Abstract
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Objective: Infusions ofapoA-Iinthelipid-freeformorasaconstituentofdiscoidalreconstitutedhigh-density lipoproteins,(A-I)rHDL,markedlyinhibitacutevascularinflammationinnormocholesterolemic New ZealandWhite(NZW)rabbits.ThiseffectisapparentevenwhenapoA-Iisadministered24hpriorto the inflammatoryinsult.Thepresentstudyasksifthisbenefitisrelatedtoanimprovedanti-inflammatory capacity of thehigh-densitylipoprotein(HDL)fraction,ortoincreasedarterialexpressionofgenesthat inhibit inflammation.
Methods andresults: The abilityofapoA-Itoincreasetheanti-inflammatorycapacityofHDLwasassessed by infusingnormocholesterolemicNZWrabbitswithsaline,lipid-freeapoA-Ior(A-I)rHDL.Theinfused apoA-I incorporatedrapidlyintotherabbitHDLfraction.Theanimalsweresacrificedat5or360minpost-infusion andplasmawascollected.HDLwereisolatedbyultracentrifugationandincubatedwithcytokine-activated culturedhumancoronaryarteryendothelialcells.HDLfromanimalssacrificedat5minpost-apoA-I infusionhadaslightlyenhancedanti-inflammatorycapacityrelativetoHDLfromthesaline- infused animals.Theanti-inflammatorycapacityofHDLfromtheanimalssacrificedat360minpost- apoA-I infusionwascomparabletothatofHDLfromthesaline-infusedanimals.Theeffectof(A-I)rHDL infusions onarterial3-hydroxysteroid-24 reductase(DHCR24)andendothelialadhesionmolecule expression wasinvestigatedincholesterol-fedNZWrabbits.Relativetoanimalsinfusedwithsaline,(A- I)rHDL infusionsdecreasedaorticVCAM-1andICAM-1proteinexpressionby73and54%,respectively (p < 0.05),andincreasedDHCR24mRNAlevelsby56%(p < 0.0001).