后的心脏功能下降和重塑程度。相反，GH 给药显著增加体重、心脏重量和循环 GH 和 IGF-1，但不能抵消心脏结构和功能的下降。JI-38 和 GH 均增加了心脏前体细胞的增殖水平，但只有 JI-38 增加了抗凋亡基因的表达。GHRH 受体可在心肌细胞上检测到，支持心脏信号转导的直接激活。总的来说，这些发现表明，在心脏中，GHRH 激动剂可以在 MI 后激活心脏修复，这表明心脏中存在一种基于 GHRH 的潜在信号通路。对一种有效的 GHRH 激动剂的反应表型具有治疗意义。
