Purpose:Themultifactorialpathogenesisofcoronaryatheroscleroticlesionformationhasbeeninvestigatedinaswinemodelofhighcholesteroldietinducdatherogenesisanddataprocessedbyasystemsapproach.Methods:Farmpigswerefedonstandardorhighcholesteroldietof8and16weeksduration.Plasmaassessmentoftotalcholesterol,HDL,LDL,andELISAofsomecytokinesandICAM-1wereperformedonbaselineandend-dietsamples.Segmentsoftherightcoronaryarterywereincubatedfor24hinserum-freemediumtocollectsecretedproteinsandtheirexpressionanalyzedbymassspectrometry.Dataofplasmaandtissuefactorswereprocessedbyastatisticalsystemsinferenceapproach:bothhistologicparametersofcoronaryintimalthickness(IT)andoflesionarea(LA)werechosenasdependentvariables(coronaryatheroscleroticburden).Results:Relationsamongplasmaadhesionmolecules,cytokines,lipoproteins,tissueproteinsandhistologyindexeswereintegratedinamodelregressionscheme.Bayesianmodelaveraging(BMA)variableselectionwaschosenasamethodtoidentifyrelevantfactorsassociatedtoatheroscleroticburden:TNFαwasidentifiedasanassociatedplasmamarker,oxLDLandHDLasrelevantlipoproteins;macrophagefunctionrelatedantioxidantCatalaseenzyme,lysosomeassociatedCathepsinD,S100-A10,andTransforminggrowthfactor-beta-inducedproteinig-h3wereidentifiedandselectedasassociatedtoatherogenesisoutcome.Conclusions:Theresultsofthissystemsapproachareconsistentwiththehypothesisthat,inhighcholesteroldiet-inducedexperimentalatherogenesis,theinteractionbetweenplasmacytokines,lipoproteinsandartery-specificproteins,influenceslesioninitiationandgrowth.Inparticular,somemacrophagefunctionrelatedproteinsarefoundsignificantlyandpositivelyassociatedtoatheroscleroticburden,suggestinganovelmolecularframeworkintotheatherogenesis-inflammatorydisorder.
Inflammation blood and tissue factors of plaque growth in an experimental model evidenced by a systems approach
CECCHETTINI, ANTONELLA;
2014-01-01
Abstract
Purpose:Themultifactorialpathogenesisofcoronaryatheroscleroticlesionformationhasbeeninvestigatedinaswinemodelofhighcholesteroldietinducdatherogenesisanddataprocessedbyasystemsapproach.Methods:Farmpigswerefedonstandardorhighcholesteroldietof8and16weeksduration.Plasmaassessmentoftotalcholesterol,HDL,LDL,andELISAofsomecytokinesandICAM-1wereperformedonbaselineandend-dietsamples.Segmentsoftherightcoronaryarterywereincubatedfor24hinserum-freemediumtocollectsecretedproteinsandtheirexpressionanalyzedbymassspectrometry.Dataofplasmaandtissuefactorswereprocessedbyastatisticalsystemsinferenceapproach:bothhistologicparametersofcoronaryintimalthickness(IT)andoflesionarea(LA)werechosenasdependentvariables(coronaryatheroscleroticburden).Results:Relationsamongplasmaadhesionmolecules,cytokines,lipoproteins,tissueproteinsandhistologyindexeswereintegratedinamodelregressionscheme.Bayesianmodelaveraging(BMA)variableselectionwaschosenasamethodtoidentifyrelevantfactorsassociatedtoatheroscleroticburden:TNFαwasidentifiedasanassociatedplasmamarker,oxLDLandHDLasrelevantlipoproteins;macrophagefunctionrelatedantioxidantCatalaseenzyme,lysosomeassociatedCathepsinD,S100-A10,andTransforminggrowthfactor-beta-inducedproteinig-h3wereidentifiedandselectedasassociatedtoatherogenesisoutcome.Conclusions:Theresultsofthissystemsapproachareconsistentwiththehypothesisthat,inhighcholesteroldiet-inducedexperimentalatherogenesis,theinteractionbetweenplasmacytokines,lipoproteinsandartery-specificproteins,influenceslesioninitiationandgrowth.Inparticular,somemacrophagefunctionrelatedproteinsarefoundsignificantlyandpositivelyassociatedtoatheroscleroticburden,suggestinganovelmolecularframeworkintotheatherogenesis-inflammatorydisorder.File | Dimensione | Formato | |
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