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201AABCA-1.
SeeATP-bindingcassetteproteinA1ABCG1receptor,84,86transportereNOSactivity,807-ketocholesterol(KC)level,80–81ABCtransportersatherosclerosis,79cholesteroleffluxpathways,79endothelialfunction,80Abetalipoproteinemia,9Amyloidosis,humanapoA-Imutations,67–68Anacetrapib,168,169APOA1/C3/A4/A5gene,116–117ApolipoproteinA-I(ApoA-I),5–6ABCA1-apoA-I/preb-HDLpathway,175deficiency,familialapoAI/CIII/AIVgenedefectscodon84nonsensemutation,56cornealarcus,56fatsolublevitaminslevels,60HDLparticlesandsubpopulations,58,59heterozygotesvs.
homozygotes,58ischemiaandcalciumdeposition,57planarxanthomas,55–56Q[-2]Xmutation,56tuboeruptivexanthomas,57vitaminKdeficiency,55ERASEtrial,176ethanolintakeeffectsHDLincreasesmechanisms,131–132HDLsubfractions,content,131levels,131geneticmutationsgeneregulation,cellculturesandanimalmodels,20–22invivoregulation,transgenicmice,22–23lecithin:cholesterolacyltransferase(LCAT),20,21IVUSparameterschanges,175Milano,174mutantshereditaryamyloidosis,67–68low-HDLphenotype,63–67promoter,141REVERSALtrial,176statinsdose-effectof,151,152kinetics,153metabolismof,153productionrate(PR),151–154transcriptionalregulationnuclearreceptors,cellcultures,15transgenicmice,15–19ApolipoproteinA-II(ApoA-II),6ApolipoproteinA-IV(ApoA-IV),6–7ApolipoproteinA-V(ApoA-V),7ApolipoproteinB-48(ApoB-48),7ApolipoproteinB-100(ApoB-100),7ApolipoproteinE(ApoE),7Atherogenicity,CETP,98,99Atheroprotection,apoA-Imutants,66–67Atherosclerosis,49–50ABCA1-mediatedcholesterolefflux,91,92cIMT,90–91FLDandFEDcarriers,91,92ATP-bindingcassetteproteinA1(ABCA-1)gene,116–117mediatedcellularcholesterolefflux,165receptor,86,87transporter,Tangierdisease,75BBiosynthesispathway,cholesterol,151–152CCapolipoproteins(ApoC-I),7Carotidintima-mediathickness(cIMT),64–65,91–92,176Cerebrotendinousxanthomatosis,2CETP.
SeeCholesterylestertransferproteinCholesterolabsorption,3biosynthesispathway,151–152metabolismABCG1,84SR-BI,103–104production,1–2Cholesteroleffluxcellcholesterolhomeostasis,83cellcholesterolmasslabeledcholesterol,85–86mobilizationandtransporterexpression,86netflux,84–85pathways,ABCtransporters,79RCTprocess,83andreversecholesteroltransport,174serumABCA1transporter,83–84ABCG1transporter,84componentactivities,83Index202IndexCholesterolefflux(cont.
)efficiency,84HDL-CandLDL-Cconcentration,85J774cells,84,85radioactivemeasurement,cells,83SR-BIreceptor,84transferpathway,84Cholesterylester(CE)flux,83Cholesterylestertransferprotein(CETP),103,133,147action,121atherogenicitymutationsandpolymorphisms,CHD,98triglyceride(TG)metabolism,98crystalstructure,ribbonmodel,167deficiencygenetics,96–97phenotype,97–98developmentofanacetrapib,169dalcetrapib,167–168torcetrapib,168–169vaccine,167gene,116–118geneticvariationandCHDrisk,Taq1B,165inhibitordevelopmentApoB-containinglipoproteins,99cholesterolefflux,99torcetrapib,98–99lipoproteintriglyceridehydrolysis,166mechanismfor,167statinseffects,151–154structureandfunction,95,96,168Chylomicrons,7–9,121–123cIMT.
SeeCarotidintima-mediathicknessConjugatedequineestrogen(CEE),141Coronaryheartdisease(CHD)ABCA1transporterfunction,defective,75cholesterylestertransferproteindeficiency,98familialapoAI/CIII/AIVgenedefects,55–60andgeneticvariation,Taq1B,165lipoproteinassessment,riskcardiaccalciumimages,188CTangiographicimages,187,189non-calcifiedandcalcifiedcoronaryplaques,188mutationsandpolymorphisms,98precipitationmethods,relativerisk,185COS-1,LCATmutants,90DDalcetrapib,168–169Docosahexaenoicacid(DHA),4,121Dysbetalipoproteinemia,10Dyslipidemia,146EEffectofrHDLonatherosclerosis-safetyandefficacy(ERASE)trial,176Eicosapentaenoicacid(EPA),121Endotheliallipase(EL),133ERASE.
SeeEffectofrHDLonatherosclerosis-safetyandefficacytrialEstrogeneffectsadministrationroutes,139apoA-Igene,142apoA-Imetabolism,140–14117b-estradiol,140CETP,140conjugatedequineestrogen,141ethinylestradiol,140–141FSHsecretion,139high-densitylipoproteincholesterol(HDL-C),139–140proteinsrole,140receptors(ER),141–142scavengerreceptorclassBtypeI,140Ethanolintakeeffectsatherosclerosis,133–134beveragetype,129compositionandconcentrationapolipoproteinlevels,131apolipoproteinturnover,131–132lipidcontent,131proteinlevels,131sizesubfractions,130–131doseandpatternofintake,129–130geneticmodulation,134–135metabolismandfunctionCETP,133EL,133HL,133LCAT,132–133LPL,133PLTP,133FFamilialcombinedhyperlipidemia,2–3Familialdyslipidemia,12,190Familialhypercholesterolemia,12,13FamilialLCATdeficiency(FLD),90–92Fattyacids,4–5Fisheyedisease(FED),90–92Fishoilsupplementation,kineticseffects,160Framinghamriskassessment,189Freecholesterol(FC)flux,83GGALNT2gene,118–119GeneticLCATdeficiencyatherosclerosisABCA1-mediatedcholesterolefflux,91,92cIMT,90–91FLDandFEDcarriers,91,92LCATgene,89lipid/lipoproteinphenotypeconcentrationandactivity,90FLDandFEDcarriers,90–91sequenceanalysis,89observation,92,93Geneticlocirole,plasmaHDL-CABCA1gene,116–117APOA1/C3/A4/A5gene,116–117CETPgene,116–118GALNT2gene,118–119LCATgene,116–118LIPCgene,116–118LIPGgene,116–118LPLgene,116–118multiplecohortGWAS,113–116PLTPgene,116–118203IndexsinglecohortGWAScardiovasculardisease(CVD),113family-basedassociationtests(FBAT),111generalizedestimatingequations(GEE),111WGHScohort,112Geneticmutations,apoA-Igenegeneregulation,cellculturesandanimalmodels,20–22invivoregulation,transgenicmiceFPLCanalysis,22lipoproteinlipase(LPL),22–23phospholipidtransferprotein(PLTP),22–23lecithin:cholesterolacyltransferase(LCAT),20,21Genome-wideassociationstudies(GWAS).
SeealsoGeneticlocirole,plasmaHDL-Cmultiplecohorts,HDLcholesterol,113–116singlecohort,HDLcholesterol,111–113GREekAtorvastatinandCoronaryheartdiseaseEvaluation(GREACE)study,151,HHepaticlipase(HL),133Hepatocytenuclearfactor-4(HNF-4),15–20Highdensitylipoprotein(HDL)anti-inflammatorypropertiesinvitrostudies,50–51invivostudies,51apolipoproteinA-ImutantsA-IM,63atherosclerosisprotection,66–67carotidintima-mediathickness(cIMT),64–65cellcholesterolefflux,65missense-nonsensemutations,64atherosclerosis,49–50cardioprotectiveproperties,48–49cholesterylestertransferproteinatherogenicity,98deficiency,geneticsandphenotype,96–98inhibitordevelopment,98–99structureandfunction,95,96clinicalrelevance,biology,81endothelialfunctionbeneficialeffectsof,79eNOSactivity,80familialapoAI/CIII/AIVgenedefects,55–60heterogeneity,45–46inflammation,50infusiontherapy,apoA-IABCA1-apoA-I/preb-HDLpathway,175CETP,174ERASEtrial,176IVUSparameterschanges,175REVERSALtrial,176mimeticpeptidesD-4F,177ETC642,176LSI-518P,177NIH5A,177originsandstructure,45remodellingandatherogenesisrelationship,46–48Highdensitylipoprotein-cholesterol(HDL-C),173ABCG1-mediatedcholesterolefflux,37apoA-Isynthesis,34–35catabolism,41–42cellularcholesterolefflux,ABCA1,35CETPcycle,37–39cholesterolesterification,LCAT,35–36distinctparticles,33geneticlocirole(seeGeneticlocirole,plasmaHDL-C)HL-mediatedlypolyses,39–40innateimmunity,33metabolismCETP,95–100CETPinhibition,165–169estrogen,139–142ethanolintakeeffects,129–135niacin,145–148nutritionalandlifestylefactors,121–126statins,151–154proteomics2DPAGEmethodology,30G-force,29highsaltconcentration,29hydrophobicforcesandanchorproteins,31physiologicalfunctions,29SRBIcycle,40statinsdose-effectof,151,152metabolismof,153structureABCA1pathway,27apoA-I,27CETPactivity,27–28hypertriglyceridemia,27lecithincholesterylacyltransferase(LCAT),27physico–chemicalstructure,workingtheory,27PPARa,28scavengerreceptorB1(SRB1),28serumamyloidA,27sPLA2andEL,synergisticeffect,28statins,27–28subclassesseparationelectrophoreticmobility,25immunoblottingandimage-analysis,26non-denaturingpolyarcrylamidegelelectrophoresis(ndPAGE),25sizeexclusionchromatography,25Hormoneresponseelements(HREs),15–193-Hydroxy-3-methylglutarylcoenzymeA(HMGCoA)reductase,151,152,154Hyperalphalipoproteinemia(HALP),99Hypertriglyceridemia,9–10,27Hypobetalipoproteinemia,9IIncrementalDecreaseinEndpointsthroughAggressiveLipidlowering(IDEAL)study,154Inhibitordevelopment,CETPanacetrapib,169dalcetrapibchemicalstructureof,168dal-OUTCOMES,168JTT-705,167torcetrapibchemicalstructureof,168nonproductivecomplex,168posthocanalysis,169vaccine,167Intermediatedensitylipoproteins(IDL),182204IndexK7-Ketocholesterol(KC),80–81Kineticdefects,apoAandapoBtransport,158LLecithin:cholesterolacyltransferase(LCAT)atherosclerosis,91–92cholesterolesterification,35–36deficiencysyndromesfamilialLCATdeficiency(FLD),89–92fish-eyedisease(FED),89–92ethanolintakeeffects,132–133gene,116–118genemutations(seeGeneticLCATdeficiency)lipid/lipoproteinphenotype,89–91plasmalipids,4Lifestyleanddruginterventions,kineticseffects,160LIPCgene,116–118LIPGgene,116–118Lipid/lipoproteinphenotypeconcentrationandactivity,90FLDandFEDcarriers,90–91sequenceanalysis,89Lipoproteinassessmentapolipoproteinsimmunoassays,185Lp(a),186totalcholesterol,comparisonof,186CHDriskcardiaccalciumimages,188CTangiographicimages,187,189non-calcifiedandcalcifiedcoronaryplaques,188dietandlifestylemodification,191Framinghamriskassessment,189geneticforms,HDLdeficiency,190–191gradientgelelectrophoresis,183hyperlipoproteinemiatypes,181inflammatorymarkersCRPandLpPLA,186JUPITERtrial,187INTERHEARTexperience,190lipidabnormalities,secondarycauses,19023lipidtrials,meta-analysisof,194nuclearmagneticresonance,183–184pharmacologicagentsanionexchangeresins,193ezetimibe,193fibrates,191–192fishoilcapsules,193–194niacin,192–193statins,191plasmalipoproteins,182polypill,190precipitationmethodsapolipoproteinB,184Friedewaldformula,185relativerisk,CHD,185statins,185ReynoldsriskscoreandPROCAMriskprediction,189–190ultracentrifugation,182Lipoproteinlipase(LPL)gene,116–118geneticloci,115–116hydrolysis,36metabolismandfunction,133Lipoprotein(a)Lp(a),12–13,186,195Lowdensitylipoproteins(LDL),12MMedroxyprogesteroneacetate,141Membrane-boundestrogenreceptors,142Metabolicsyndrome,HDLtransportcombinationtherapy,fenofibratevs.
rosuvastatin,161–162interventionstudiesfishoilsupplementation,160weightloss,160tracerkineticsadiponectin,159apoAandapoBtransport,158HDL-apoA-Ifractionalcatabolicrate,158–159plasmatriglyceride,apoC-III,159PRvs.
FCR,HDL-apoA-I,159Mitogen-activatedproteinkinase,141–142NNationalCholesterolEducationProgram,125Niacineffectsadipocyte,145,146CETPactivity,147–148dyslipidemia,146GPR109Areceptors,145HDL-C-raisingmedication,145HDLmetabolismandsubfractions,146humanhepatomacelllineHepG2,147normolipidemicwomen,145,146VLDL,145Niemann–PickC1-like1protein(NPC1L1)trasporter,121Non-denaturingpolyarcrylamidegelelectrophoresis(ndPAGE),25NutritionalandlifestylefactorsATP-bindingcassette(ABC)transporter,122carbohydrateseffectscontrolchowdiets,animalstudies,125kineticstudies,humans,125Westerndiet,125cholesterolabsorption,121,122cholesterolsynthesis,121,122dietarycholesteroleffects,121,124EPAandDHA,122fattyacideffectsdietarytrials,124omega-3fattyacidseffects,HDL,125omega6polyunsaturatedfattyacids,124exercise,effectsof,126HDLparticlemetabolism,124model,123linoleicacidconversion,121,122lipoproteinmetabolism,123Niemann–PickC1-like1protein(NPC1L1)transporter,122optimallifestyleanddietgoals,126restricteddiet,cholesterolandsaturatedfat,125weightlosseffect,126PPeroxisomeproliferator-activatedreceptor-a(PPAR-a),agonistsfenofibrate,159,161–162rosuvastatin,161–162statins,161205IndexPhospholipids,4Phospholipidtransferprotein(PLTP)ethanolintake,133gene,116–118HDLremodellingof,48Phytosterolemia,4Plasmalipids,4Plasmalipoproteins,7ProspectiveCardiovascularMuenster(PROCAM)study,189RReversalofatherosclerosiswithaggressivelipidlowering(REVERSAL)trial,176Reversecholesteroltransport(RCT)cholesterylestertransferproteindeficiency,97–99ethanoleffects,133–134process,83SScavengerreceptorB1(SRB1),28,140adrenalphysiology,105atherosclerosis,105CETP,103cholesterolmass,83,84,86,87CLA-1transgene,106endothelialfunctions,104HDLcholesterolmetabolism,103–104hepaticexpression,104humanSCARB1genechromosomalmapping,106genevariation,106mediatedcholesterolefflux,165microbialpathogens,105PDZK1-dependentregulationadaptorprotein,106KOmice,cholesteroldiet,106tissue-specificphenomenon,105role,103,104signaling,104Sizeexclusionchromatography,25SR-BI.
SeeScavengerreceptorB1(SRB1)Statinseffects,HDLmetabolismA-Ifractionalcatabolicrate(FCR),151–153apoA-I,151–153CETP,151–153cholesterolbiosynthesispathway,151–152dose-effectof,151–152GREACEstudy,151HDL-C,151–154HMG-CoA,151,152,154IDEALstudy,154STELLARstudy,151Sterolregulatoryelement-bindingprotein(SREBP),151TTangierdisease,35ABCA1transporterfunction,defectiveCHDriskreduction,75overexpressiondefects,75clinicalfeatures,71–73island,71,72lipoproteinmetabolismapoA-Ideficiency,75betacarotenelevel,74hypertriglyceridemia,73plasmadecaycurves,74pathologicfindings,71,73Therapeuticregulation,HDLtransport.
SeealsoMetabolicsyndrome,HDLtransportkineticseffects,metabolicsyndromefishoilsupplementation,160weightloss,160metabolicsyndrome,tracerkineticsadiponectin,159apoAandapoBtransport,158HDL-apoA-Ifractionalcatabolicrate,158–159plasmatriglyceride,apoC-III,159PRvs.
FCR,HDL-apoA-I,159PPAR-aagonistsfenofibrate,159,161–162rosuvastatin,161–162statins,161tracermethodsprinciplesHDL-apoAkineticstudy,157–158transportrates,158Torcetrapib,49,98–99,168–169Transcriptionalregulation,apoA-Igenenuclearreceptors,SP1andenhancer,cellcultures,15transgenicmiceapoCIIIenhancer,17–18HRE,16–17synergisticinteraction,19WTapoA-Iconstruct,18Triglyceride-richlipoprotein(TRL),124–126VVerylowdensitylipoprotein(VLDL),11,97–99,145VeteransAffairsHighDensityLipoproteinInterventionTrial(VA-HIT),49,126VitaminKdeficiency,apoA-I,55WWeightloss,kineticseffects,160WesternandPaigen-diet,105,106Women'sGenomeHealthStudy(WGHS)cohort,112
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