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高级病生动脉硬化讲座硕士班.pptx

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会计学“Chronicinflammatorydisorderofintimaoflargebloodvesselscharacterisedbyformationoffibrofattyplaquescalledatheroma”. Hardeningofarteries-ArteriosclerosisMacrophages T-lymphocytes AtherosclerosisLipidmetabolismimbalanceClassificationoflipidsandlipoproteinsCharacteristicsoflipoproteinsDigestionandmetabolismofdietaryfatHDLmetabolismandreversecholesteroltransportCholesteroleffluxandreversecholesteroltransportismodulatedbytworeceptorsPPARαactivatorsinducecholesteroleffluxandreversecholesteroltransportHDLmetabolism:5keygenesPPARα:apoA-l,apoA-ll,LPL,ABCA-1andSR-BIexpressionPPARaactivatorsinducecholesteroleffluxfromhumanmacrophagesCLA-1/SR-BIproteinmaypromotecholesterolremovalfromperipheralcellsCLA-1expressionisregulatedbyPPARαactivatorsindifferentiatedhumanmacrophagesPPARαactivatorsinducecholesteroleffluxandreversecholesteroltransportLDLTheearlylesion:modifiedlipoproteinsandfoamcellformationClassesofScavengerReceptorsTheScavengerReceptorFamilies formodifiedLDL/ThemacrophageasaninflammatorymediatorStatinsinducePPARαactivityMacrophages T-lymphocytes InflammationRoleofmacrophagesTLRreceptorsandatherosclerosisImmuno-responseReducedatherosclerosisinMyD88nullmiceTLRsandatherosclerosis///WhydoesoxidizedLDLbecomeimmunogenic?/HowDoesImmunizationWithOxidizedLDLAffectAtherosclerosis?Isitpossibletoproduceavaccineagainstatherosclerosis?CharacterizationofepitopesinoxidizedLDLbyalibraryofpeptideELISAsActiveimmunizationofapoEnullmicewithapoB-100peptidesequencesEffectofoxidizedLDLpeptidevaccinesonatherosclerosisinmiceEffectofimmunizationwithMDA-apoB-100peptide45onspecificIgM,IgG,IgG1(Th2)andIgG2a(Th1)inapoEnullmiceImmunizationusingMDA-apoB-100peptidesinmicePassiveimmunizationstrategyEffectofpassiveimmunizationwithrecombinanthumanIgGagainstpeptide45onearlyatherosclerosisinmiceRegressionofaorticplaqueareainantibodytreatedApobec-1-/-/LDLr-/-miceRecombinanthumanantibodiestoMDA-apoB-100peptidesupregulateABCA-1expressioninvivoandinvitroRecombinanthumanantibodiestoMDA-apoB-100peptidesblockoxidi