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乙醛脱氢酶2对低氧诱导的肺动脉高压的保护作用及机制研究.docx

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乙醛脱氢酶2对低氧诱导的肺动脉高压的保护作用及机制研究 Title:ProtectiveEffectsandMechanismsofAldehydeDehydrogenase2inHypoxia-InducedPulmonaryArterialHypertension Abstract: Pulmonaryarterialhypertension(PAH)isachronicprogressivedisordercharacterizedbyincreasedpulmonaryarterialpressure,leadingtorightheartfailureanddeath.Hypoxia-inducedPAHisadistinctclinicalsubtypeofPAHthatdevelopsunderconditionsofreducedoxygenavailability.Aldehydedehydrogenase2(ALDH2),anenzymeinvolvedinalcoholmetabolism,hasbeenrecentlyimplicatedintheprotectionagainstvariouscardiovasculardiseases.ThisreviewaimstoexploretheprotectiveeffectsandunderlyingmechanismsofALDH2inhypoxia-inducedPAH. Introduction: PAHisacomplexdiseaseinvolvingmultiplemolecularandcellularprocessesleadingtostructuralremodelingofpulmonaryarteries.Hypoxia,astateofreducedoxygenavailability,contributessignificantlytothedevelopmentandprogressionofPAH.ALDH2,anenzymepredominantlypresentinmitochondria,hasbeenshowntoplayavitalroleinmaintainingcellularhomeostasisandprotectingagainstoxidativestress.However,thespecificcontributionofALDH2tohypoxia-inducedPAHremainsunclear. ProtectiveEffectsofALDH2inHypoxia-inducedPAH: ALDH2hasbeendemonstratedtoconferprotectionagainsthypoxia-inducedPAHthroughvariousmechanisms.Firstly,ALDH2activationhasbeenobservedtoenhancemitochondrialfunction,attenuateoxidativestress,andinhibitapoptosisinpulmonaryarteryendothelialcells.Secondly,ALDH2activationpromotesthemetabolismofaldehydesandreactiveoxygenspecies,whichareknowntoplaycriticalrolesinvascularremodeling.Furthermore,ALDH2activationcanmodulatethelevelsofnitricoxideandcyclicguanosinemonophosphate,leadingtoimprovedvasodilationandreducedvascularresistance. MechanismsofALDH2-MediatedProtection: ALDH2exertsitsprotectiveeffectsthroughmultiplesignalingpathways.ActivationoftheALDH2-AMP-activatedproteinkinase(AMPK)pathwayenhancesmitochondrialfunctionandsuppresseshypoxia-inducedpulmonaryvascularremodeling.ALDH2hasalsobeenreportedtointeractwithvarioustranscriptionfactors,includinghypoxia-induciblefactor