Yuan Ming-Jie, Huang He, Huang Cong-Xin
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Lett. 2014 Sep;8(3):969-971. doi: 10.3892/ol.2014.2245. Epub 2014 Jun 12.
The gastrointestinal hormone ghrelin has important cardiovascular protective effects, however, its specific mechanisms are not yet completely understood. Recent studies have shown that the ghrelin receptor, growth hormone secretagogue receptor type 1a (GHSR-1a), regulates cell proliferation, apoptosis and inflammation-related signaling pathways. In human aortic endothelial cells, ghrelin activates NO production through AMP-activated protein kinase (AMPK) and Akt activation, and these effects can be blocked by knockdown of GHSR-1a. Obese mice have been found to exhibit an increased GHSR-1a content and expression in the heart, associated with an increase in phosphatidylinositol 3-kinase (PI3K) content and an increase AKT content and phosphorylation. Furthermore, GHSR-1a expression was observed to be increased in heart failure after myocardial infarction (MI) in rats. Given such complexity in GHSR-1a signaling and crosstalk with the AMPK and PI3K/Akt signaling pathways, both of which are well-known factors involved in cardiac remodeling after MI, we speculate that GHSR-1a signaling may play a regulatory role in cardiac protection and hope to identify new drugs targets. However, to date, no direct association between GHSR-1a and cardiac remodeling has been found. Therefore, further studies are required.
胃肠道激素胃饥饿素具有重要的心血管保护作用，然而，其具体机制尚未完全明确。最近的研究表明，胃饥饿素受体，即1a型生长激素促分泌素受体（GHSR-1a），可调节细胞增殖、凋亡以及炎症相关信号通路。在人主动脉内皮细胞中，胃饥饿素通过激活AMP活化蛋白激酶（AMPK）和Akt来促进一氧化氮（NO）生成，而这些效应可通过敲低GHSR-1a来阻断。已发现肥胖小鼠心脏中的GHSR-1a含量及表达增加，同时磷脂酰肌醇3激酶（PI3K）含量增加，AKT含量及磷酸化水平也增加。此外，在大鼠心肌梗死（MI）后的心力衰竭中，观察到GHSR-1a表达增加。鉴于GHSR-1a信号传导以及与AMPK和PI3K/Akt信号通路的相互作用存在如此复杂性，而这两条信号通路都是MI后心脏重塑中众所周知的相关因素，我们推测GHSR-1a信号传导可能在心脏保护中发挥调节作用，并希望确定新的药物靶点。然而，迄今为止，尚未发现GHSR-1a与心脏重塑之间存在直接关联。因此，需要进一步研究。
