Hypertrophic Preconditioning Attenuates Myocardial Ischaemia-Reperfusion Injury by Modulating SIRT3-SOD2-mROS-Dependent Autophagy
| العنوان: | Hypertrophic Preconditioning Attenuates Myocardial Ischaemia-Reperfusion Injury by Modulating SIRT3-SOD2-mROS-Dependent Autophagy |
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| المؤلفون: | Aijun Sun, Zheng Dong, Leilei Ma, Junbo Ge, Xingxu Wang, Yunzeng Zou, Kai-Yue Xin, Fei-juan Kong |
| المصدر: | Cell Proliferation |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Programmed cell death, autophagy, SOD2, Myocardial Infarction, Apoptosis, Myocardial Reperfusion Injury, Pharmacology, Muscle hypertrophy, SIRT3, 03 medical and health sciences, Mice, 0302 clinical medicine, Sirtuin 3, Medicine, Animals, Myocardial infarction, RNA, Small Interfering, Ischemic Preconditioning, Mice, Knockout, business.industry, Superoxide Dismutase, Myocardium, Autophagy, Cell Biology, General Medicine, Original Articles, medicine.disease, hypertrophic preconditioning, Mitochondria, Mice, Inbred C57BL, 030104 developmental biology, Coronary occlusion, 030220 oncology & carcinogenesis, Beclin-1, RNA Interference, Original Article, ischaemia‐reperfusion injury, business, Reactive Oxygen Species, Reperfusion injury |
| الوصف: | Background Ischaemic preconditioning elicited by brief periods of coronary occlusion and reperfusion protects the heart from a subsequent prolonged ischaemic insult. Here, we test the hypothesis that short‐term non‐ischaemic stimulation of hypertrophy renders the heart resistant to subsequent ischaemic injury. Methods and Results Transient transverse aortic constriction (TAC) was performed for 3 days in mice and then withdrawn for 4 days by aortic debanding, followed by subsequent exposure to myocardial ischaemia‐reperfusion (I/R) injury. Following I/R injury, myocardial infarct size and apoptosis were significantly decreased, and cardiac dysfunction was markedly improved in the TAC preconditioning group compared with the control group. Mechanistically, TAC preconditioning markedly suppressed I/R‐induced autophagy and preserved autophagic flux by deacetylating SOD2 via a SIRT3‐dependent mechanism. Moreover, treatment with an adenovirus encoding SIRT3 partially mimicked the effects of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. Furthermore, in vivo lentiviral‐mediated knockdown of Beclin 1 in the myocardium ameliorated the I/R‐induced impairment of autophagic flux and was associated with a reduction in cell death, whereas treatment with a lentivirus encoding Beclin 1 abolished the cardioprotective effect of TAC preconditioning. Conclusions The present study identifies TAC preconditioning as a novel strategy for induction of an endogenous self‐defensive and cardioprotective mechanism against cardiac injury. Specifically, TAC preconditioning reduced myocardial autophagic cell death in a SIRT3/SOD2 pathway‐dependent manner. Hypertrophic preconditioning exerted marked protective effects by eliminating mitochondrial‐derived superoxide and suppressing autophagic cell death. SIRT3 partially mimicked the effects of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. |
| تدمد: | 1365-2184 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c22ce7818225b11fff3239c4ad976bb5Test https://pubmed.ncbi.nlm.nih.gov/33973685Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c22ce7818225b11fff3239c4ad976bb5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652184 |
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