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

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.
G., Pelosi; S., Rocchiccioli; Cecchettini, Antonella; F., Viglione; M., Puntoni; O., Parodi; E., Capobianco; M. G., Trivella
File in questo prodotto:
File Dimensione Formato  
Frontiers in genetics 2014.pdf

accesso aperto

Tipologia: Versione finale editoriale
Licenza: Creative commons
Dimensione 1.13 MB
Formato Adobe PDF
1.13 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/435078
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 4
social impact