CTRP3 通过激活 Sirt1 来防止阿霉素引起的心脏功能障碍、炎症和细胞死亡。
CTRP3 protected against doxorubicin-induced cardiac dysfunction, inflammation and cell death via activation of Sirt1.
机构信息
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China.
出版信息
J Mol Cell Cardiol. 2018 Jan;114:38-47. doi: 10.1016/j.yjmcc.2017.10.008. Epub 2017 Oct 20.
BACKGROUND
Inflammation and myocytes apoptosis play critical roles in the development of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found that C1q/tumour necrosis factor-related protein-3 (CTRP3) could inhibit cardiac inflammation and apoptosis of myocytes but its role in DOX-induced heart injury remains largely unknown. Our study aimed to investigate whether CTRP3 protected against DOX-induced heart injury and the underlying mechanism.
METHODS
We overexpressed CTRP3 in the hearts using an adeno-associated virus system. The mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to induce short-term model for cardiomyopathy. The morphological examination and biochemical analysis were used to evaluate the effects of CTRP3. H9C2 cells were used to verify the protective role of CTRP3 in vitro.
RESULTS
Myocardial CTRP3 protein levels were reduced in DOX-treated mice. Cardiac specific-overexpression of CTRP3 preserved heart dysfunction, and attenuated cardiac inflammation and cell loss induced by DOX in vivo and in vitro. CTRP3 could activate silent information regulator 1 (Sirt1) in vivo and in vitro. Moreover, specific inhibitor of Sirt1 and the silence of Sirt1 could abolish the protective effects of CTRP3 against DOX-induced inflammation and apoptosis.
CONCLUSION
CTRP3 protected against DOX-induced heart injury via activation of Sirt1. CTRP3 has therapeutic potential for the treatment of DOX cardiotoxicity.
背景
炎症和心肌细胞凋亡在多柔比星（DOX）诱导的心脏毒性发展中起着关键作用。我们之前的研究发现，C1q/肿瘤坏死因子相关蛋白-3（CTRP3）可以抑制心肌炎症和细胞凋亡，但它在 DOX 诱导的心脏损伤中的作用在很大程度上尚不清楚。我们的研究旨在探讨 CTRP3 是否可以预防 DOX 诱导的心脏损伤及其潜在机制。
方法
我们使用腺相关病毒系统在心脏中过表达 CTRP3。用 DOX（15mg/kg）单次腹腔注射诱导小鼠产生短期心肌病模型。采用形态学检查和生化分析来评估 CTRP3 的作用。体外使用 H9C2 细胞验证 CTRP3 的保护作用。
结果
DOX 处理的小鼠心肌中 CTRP3 蛋白水平降低。心脏特异性过表达 CTRP3 可保持心脏功能，减轻 DOX 体内和体外诱导的心脏炎症和细胞丢失。CTRP3 可在体内和体外激活沉默信息调节因子 1（Sirt1）。此外，Sirt1 的特异性抑制剂和 Sirt1 的沉默可消除 CTRP3 对 DOX 诱导的炎症和凋亡的保护作用。
结论
CTRP3 通过激活 Sirt1 来保护 DOX 诱导的心脏损伤。CTRP3 具有治疗 DOX 心脏毒性的潜力。
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