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Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia\/reperfusion (I\/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I\/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I\/R injury by activating the Parkin and nuclear receptor subfamily group A member 2\/optineurin (NR4A2\/OPTN) pathways, in turn resulting in increased levels of mitophagy within I\/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I\/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.<\/jats:p>","DOI":"10.3390\/ijms25063305","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T09:32:30Z","timestamp":1710495150000},"page":"3305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia\u2013Reperfusion Injury through NR4A2-Mediated Mitophagy"],"prefix":"10.3390","volume":"25","author":[{"given":"Yifan","family":"Yu","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Cai","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Guo","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Lin","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1038\/s41591-023-02513-2","article-title":"A new clinical classification of acute myocardial infarction","volume":"29","author":"Lindahl","year":"2023","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104565","DOI":"10.1016\/j.mvr.2023.104565","article-title":"Myocardial ischemia-reperfusion injury; Molecular mechanisms and prevention","volume":"149","author":"Liu","year":"2023","journal-title":"Microvasc. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6614009","DOI":"10.1155\/2021\/6614009","article-title":"Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments","volume":"2021","author":"Xiang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/SHK.0000000000000578","article-title":"Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO","volume":"46","author":"Cordaro","year":"2016","journal-title":"Shock"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2020.07.019","article-title":"Lipoproteins and lipids in cardiovascular disease: From mechanistic insights to therapeutic targeting","volume":"159","author":"Soppert","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121771","DOI":"10.1016\/j.lfs.2023.121771","article-title":"Multifunctional targetable liposomal drug delivery system in the management of leukemia: Potential, opportunities, and emerging strategies","volume":"325","author":"Pardhi","year":"2023","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/ics.12452","article-title":"Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: A comprehensive review","volume":"40","author":"Saez","year":"2018","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s11095-022-03242-w","article-title":"Spray Dried Rugose Lipid Particle Platform for Respiratory Drug Delivery","volume":"39","author":"Wang","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-biochem-013118-111902","article-title":"Exosomes","volume":"88","author":"Pegtel","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11883-020-00871-7","article-title":"Exosomes: Multifaceted Messengers in Atherosclerosis","volume":"22","author":"Wang","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.cmet.2022.02.011","article-title":"Secreted phospholipase A2 modifies extracellular vesicles and accelerates B cell lymphoma","volume":"34","author":"Kudo","year":"2022","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ghadami, S., and Dellinger, K. (2023). The lipid composition of extracellular vesicles: Applications in diagnostics and therapeutic delivery. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1198044"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1007\/s00125-014-3337-2","article-title":"Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice","volume":"57","author":"Aswad","year":"2014","journal-title":"Diabetologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6956","DOI":"10.1038\/ncomms7956","article-title":"Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis","volume":"6","author":"Deng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1002\/ijc.24249","article-title":"Induction of myeloid-derived suppressor cells by tumor exosomes","volume":"124","author":"Xiang","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1038\/s41401-018-0036-4","article-title":"Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases","volume":"39","author":"Ge","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.4049\/jimmunol.1002068","article-title":"Sphingosylphosphorylcholine stimulates CCL2 production from human umbilical vein endothelial cells","volume":"186","author":"Lee","year":"2011","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/jcmm.16101","article-title":"Sphingosylphosphorylcholine blocks ovariectomy-induced bone loss by suppressing Ca2+\/calmodulin-mediated osteoclast differentiation","volume":"25","author":"Lee","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116207","DOI":"10.1016\/j.taap.2022.116207","article-title":"Sphingosylphosphorylcholine ameliorates doxorubicin-induced cardiotoxicity in zebrafish and H9c2 cells by reducing excessive mitophagy and mitochondrial dysfunction","volume":"452","author":"Zhou","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118692","DOI":"10.1016\/j.lfs.2020.118692","article-title":"MicroRNA-155-5p\/EPAS1\/interleukin 6 pathway participated in the protection function of sphingosylphosphorylcholine to ischemic cardiomyocytes","volume":"264","author":"Yao","year":"2021","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"425191","DOI":"10.1155\/2010\/425191","article-title":"Intravenous sphingosylphosphorylcholine protects ischemic and postischemic myocardial tissue in a mouse model of myocardial ischemia\/reperfusion injury","volume":"2010","author":"Herzog","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"624122","DOI":"10.3389\/fendo.2020.624122","article-title":"Role of the Orphan Nuclear Receptor NR4A Family in T-Cell Biology","volume":"11","author":"Odagiu","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00395-022-00942-7","article-title":"Prolonged cardiac NR4A2 activation causes dilated cardiomyopathy in mice","volume":"117","author":"Ashraf","year":"2022","journal-title":"Basic. Res. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104279","DOI":"10.1016\/j.mvr.2021.104279","article-title":"NR4A2 alleviates cardiomyocyte loss and myocardial injury in rats by transcriptionally suppressing CCR5 and inducing M2 polarization of macrophages","volume":"140","author":"Miao","year":"2022","journal-title":"Microvasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"121210","DOI":"10.1016\/j.lfs.2022.121210","article-title":"Moxonidine ameliorates cardiac injury in rats with metabolic syndrome by regulating autophagy","volume":"312","author":"Rezq","year":"2023","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.3892\/etm.2021.10615","article-title":"Propofol protects H9C2 cells against hypoxia\/reoxygenation injury through miR-449a and NR4A2","volume":"22","author":"Qian","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1536\/ihj.21-856","article-title":"LincRNA-p21 Upregulates Nuclear Orphan Receptor Nr4a2 and Aggravates Myocardial Ischemia\/Reperfusion Injury via Targeting MiR-466i-5p","volume":"63","author":"Zhai","year":"2022","journal-title":"Int. Heart J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41420-017-0011-8","article-title":"NR4A2 protects cardiomyocytes against myocardial infarction injury by promoting autophagy","volume":"4","author":"Liu","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_30","first-page":"515","article-title":"Autotaxin and lysophospholipids in rheumatoid arthritis","volume":"11","author":"Bourgoin","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.7150\/thno.56035","article-title":"Exosomes in atherosclerosis: Performers, bystanders, biomarkers, and therapeutic targets","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Morelli, M.B., Shu, J., Sardu, C., Matarese, A., and Santulli, G. (2019). Cardiosomal microRNAs Are Essential in Post-Infarction Myofibroblast Phenoconversion. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010201"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.bbrc.2013.01.015","article-title":"Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia\/reperfusion injury","volume":"431","author":"Chen","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ijcard.2015.05.020","article-title":"Exosomes\/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium","volume":"192","author":"Wang","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Youn, S.W., Li, Y., Kim, Y.M., Sudhahar, V., Abdelsaid, K., Kim, H.W., Liu, Y., Fulton, D.J., Ashraf, M., and Tang, Y. (2019). Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis. Antioxidants, 8.","DOI":"10.3390\/antiox8010018"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1169471","DOI":"10.3389\/fimmu.2023.1169471","article-title":"Endothelial exosomes work as a functional mediator to activate macrophages","volume":"14","author":"Lin","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.omtn.2021.02.005","article-title":"Exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial I\/R injury via p53-mediated autophagy and apoptosis","volume":"23","author":"Su","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e156624","DOI":"10.1172\/JCI156624","article-title":"Sortilin drives hypertension by modulating sphingolipid\/ceramide homeostasis and by triggering oxidative stress","volume":"132","author":"Varzideh","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/MCA.0000000000000997","article-title":"Cellular mechanisms and pathways in myocardial reperfusion injury","volume":"32","author":"Valikeserlis","year":"2021","journal-title":"Coron. Artery Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cardiores.2005.05.013","article-title":"Sphingosylphosphorylcholine-induced vasoconstriction of pulmonary artery: Activation of non-store-operated Ca2+ entry","volume":"68","author":"Thomas","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1161\/HYPERTENSIONAHA.107.104802","article-title":"Low concentrations of sphingosylphosphorylcholine enhance pulmonary artery vasoreactivity: The role of protein kinase C delta and Ca2+ entry","volume":"51","author":"Snetkov","year":"2008","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cellsig.2004.11.004","article-title":"Sphingosylphosphorylcholine generates reactive oxygen species through calcium-, protein kinase Cdelta- and phospholipase D-dependent pathways","volume":"17","author":"Jeon","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1002\/jcb.21141","article-title":"Sphingosylphosphorylcholine induces apoptosis of endothelial cells through reactive oxygen species-mediated activation of ERK","volume":"100","author":"Jeon","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1002\/jcp.22632","article-title":"Regulation of apoptosis and autophagy by sphingosylphosphorylcholine in vascular endothelial cells","volume":"226","author":"Ge","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bhattarai, S., Sharma, S., Subedi, U., Ara, H., Shum, A., Milena, M., Bhuiyan, M.S., Kidambi, S., Sun, H., and Miriyala, S. (2022). The ATX-LPA Axis Regulates Vascular Permeability during Cerebral Ischemic-Reperfusion. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084138"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.chembiol.2022.12.006","article-title":"Autotaxin facilitates selective LPA receptor signaling","volume":"30","author":"Borza","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bcp.2019.03.035","article-title":"Targeting the autotaxin\u2014Lysophosphatidic acid receptor axis in cardiovascular diseases","volume":"164","author":"Zhao","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4629189","DOI":"10.1155\/2020\/4629189","article-title":"Astaxanthin Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Oxidative Stress-Induced Mitochondrial Dysfunction","volume":"2020","author":"Chen","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yjmcc.2020.09.011","article-title":"Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction","volume":"149","author":"Tripathi","year":"2020","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"24488","DOI":"10.1074\/jbc.M114.577213","article-title":"Decreased amyloid-\u03b2 pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice","volume":"289","author":"Yuyama","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Weng, X., Tan, H., Huang, Z., Chen, J., Zhang, N., Wang, Q., Li, Q., Gao, J., Sun, D., and Yakufu, W. (2022). Targeted delivery and ROS-responsive release of Resolvin D1 by platelet chimeric liposome ameliorates myocardial ischemia-reperfusion injury. J. Nanobiotechnology, 20.","DOI":"10.1186\/s12951-022-01652-x"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.7150\/thno.30853","article-title":"Design strategies and application progress of therapeutic exosomes","volume":"9","author":"Liu","year":"2019","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2298514","DOI":"10.1080\/10717544.2023.2298514","article-title":"Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: Current strategies and future prospective","volume":"31","author":"Li","year":"2024","journal-title":"Drug Deliv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e008737","DOI":"10.1161\/JAHA.118.008737","article-title":"Engineered Exosomes With Ischemic Myocardium-Targeting Peptide for Targeted Therapy in Myocardial Infarction","volume":"7","author":"Wang","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"C12","DOI":"10.1152\/ajpcell.00131.2021","article-title":"Mitochondrial redox regulation and myocardial ischemia-reperfusion injury","volume":"322","author":"Chen","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/physiol.00030.2017","article-title":"Mitophagy in Cardiomyocytes and in Platelets: A Major Mechanism of Cardioprotection Against Ischemia\/Reperfusion Injury","volume":"33","author":"Zhang","year":"2018","journal-title":"Physiology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41586-021-04340-2","article-title":"Activation mechanism of PINK1","volume":"602","author":"Gan","year":"2022","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/sj.bjp.0705934","article-title":"Cardiovascular effects of sphingosine-1-phosphate and other sphingomyelin metabolites","volume":"143","author":"Alewijnse","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41580-022-00542-2","article-title":"The mechanisms and roles of selective autophagy in mammals","volume":"24","author":"Vargas","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/15548627.2019.1628520","article-title":"PHB2 (prohibitin 2) promotes PINK1-PRKN\/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis","volume":"16","author":"Yan","year":"2020","journal-title":"Autophagy"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1080\/15548627.2020.1839286","article-title":"Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3","volume":"17","author":"Liu","year":"2021","journal-title":"Autophagy"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhang, H., Li, Z., Yan, X., Li, Y., and Liu, S. (2021). microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2\/NF-\u03baB axis. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-020-01742-4"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2023.01.016","article-title":"MORN4 protects cardiomyocytes against ischemic injury via MFN2-mediated mitochondrial dynamics and mitophagy","volume":"196","author":"Zhou","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10924","DOI":"10.1080\/21655979.2021.1995994","article-title":"Naringenin alleviates myocardial ischemia\/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) \/System xc-\/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis","volume":"12","author":"Xu","year":"2021","journal-title":"Bioengineered"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1038\/s41467-022-31548-1","article-title":"Cardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s10495-020-01639-9","article-title":"Sphingosylphosphorylcholine alleviates hypoxia-caused apoptosis in cardiac myofibroblasts via CaM\/p38\/STAT3 pathway","volume":"25","author":"Li","year":"2020","journal-title":"Apoptosis"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8433464","DOI":"10.1155\/2022\/8433464","article-title":"Adiponectin Protects Hypoxia\/Reoxygenation-Induced Cardiomyocyte Injury by Suppressing Autophagy","volume":"2022","author":"Guo","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Hou, S., Song, Y., Sun, D., Zhu, S., and Wang, Z. (2021). Xanthohumol-Induced Rat Glioma C6 Cells Death by Triggering Mitochondrial Stress. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094506"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"113716","DOI":"10.1016\/j.ecoenv.2022.113716","article-title":"Exposure to zinc induces lysosomal-mitochondrial axis-mediated apoptosis in PK-15 cells","volume":"241","author":"Yang","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"115355","DOI":"10.1016\/j.taap.2020.115355","article-title":"CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy","volume":"410","author":"Zhang","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.freeradbiomed.2020.01.016","article-title":"Butyrate alleviates oxidative stress by regulating NRF2 nuclear accumulation and H3K9\/14 acetylation via GPR109A in bovine mammary epithelial cells and mammary glands","volume":"152","author":"Guo","year":"2020","journal-title":"Free Radic. Biol. 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