Hypertrophic Preconditioning Attenuates Myocardial Ischaemia-Reperfusion Injury by Modulating SIRT3-SOD2-mROS-Dependent Autophagy.
Hypertrophic Preconditioning Attenuates Myocardial Ischaemia-Reperfusion Injury by Modulating SIRT3-SOD2-mROS-Dependent Autophagy.
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DOI：
10.1111/cpr.13051
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发表时间：
2021-07
影响因子：
8.5
通讯作者：
Ge JB
中科院分区：
文献类型：
--
作者：
Ma LL;Kong FJ;Dong Z;Xin KY;Wang XX;Sun AJ;Zou YZ;Ge JB
短暂的冠状动脉闭塞和再灌注引起的缺血预处理可保护心脏免受随后的长期缺血损伤。在这里，我们检验了短期非缺血性刺激肥大使心脏对随后的缺血性损伤具有抵抗力的假设。在小鼠中进行短暂的横向主动脉缩窄（TAC）3天，然后通过主动脉剥离撤回4天，随后暴露于心肌缺血-再灌注（I/R）损伤。与对照组相比，TAC预处理组心肌梗死面积和细胞凋亡明显减少，心功能明显改善。从机制上讲，TAC预处理通过SIRT 3依赖性机制使SOD 2脱乙酰化，显著抑制了I/R诱导的自噬，并保留了自噬通量。此外，用编码SIRT 3的腺病毒治疗部分模拟了肥大预处理的作用，而小鼠中SIRT 3的基因切除阻断了肥大预处理的心脏保护作用。此外，体内慢病毒介导的Beclin 1在心肌中的敲低改善了I/R诱导的自噬通量损伤，并与细胞死亡减少相关，而用编码Beclin 1的慢病毒治疗则消除了TAC预处理的心脏保护作用。本研究将TAC预处理确定为诱导内源性自我防御和心脏保护机制对抗心脏损伤的新策略。具体而言，TAC预处理以SIRT 3/SOD 2途径依赖性方式减少心肌自噬细胞死亡。肥大预处理通过清除线粒体源性超氧化物和抑制自噬性细胞死亡发挥显著的保护作用。SIRT 3部分模拟了肥厚预处理的作用，而小鼠中SIRT 3的基因切除阻断了肥厚预处理的心脏保护作用。
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. Transient transverse aortic constriction (TAC) was performed for 3 days in mice and then withdrawn for 4 days by aortic debanding, followed by subsequent exposure to myocardial ischaemia‐reperfusion (I/R) injury.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. 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.
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影响因子：
37.8
作者：
MURRY, CE;JENNINGS, RB;REIMER, KA
通讯作者：
REIMER, KA
影响因子：
2.2
作者：
Huang, Hsien-Hao;Lai, Chang-Chi;Huang, Cheng-Hsiung
通讯作者：
Huang, Cheng-Hsiung
影响因子：
9.5
作者：
Cabrera-Fuentes HA;Aragones J;Bernhagen J;Boening A;Boisvert WA;Bøtker HE;Bulluck H;Cook S;Di Lisa F;Engel FB;Engelmann B;Ferrazzi F;Ferdinandy P;Fong A;Fleming I;Gnaiger E;Hernández-Reséndiz S;Kalkhoran SB;Kim MH;Lecour S;Liehn EA;Marber MS;Mayr M;Miura T;Ong SB;Peter K;Sedding D;Singh MK;Suleiman MS;Schnittler HJ;Schulz R;Shim W;Tello D;Vogel CW;Walker M;Li QO;Yellon DM;Hausenloy DJ;Preissner KT
通讯作者：
Preissner KT
影响因子：
20.1
作者：
Gao E;Lei YH;Shang X;Huang ZM;Zuo L;Boucher M;Fan Q;Chuprun JK;Ma XL;Koch WJ
通讯作者：
Koch WJ
自噬参与远端肢体缺血后处理对正常小鼠（而非糖尿病小鼠）心肌缺血/再灌注损伤的心脏保护作用
影响因子：
3.7
作者：
Han Z;Cao J;Song D;Tian L;Chen K;Wang Y;Gao L;Yin Z;Fan Y;Wang C
通讯作者：
Wang C