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Elabela对多柔比星介导的心脏毒性的保护作用及其机制研究.docx

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Elabela对多柔比星介导的心脏毒性的保护作用及其机制研究 Title:Elabela-mediatedCardioprotectiveEffectsagainstDoxorubicin-inducedCardiotoxicityandItsMechanisms Abstract: Doxorubicin(Dox)isawidelyusedchemotherapeuticagent;however,itsuseislimitedduetosignificantcardiotoxicsideeffects,includingmyocardialdysfunctionandheartfailure.Elabela(ELA)hasrecentlyemergedasapotentialcardioprotectivefactor.ThispaperaimstoreviewthecurrentresearchontheprotectiveeffectsofELAagainstDox-inducedcardiotoxicityandelucidateitsunderlyingmechanisms. 1.Introduction Doxorubicinisananthracyclinewidelyusedforthetreatmentofvariouscancers.Unfortunately,itsclinicalutilityislimitedbydose-dependentcardiotoxicity,whichresultsincardiomyocytedamage,oxidativestress,inflammation,andapoptosis.Thesemechanismscollectivelycontributetoprogressivecardiacdysfunctionandheartfailure.Therefore,thereisanurgentneedtoidentifynoveltherapeuticstrategiestomitigateDox-inducedcardiotoxicity. 2.RoleofElabelaintheCardiovascularSystem Elabela,alsoknownasApelaorToddler,isapeptidehormonethathasgainedincreasingattentionforitsprotectiveeffectsonthecardiovascularsystem.ELAexertsitseffectsthroughitsreceptor,theapelinreceptor(APJ).ELAandAPJareexpressedinvarioustissues,includingtheheart,bloodvessels,andendothelialcells.ELAhasbeenshowntohavebeneficialeffectsoncardiacdevelopment,angiogenesis,andcontractility.Italsopossessesanti-inflammatoryandanti-apoptoticproperties,makingitapotentialcandidateforcardioprotection. 3.Elabela'sCardioprotectiveEffectsagainstDoxorubicin-inducedCardiotoxicity RecentstudieshavedemonstratedthatELAcanprotectagainstDox-inducedcardiotoxicity.ELAadministrationwasfoundtoattenuatecardiacdysfunction,reducemyocardialinjury,andinhibitcardiomyocyteapoptosisinanimalmodels.ELAtreatmentalsomitigatedoxidativestressandinflammation,twokeyfactorscontributingtoDox-inducedcardiacdamage.ThesefindingssuggestthatELAmayhavethepotentialtoameliorateDox-inducedcardiactoxicity. 4.MechanismsofElabela-mediatedCardioprotectionagainstDoxorubicin-inducedCardiotoxicity