Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway

Liu，Guang Zhong1,2; Xu，Wei3; Zang，Yan Xiang3; Lou，Qi3; Hang，Peng Zhou4; Gao，Qiang3; Shi，Hang3; Liu，Qi Yun1,2; Wang，Hong3; Sun，Xin1,2; Liu，Cheng1,2; Zhang，Peng1,2; Liu，Hua Dong1,2; Dong，Shao Hong1,2

2022-03-17

10.3389/fphar.2022.813272

Frontiers in Pharmacology   影响因子和分区

1663-9812

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.

acetylation atrial fibrillation Honokiol metabolism remodeling sirt3

SCI

英语

通讯

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000778233300001

FRONTIERS MEDIA SA

2-s2.0-85127911759

Scopus

1.Department of Cardiology,Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center,Shenzhen People’s Hospital,Shenzhen,China
2.Shenzhen People’s Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
3.Department of Cardiology,the First Affiliated Hospital,Harbin Medical University,Harbin,China
4.Department of Pharmacy,Clinical Medical College,Yangzhou University,Northern Jiangsu People's Hospital,Yangzhou,China

Liu，Guang Zhong,Xu，Wei,Zang，Yan Xiang,et al. Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway[J]. Frontiers in Pharmacology,2022,13.

Liu，Guang Zhong.,Xu，Wei.,Zang，Yan Xiang.,Lou，Qi.,Hang，Peng Zhou.,...&Dong，Shao Hong.(2022).Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway.Frontiers in Pharmacology,13.

Liu，Guang Zhong,et al."Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway".Frontiers in Pharmacology 13(2022).