Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway

被引:14
|
作者
Liu, Guang Zhong [1 ,2 ,3 ]
Xu, Wei [4 ]
Zang, Yan Xiang [4 ]
Lou, Qi [4 ]
Hang, Peng Zhou [5 ]
Gao, Qiang [4 ]
Shi, Hang [4 ]
Liu, Qi Yun [1 ,2 ,3 ]
Wang, Hong [4 ]
Sun, Xin [1 ,2 ,3 ]
Liu, Cheng [1 ,2 ,3 ]
Zhang, Peng [1 ,2 ,3 ]
Liu, Hua Dong [1 ,2 ,3 ]
Dong, Shao Hong [1 ,2 ,3 ]
机构
[1] Shenzhen Peoples Hosp, Shenzhen Cardiovasc Minimally Invas Med Engn Tech, Dept Cardiol, Shenzhen, Peoples R China
[2] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Guangzhou, Peoples R China
[3] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China
[4] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin, Peoples R China
[5] Yangzhou Univ, Northern Jiangsu Peoples Hosp, Clin Med Coll, Dept Pharm, Yangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Honokiol; atrial fibrillation; metabolism remodeling; sirt3; acetylation; FATTY-ACID OXIDATION; ENERGY-METABOLISM; QUANTITATIVE PROTEOMICS; ACETYLATION; DEHYDROGENASE; SIRTUINS; DEACETYLATION; PROTECTS; STRESS; MODEL;
D O I
10.3389/fphar.2022.813272
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and Purpose: Atrial metabolic remodeling plays a critical role in the pathogenesis of atrial fibrillation (AF). Sirtuin3 (Sirt3) plays an important role in energy homeostasis. However, the effect of Sirt3 agonist Honokiol (HL) on AF is unclear. Therefore, the aim of this study is to determine the effect of HL on atrial metabolic remodeling in AF and to explore possible mechanisms.Experimental Approach: irt3 and glycogen deposition in left atria of AF patients were examined. Twenty-one rabbits were divided into sham, P (pacing for 3 weeks), P + H treatment (honokiol injected with pacing for 3 weeks). The HL-1 cells were subjected to rapid pacing at 5 Hz for 24 h, in the presence or absence of HL and overexpression or siRNA of Sirt3 by transfection. Metabolic factors, circulating metabolites, atrial electrophysiology, ATP level, and glycogens deposition were detected. Acetylated protein and activity of its enzymes were detected.Key Results: Sirt3 was significantly down-regulated in AF patients and rabbit/HL-1cell model, resulting in the abnormal expression of its downstream metabolic key factors, which were significantly restored by HL. Meanwhile, AF induced an increase of the acetylation level in long-chain acyl-CoA dehydrogenase (LCAD), AceCS2 and GDH, following decreasing of activity of it enzymes, resulting in abnormal alterations of metabolites and reducing of ATP, which was inhibited by HL. The Sirt3 could regulate acetylated modification of key metabolic enzymes, and the increase of Sirt3 rescued AF induced atrial metabolic remodeling.Conclusion and Implications: HL inhibited atrial metabolic remodeling in AF via the Sirt3 pathway. The present study may provide a novel therapeutical strategy for AF.
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页数:13
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