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1、DOI:10.1111/j.1365-2362.2009.02153.xSHORTREPORTSARS-coronavirusmodulationofmyocardialACE2expressionandin?ammationinpatientswithSARS*,1*§?G.Y.Oudit,Z.Kassiri,C.Jiang,P.P.Liu,S.M.Poutanen,J.M.PenningerandJ.Butany*UniversityofAlberta,Edmonton,Canada,PekingUnionMedicalCollege,Beijing,China,Universi
2、tyHealthNetwork,§?UniversityofToronto,Toronto,Canada,MountSinaiHospital,Toronto,Canada,InstituteforMolecularBiotechnologyoftheAustrianAcademyofSciences,Vienna,AustriaABSTRACTBackgroundAngiotensinconvertingenzyme2(ACE2),amonocarboxylasethatdegradesangiotensinIItoangiotensin17,isalsothefunctional
3、receptorforsevereacuterespiratorysyndrome(SARS)coronavirus(SARS-CoV)andishighlyexpressedinthelungsandheart.PatientswithSARSalsosufferedfromcardiacdiseaseincludingarrhythmias,suddencardiacdeath,andsystolicanddiastolicdysfunction.MaterialsandmethodsWestudiedmiceinfectedwiththehumanstrainoftheSARS
4、-CoVandencephalomyo-carditisvirusandexaminedACE2mRNAandproteinexpression.AutopsyheartsamplesfrompatientswhosuccumbedtotheSARScrisisinToronto(Canada)wereusedtoinvestigatetheimpactofSARSonmyocardialstructure,in?ammationandACE2proteinexpression.ResultsPulmonaryinfectionwiththehumanSARS-CoVinmicele
5、dtoanACE2-dependentmyocardialinfectionwithamarkeddecreaseinACE2expressioncon?rmingacriticalroleofACE2inmediatingSARS-CoVinfectionintheheart.TheSARS-CoVviralRNAwasdetectedin35%(720)ofautopsiedhumanheartsamplesobtainedfrompatientswhosuccumbedtotheSARScrisisduringtheTorontoSARSoutbreak.Macrophage-
6、speci?cstainingshowedamarkedincreaseinmacrophagein?ltrationwithevidenceofmyocardialdamageinpatientswhohadSARS-CoVintheirhearts.ThepresenceofSARS-CoVintheheartwasalsoassociatedwithmarkedreductionsinACE2proteinexpression.ConclusionsOurdatashowthatSARS-CoVcanmediatemyocardialin?ammationanddamageas
7、sociatedwithdown-regulationofmyocardialACE2system,whichmayberesponsibleforthemyocardialdysfunctionandadversecardiacoutcomesinpatientswithSARS.KeywordsAngiotensinconvertingenzyme2,heart,macrophage,SARScoronarvirus,severeacuterespir
