CTRP3 protected against doxorubicin-induced cardiac dysfunction, inflammation and cell death via activation of Sirt1

被引:133
作者
Yuan, Yu -Pei [1 ,2 ,3 ]
Ma, Zhen-Guo [1 ,2 ,3 ]
Zhang, Xin [1 ,2 ,3 ]
Xu, Si-Chi [1 ,2 ,3 ]
Zeng, Xiao-Feng [1 ,2 ,3 ]
Yang, Zheng [1 ,2 ,3 ]
Deng, Wei [1 ,2 ,3 ]
Tang, Qi-Zhu [1 ,2 ,3 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Cardiol, Jiefang Rd 238, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Hubei, Peoples R China
[3] Hubei Key Lab Cardiol, Wuhan 430060, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
Doxorubicin; C1q/tumour necrosis factor-related protein-3; Inflammation; Apoptosis; Silent information regulator 1; OXIDATIVE STRESS; MITOCHONDRIAL BIOGENESIS; CARDIOMYOCYTE APOPTOSIS; CARDIOTOXICITY; MICE; INTERLEUKIN-1; HYPERTROPHY; ANTAGONIST; PROTEIN-3; MECHANISM;
D O I
10.1016/j.yjmcc.2017.10.008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (15 mg/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.
引用
收藏
页码:38 / 47
页数:10
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