Mechanical load‐dependent cardiac ER stress in vitro and in vivo: Effects of preload and afterload

摘要

Proteinsarefoldedintheendoplasmicreticulum(ER).ERstressinitiallyleadstocompensatoryupregulationofERchaperonesandlatertoapoptosis,butthecontributionofbiomechanicalloadvs.neurohumoralstresstomyocardialERstressisunknown.WeshowthattheERchaperonesGrp78andcalreticulin(CRT)areupregulatedbyafterload,butnotbypreloadinvitroandinvivo.AngiotensinIIupregulatedERchaperonesinunloadedmusclestrips,buttheangiotensinreceptor‐1antagonistirbesartandidnotsignificantlyblunttheinductionofERchaperonesbyafterload.Inmonocrotaline‐treatedrats,Grp78andCRTwereupregulatedintheafterloadedrightventricle,butnotintheonlyneurohumorallystressedleftventricle.ThesefindingssuggestthatafterloadbutnotpreloadinducesmyocardialERstress,largelyindependentofangiotensinIIsignaling...