InterplayamongH3K9-editingenzymesSUV39H1,JMJD2CandSRC-1drivesp66ShctranscriptionandvascularoxidativestressinobesitySarahCostantino1,2†,FrancescoPaneni1,2†,AgostinoVirdis3,ShafaatHussain1,ShafeeqAhmedMohammed1,2,GiulianaCapretti4,AlexanderAkhmedov2,KevinDalgaard5,SergioChiandotto4,J.AndrewPospisilik5,ThomasJenuwein5,MarcoGiorgio6,MassimoVolpe4,7,StefanoTaddei3,ThomasF.Lu¨scher2,andFrancescoCosentino1*1CardiologyUnit,DepartmentofMedicineSolna,KarolinskaInstituteandKarolinskaUniversityHospital,Solnava¨gen,17176Stockholm,Sweden;2CenterforMolecularCardiology,UniversityofZu¨rich,Wagistrasse12,8952Schlieren,Switzerland;3DepartmentofClinicalandExperimentalMedicine,UniversityofPisa,56121Pisa,Italy;4Cardiology,DepartmentofClinicalandMolecularMedicine,UniversityofRomeSapienza,ViadiGrottarossa,1035,00189Rome,Italy;5DepartmentofEpigenetics,MaxPlanckInstituteofImmunology,Stuebeweg51,Freiburg79108,Germany;6DepartmentofExperimentalOncology,InstituteofOncology,ViaAdamello16,20139Milano,Italy;and7DepartmentofAngio–Cardio–Neurology,IRCCSNeuromed,Pozzilli,ItalyReceived8April2017;revised19June2017;editorialdecision4October2017;accepted10October2017ThispaperwasguesteditedbyAnthonyN.DeMaria,MD(ademaria@ucsd.edu).AimsAccumulationofreactiveoxygenspecies(ROS)promotesvasculardiseaseinobesity,buttheunderlyingmolecularmechanismsremainpoorlyunderstood.Theadaptorp66ShcisemergingasakeymoleculeresponsibleforROSgenerationandvasculardamage.Thisstudyinvestigateswhetherepigeneticregulationofp66Shccontributestoobesity-relatedvasculardisease....................................................................................................................................................................................................MethodsandresultsROS-drivenendothelialdysfunctionwasobservedinvisceralfatarteries(VFAs)isolatedfromobesesubjectswhencom-paredwithnormalweightcontrols.Geneprofilingofchromatin-modifyingenzymesinVFArevealedasignificantdysre-gulationofmethyltransferaseSUV39H1(foldchang...
