Chronic Over-Expression of Heat Shock Protein 27 Attenuates Atherogenesis and Enhances Plaque Remodeling A Combined Histological and Mechanical Assessment of Aortic Lesions.docVIP

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Chronic Over-Expression of Heat Shock Protein 27 Attenuates Atherogenesis and Enhances Plaque Remodeling A Combined Histological and Mechanical Assessment of Aortic Lesions.doc

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Chronic Over-Expression of Heat Shock Protein 27 Attenuates Atherogenesis and Enhances Plaque Remodeling A Combined Histological and Mechanical Assessment of Aortic Lesions

ChronicOver-ExpressionofHeatShockProtein27 AttenuatesAtherogenesisandEnhancesPlaque Remodeling:ACombinedHistologicalandMechanical AssessmentofAorticLesions CharlesM.Cuerrier1,2.,Yong-XiangChen1.,DominiqueTremblay2,KateyRayner1,MelissaMcNulty1, XiaoLingZhao1,ChristopherR.J.Kennedy3,JacquelinedeBelleRoche4,AndrewE.Pelling2,5,6, EdwardR.O’Brien1,7 * 1University of Ottawa Heart Institute, Ottawa, Canada, 2Centre for Interdisciplinary NanoPhysics, Department of Physics, University of Ottawa, Ottawa, Canada, 3DepartmentsofMedicineandCellularandMolecularMedicine,UniversityofOttawa,Ottawa,Canada,4ImperialCollege,London,UnitedKingdom,5Departmentof Biology,UniversityofOttawa,Ottawa,Canada,6InstituteforScience,SocietyandPolicy,UniversityofOttawa,Ottawa,Canada,7LibinCardiovascularInstituteofAlberta, Calgary,Canada Abstract Aims:ExpressionofHeatShockProtein-27(HSP27)isreducedinhumancoronaryatherosclerosis.Over-expressionofHSP27 is protective against the early formation of lesions in atherosclerosis-prone apoE2/2 mice (apoE2/2HSP27o/e) - however, only in females. We now seek to determine if chronic HSP27 over-expression is protective in a model of advanced atherosclerosisinbothmaleandfemaleapoE2/2 mice. MethodsandResults:After12weeksonahighfatdiet,serumHSP27levelsrosemorethan16-foldinmaleandfemale apoE2/2HSP27o/emice,althoughfemaleshadhigherlevelsthanmales.RelativetoapoE2/2mice,femaleapoE2/2HSP27o/e miceshowedreductionsinaorticlesionareaof35%forenfaceand30%forcross-sectionalsinustissuesections–withthe same parameters reduced by 21% and 24% in male cohorts; respectively. Aortic plaques from apoE2/2HSP27o/e mice showedalmost50%reductionsintheareaoccupiedbycholesterolcleftsandfreecholesterol,withfewermacrophagesand reduced apoptosis but greater intimal smooth muscle cell and collagen content. The analysis of the aortic mechanical propertiesshowedincreasedvesselstiffnessinapoE2/2HSP27o/emice(41%infemale,34%inmale)comparetoapoE2/2 counterparts. Conclusions:Chronicover-expressionofHS