Yang Chunyan, Liu Zhonghui, Liu Kai, Yang Ping
Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China ; Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
PLoS One. 2014 Jan 21;9(1):e85785. doi: 10.1371/journal.pone.0085785. eCollection 2014.
Ghrelin is a novel growth hormone-releasing peptide administered to treat chronic heart failure (CHF). However, the underlying mechanism of its protective effects against heart failure (HF) remains unclear.
A total of 68 patients with CHF and 20 healthy individuals were included. The serum levels of Angiotensin II (Ang II) and ghrelin were measured using ELISA. The results showed that Ang II and ghrelin were both significantly increased in CHF patients and that the ghrelin levels were significantly positively correlated with Ang II. The left anterior descending coronary artery was ligated to establish a rat model of CHF, and cultured cardiomyocytes from neonatal rats were stimulated with Ang II to explore the role of ghrelin in CHF. The results showed that ghrelin inhibited cardiomyocyte apoptosis both in vivo and in vitro. Furthermore, caspase-3 expression was examined, and the results revealed that Ang II induces cardiomyocyte apoptosis through the caspase-3 pathway, whereas ghrelin inhibits this action. Lastly, to further elucidate the mechanism by which ghrelin inhibits Ang II action, the expression of the AT1 and AT2 receptors was evaluated; the results showed that Ang II up-regulates the AT1 and AT2 receptors in cardiomyocytes, whereas ghrelin inhibits AT1 receptor up-regulation but does not affect AT2 receptor expression.
These data suggest that the serum levels of ghrelin are significantly positively correlated with Ang II in CHF patients and that ghrelin can inhibit Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R, thereby playing a role in preventing HF.
胃饥饿素是一种用于治疗慢性心力衰竭（CHF）的新型生长激素释放肽。然而，其对心力衰竭（HF）保护作用的潜在机制仍不清楚。
共纳入68例CHF患者和20名健康个体。采用酶联免疫吸附测定法（ELISA）检测血清血管紧张素II（Ang II）和胃饥饿素水平。结果显示，CHF患者的Ang II和胃饥饿素水平均显著升高，且胃饥饿素水平与Ang II呈显著正相关。结扎左冠状动脉前降支建立CHF大鼠模型，用Ang II刺激新生大鼠培养的心肌细胞，以探讨胃饥饿素在CHF中的作用。结果表明，胃饥饿素在体内和体外均抑制心肌细胞凋亡。此外，检测了半胱天冬酶-3（caspase-3）的表达，结果显示Ang II通过caspase-3途径诱导心肌细胞凋亡，而胃饥饿素抑制这一作用。最后，为进一步阐明胃饥饿素抑制Ang II作用的机制，评估了AT1和AT2受体的表达；结果显示，Ang II上调心肌细胞中的AT1和AT2受体，而胃饥饿素抑制AT1受体上调，但不影响AT2受体表达。
这些数据表明，CHF患者血清胃饥饿素水平与Ang II显著正相关，胃饥饿素可通过下调AT1R抑制Ang II诱导的心肌细胞凋亡，从而在预防HF中发挥作用。
