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Sevoflurane Postconditioning Regulates Mitophagy Through the PINK1/Parkin Pathway to Alleviate Myocardial
Yanming Xue1, Liqun Jia2, Jianzhong Zhang1
1Department of Anesthesiology, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, Shandong, China.
Abstract:
This study investigates whether sevoflurane postconditioning (SpostC) alleviates myocardial microcirculatory reperfusion injury by regulating mitophagy via the PTEN-induced kinase 1 (PINK1)/Parkin pathway. A mouse model of myocardial ischemia/reperfusion (I/R) injury was established. Microvascular perfusion was assessed by immunofluorescence. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), endothelin-1 (ET-1), PINK1, Parkin, microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I, and P62 was analyzed by Western blotting (WB). Hematoxylin-eosin and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate vascular pathology and infarct size. In vitro, human cardiac microvascular endothelial cells (hCMECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), with assessments of cell viability (cell counting kit-8), barrier function (FITC-dextran permeability and transendothelial electrical resistance), cytoskeletal integrity (immunofluorescence), and mitophagy markers (WB). SpostC enhanced microvascular perfusion, reduced infarct size, suppressed excessive mitophagy, and restored endothelial function. These protective effects were reversed by either the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) or PINK1 overexpression. SpostC exerts protective effects on myocardial microcirculatory reperfusion injury by inhibiting the PINK1/Parkin-mediated mitophagy pathway.
Insights
Sevoflurane postconditioning protects the heart from reperfusion injury by inhibiting excessive mitophagy through the PINK1/Parkin pathway. This intervention improves microvascular function and reduces infarct size in myocardial ischemia/reperfusion injury.
Area of Science:
- Cardiology
- Cell Biology
- Pharmacology
Background:
- Myocardial ischemia/reperfusion (I/R) injury causes significant microcirculatory damage.
- Mitophagy, the selective degradation of mitochondria, plays a role in I/R injury.
- The PTEN-induced kinase 1 (PINK1)/Parkin pathway regulates mitophagy.
Purpose of the Study:
- To investigate if sevoflurane postconditioning (SpostC) alleviates myocardial microcirculatory reperfusion injury.
- To determine if SpostC regulates mitophagy via the PINK1/Parkin pathway.
Main Methods:
- Established a mouse model of myocardial I/R injury.
- Assessed microvascular perfusion, vascular pathology, and infarct size.
- Analyzed protein expression of key mitophagy and endothelial markers using Western blotting.
- Utilized in vitro models (hCMECs subjected to OGD/R) to assess cell viability, barrier function, and mitophagy.
Main Results:
- SpostC enhanced microvascular perfusion and reduced infarct size.
- SpostC suppressed excessive mitophagy and restored endothelial function.
- Inhibiting mitophagy (using CCCP) or overexpressing PINK1 reversed the protective effects of SpostC.
Conclusions:
- SpostC exerts protective effects against myocardial microcirculatory reperfusion injury.
- These protective effects are mediated by the inhibition of the PINK1/Parkin-mediated mitophagy pathway.
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