免疫介导心脏疾病新策略.ppt

NewStrategiesforImmune-mediatedHeartDiseasesMitsuakiIsobeDepartmentofCardiovascularMedicineTokyoMedicalandDentalUniversityChina-JapanCardiovascularForum2008

Immune-mediatedheartdiseasesIschemia-reperfusioninjuryAtherosclerosisRestenosisCardiacallograftrejectionCardiacallograftvasculopathyMyocarditisCongestiveheartfailureArrhythmia

Immune-mediatedheartdiseasesIschemia-reperfusioninjuryAtherosclerosisRestenosisCardiacallograftrejectionCardiacallograftvasculopathyMyocarditisCongestiveheartfailureArrhythmia

InflammationincoronaryarteriosclerosisandatherogenesisPPARγ(Peroxisomeproliferator-activatedreceptor-γ)NFκB

AcutecardiacallograftrejectionEctopichearttransplantionrecipients:C3H/Hedonors:BALB/cfullmismatchAdministrationofpioglitazone(3mg/kg/day)totherecipientmice.Murinehearttransplantation

SurvivalRatePostoperativeDaysPioglitazone(3mg/kg/day)ControlchowProlongationofheartgraftbypioglitazone10.80.60.40.2010203040506070**p0.05

0.80.60.40.20OpticalDensityRR+Pio10-6MR+SR+S+Pio10-6MR+S+Pio10-7MR+S+Pio10-5MR:responder(recipient)S:stimulator(donor)Pio:pioglitazone***p0.05SuppressionofTcellProliferationbyPioglitazoneinMixedLymphocyteReaction*

Chroniccardiacrejection

Graftarterialdisease(GAD)RCALADLCX8-y-oboySmallarteriesMyocardiumAcceleratedcoronarysclerosisGraftvasculopathyCardiacallograftvasculopathyPathology:DiffuseintimalthickeningofsmalltolargecoronaryarteriesPathology:DiffuseintimalthickeningofsmalltolargecoronaryarteriesRiskfactors:CMVinfectionepisodesofacuterejectionRiskfactors:CMVinfectionepisodesofacuterejectionTherapy:?Therapy:?Progression:monthstoyearsProgression:monthstoyears

ChroniccardiacallograftrejectionCardiacallograftvasculopathyrecipients:C57BL/6donors:Bm12classIImismatch-1071421283