Downregulated endogenous sulfur dioxide/aspartate aminotransferase pathway is involved in angiotensin II-stimulated cardiomyocyte autophagy and myocardial hypertrophy in mice

被引:36
作者
Chen, Qinghua [1 ]
Zhang, Lulu [1 ]
Chen, Siyao [2 ,3 ]
Huang, Yaqian [1 ]
Li, Kun [4 ]
Yu, Xiaoqi [4 ]
Wu, Huijuan [1 ]
Tian, Xiaoyu [1 ]
Zhang, Chunyu [1 ]
Tang, Chaoshu [5 ,6 ]
Du, Junbao [1 ]
Jin, Hongfang [1 ,6 ]
机构
[1] Peking Univ, Hosp 1, Dept Pediat, Xi An Men Str 1, Beijing 100034, Peoples R China
[2] Guangdong Gen Hosp, Guangdong Cardiovasc Inst, Dept Cardiac Surg, Guangzhou, Guangdong, Peoples R China
[3] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China
[4] Sichuan Univ, Coll Chem, Minist Educ, Key Lab Green Chem & Technol, Chengdu 610064, Peoples R China
[5] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing, Peoples R China
[6] Minist Educ, Key Lab Mol Cardiol, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
Angiotensin II; Myocardial hypertrophy; Autophagy; Sulfur dioxide; DIOXIDE; INHIBITION; EXPRESSION; RAT;
D O I
10.1016/j.ijcard.2016.09.111
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The study was designed to investigate if endogenous sulfur dioxide (SO2) was involved in cardiomyocyte autophagy and myocardial hypertrophy stimulated by angiotensin II (Ang II). Methods: Thirty-two C57 mice were randomly divided into control, SO2, Ang II and Ang II+ SO2 groups. Human myocardial cell line H9c2 was divided into four groups including control, SO2, Ang II and Ang II + SO2 groups. Blood pressure and myocardial hypertrophy of the mice were measured two weeks after Ang II administration. LC3 II/I ratio, and Beclin1, Atg4B and p62 expressions were determined both in vivo and in vitro. Autophagosome was observed in H9c2 cells with confocal microscope. Endogenous SO2 generation and aspartate aminotransferase (AAT) expression were measured. Results: In animal studies, hypertension andmyocardial hypertrophy developed two weeks after Ang II administration. LC3 II/I ratio and Beclin1 and Atg4B expressions were markedly elevated (P all <0.05), but p62 expression was lowered (P < 0.05) both in vivo and in vitro. Compared with control group, endogenous SO2 levels, AAT activity and AAT2 expression were obviously down-regulated (P all <0.05). However, SO2 donor significantly reduced Ang II-induced myocardial hypertrophy in mice. LC3 II/I ratio and Beclin1 and Atg4B expressions were down-regulated (P all <0.05) but p62 expression was significantly increased (P < 0.05) in the presence of SO2 both in vivo and in vitro. Conclusion: Down-regulated endogenous SO2/AAT2 pathway might be involved in the pathogenesis of myocardial hypertrophy. SO2 prevented Ang II -induced myocardial hypertrophy accompanied by down-regulating cardiomyocyte autophagy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:392 / 401
页数:10
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