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《MicroRNA-328 Contributes to Adverse ElectricaRemodeling in Atrial FibrillationlMICRORAN-328有助于不利的电气 心房颤动重构》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、MicroRNA-328ContributestoAdverseElectricalRemodelinginAtrialFibrillationYanjieLu,MD,PhD*;YingZhang,MD,PhD*;NingWang,MD,PhD;ZhenweiPan,MD,PhD;XuGao,MD,PhD;FengminZhang,MD,PhD;YongZhang,MD,PhD;HongliShan,MD,PhD;XiaobinLuo,MSc;YunlongBai,MD,PhD;LihuaSun,MD,PhD;WuqiSong,MD,PhD;ChaoqianXu,MD
2、,PhD;ZhiguoWang,PhD;BaofengYang,MD,PhDBackground—Acharacteristicofbothclinicalandexperimentalatrialfibrillation(AF)isatrialelectricremodeling2associatedwithprofoundreductionofL-typeCacurrentandshorteningoftheactionpotentialduration.ThepossibilitythatmicroRNAs(miRNAs)maybeinvolvedinthis
3、processhasnotbeentested.Accordingly,weassessedthepotentialroleofmiRNAsinregulatingexperimentalAF.MethodsandResults—ThemiRNAtranscriptomewasanalyzedbymicroarrayandverifiedbyreal-timereverse-transcriptionpolymerasechainreactionwithleftatrialsamplesfromdogswithAFestablishedbyrightatrialtac
4、hypacingfor8weeksandfromhumanatrialsamplesfromAFpatientswithrheumaticheartdisease.miR-223,miR-328,andmiR-664werefoundtobeupregulatedby2fold,whereasmiR-101,miR-320,andmiR-499weredownregulatedbyatleast50%.Inparticular,miR-328levelwaselevatedby3.9-foldinAFdogsand3.5-foldinAFpatientsrelati
5、vetonon-AFsubjects.ComputationalpredictionidentifiedCACNA1CandCACNB1,whichencode2cardiacL-typeCachannel1c-and1subunits,respectively,aspotentialtargetsformiR-328.ForcedexpressionofmiR-328throughadenovirusinfectionincanineatriumandtransgenicapproachinmicerecapitulatedthephenotypes2ofA
6、F,exemplifiedbyenhancedAFvulnerability,diminishedL-typeCacurrent,andshortenedatrialactionpotentialduration.NormalizationofmiR-328levelwithantagomiRreversedtheconditions,andgeneticknockdownofendogenousmiR-328dampenedAFvulnerability.CACNA1CandCACNB1asthecognatetargetgenesformiR-328werecon
7、firmedbyWesternblotandluciferaseactivityassayshowingthereciprocalrelationshipbetweenthelevelsofDownloadedfromhttp://ahajournals.orgbyonAugust7,2018miR-328andL-typeCa2channelproteinsubunits.2Conclusions—miR-328contributestotheadverseatrialelectricremodelinginAFthroughtargeting
