Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure 英文参考文献.docVIP
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Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure 英文参考文献
DifferentFactorsAffectingHumanANPAmyloid
AggregationandTheirImplicationsinCongestiveHeart
Failure
LiaMillucci1,EugenioPaccagnini2,LorenzoGhezzi1,GiuliaBernardini1,DanielaBraconi1 ,Marcella
Laschi1,MarcoConsumi3,AdrianoSpreafico4,PieroTanganelli5,PietroLupetti2,AgneseMagnani3,
AnnalisaSantucci1*
1Dipartimento di Biotecnologie, Universita` degli Studi di Siena, Siena, Italy, 2Dipartimento di Biologia Evolutiva, Universita` degli Studi di Siena, Siena, Italy,
3DipartimentoFarmacoChimicoTecnologico,Universita` degliStudidiSiena,Siena,Italy,4DipartimentodiMedicinaClinicaeScienzeImmunologiche,Universita` degli
StudidiSiena,Siena,Italy,5DipartimentodiPatologiaUmanaeOncologia,Universita` degliStudidiSiena,Siena,Italy
Abstract
Aims:AtrialNatriureticPeptide(ANP)-containingamyloidisfrequentlyfoundintheelderlyheart.Nodataexistregarding
ANPaggregationprocessanditslinktopathologies.Ouraimswere:i)toexperimentallyprovethepresumptiveassociation
of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby
elucidatingIAAimplicationintheCHFpathogenesis.
MethodsandResults:Asignificantprevalence(85%)ofIAAwasimmunohistochemicallyprovenexvivoinbiopsiesfrom
CHFpatients.Weinvestigatedinvitro(usingCongoRed,ThioflavinT,SDS,transmissionelectronmicroscopy,infrared
spectroscopy)ANPfibrillogenesis,startingfroma-ANPaswellastheabilityofdimericb-ANPtopromoteamyloidformation.
Different conditions were adopted, including those reproducing b-ANP prevalence in CHF. Our results defined the
uncommon rapidity of a-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the
onsetofafibrillizationprocesssubsequentlyproceedingatphysiologicalpH.Interestingly,CHF-likeconditionsinducedthe
productionofthemoststableandtime-resistantANPfibrilssuggestingthatCHFaffectedpeoplemaybepronetodevelop
IAA.
Conclusions:WeestablishedalinkbetweenIAAandCHFbyexvivoexaminationandassessedthatb-ANPis,invitro,the
seedofANPfibrils
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