Polydatin protects cardiomyocytes against myocardial infarction injury by activating Sirt3.
Myocardial infarction (MI), which is characterized by chamber dilation and left ventricular (LV) dysfunction, represents a major cause of morbidity and mortality worldwide. Polydatin (PD), a monocrystalline and polyphenolic drug isolated from a traditional Chinese herb (Polygonum cuspidatum), alleviates mitochondrial dysfunction. We investigated the effects and underlying mechanisms of PD in post-MI cardiac dysfunction. We constructed an MI model by left anterior descending (LAD) coronary artery ligation using wild-type (WT) and Sirt3 knockout (Sirt3-/-) mice. Cardiac function, cardiomyocytes autophagy levels, apoptosis and mitochondria biogenesis in mice that underwent cardiac MI injury were compared between groups. PD significantly improved cardiac function, increased autophagy levels and decreased cardiomyocytes apoptosis after MI. Furthermore, PD improved mitochondrial biogenesis, which is evidenced by increased ATP content, citrate synthase (CS) activity and complexes I/II/III/IV/V activities in the cardiomyocytes subjected to MI injury. Interestingly, Sirt3 knockout abolished the protective effects of PD administration. PD inhibited apoptosis in cultured neonatal mouse ventricular myocytes subjected to hypoxia for 6h to simulate MI injury. PD increased GFP-LC3 puncta, and reduced the accumulation of protein aggresomes and p62 in cardiomyocytes after hypoxia. Interestingly, the knock-down of Sirt3 nullified the PD-induced beneficial effects. Thus, the protective effects of PD are associated with the up-regulation of autophagy and improvement of mitochondrial biogenesis through Sirt3 activity.
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Mingming
M
Zhang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Zhijing
Z
Zhao
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Min
M
Shen
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Yingmei
Y
Zhang
State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Jianhong
J
Duan
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Yanjie
Y
Guo
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Dongwei
D
Zhang
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jianqiang
J
Hu
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jie
J
Lin
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wanrong
W
Man
Department of Anesthesia, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: lichao.hou@foxmail.com.
Lichao
L
Hou
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China,. Electronic address: wanghc@fmmu.edu.cn.
Haichang
H
Wang
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China,. Electronic address: wintersun3@gmail.com.
Dongdong
D
Sun
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D001678:Organelle Biogenesis; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
D005960:Glucosides; C525046:Sirt3 protein, mouse; D013267:Stilbenes; D056566:Sirtuin 3; C058229:polydatin
Autophagy; Mitochondria; Myocardial infarction, MI; Polydatin, PD; Sirt3