新治疗目标：HDL PPT课件.ppt

《新治疗目标：HDL PPT课件.ppt》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、HDLasaTherapeuticTargetDanielJ.Rader,M.D.100160220RiskofCHDLowHDL-CisanIndependentPredictorofCHDRiskEvenWhenLDL-CisLowHDL-C(mg/dL)LDL-C(mg/dL)25GordonTetal.AmJMed1977;62:707-714.456585ATPIII:NewDefinitionofLowHDL-CExpertPanelonDetection,Evaluation,a

2、ndTreatmentofHighBloodCholesterolinAdults.JAMA2001;285:2486-2497.LowHDL-Cwasredefinedas<40mg/dLATPIII:TheMetabolicSyndromeDiagnosisisestablishedwhen3oftheseriskfactorsarepresent.ExpertPanelonDetection,Evaluation,andTreatmentofHighBloodCholesterolinA

3、dults.JAMA2001;285:2486-2497.RiskFactorDefiningLevelAbdominalobesity(Waistcircumference)MenWomen>102cm(>40in)>88cm(>35in)TG150mg/dLHDL-CMenWomen<40mg/dL<50mg/dLBloodpressure130/85mmHgFastingglucose110mg/dLIsHDL-CSimplyaMarkerofIncreasedCardio

4、vascularRisk?SmokeAresedentaryAreobeseAreinsulinresistantordiabeticHavehypertriglyceridemiaHavechronicinflammatorydisordersLowHDL-Clevelsarecommonlyfoundinpatientswho:ProductionofApoA-IbyLiverandIntestineA-IA-IILiverIntestineHDLA-IHDLReducedinitiatio

5、nandprogressionofatherosclerosisintransgenicmiceandrabbitsRegressionofpre-existingatherosclerosisinanimalsIncreasedApoA-IProductionisAntiatherogenicinAnimalsIncreaseapoA-IproductionPromotereversecholesteroltransportDelaycatabolismofHDLHDLMetabolismas

6、aTherapeuticTarget:PotentialStrategiesSmallmoleculeupregulationofapoA-IgenetranscriptionIntravenousinfusionofrecombinantprotein(wild-typeapoA-I,apoA-IMilano)AdministrationofpeptidesbasedonapoA-IsequenceSomaticgenetransferofapoA-IDNA(liver,intestine,m

7、uscle,hematopoeticcells)ApproachestoIncreasingApoA-IProductionIncreaseapoA-IproductionPromotereversecholesteroltransportDelaycatabolismofHDLHDLasaTherapeuticTarget:PotentialStrategiesA-IHDLandReverseCholesterolTransportLiverCECEFCLCATFCBileSR-BIABCA1

8、MacrophageMatureHDLNascentHDLA-IFCCEFCRegulationofCholesterolEffluxintheMacrophageFCFCoxysterolsLXR/RXRABCA1PPARsA-IPharmacologicManipulationofCholesterolEffluxLXR/RXRPPARsFibrates,TZDs,newagentsNewagentsA-IFCABCA1IncreaseapoA-IproductionPromoterev