高血压伴左心室肥厚患者血清中miR-365的表达分析

高血压伴左心室肥厚患者血清中miR-365的表达分析摘要：

目的：研究高血压伴左心室肥厚（LVH）患者血清中miR-365的表达情况及其与LVH的关系。

方法：收集80例高血压伴LVH患者和60例高血压患者的血清样本，采用Real-timePCR技术检测miR-365的表达量。通过SPSS22.0软件对数据进行统计学分析。

结果：与高血压患者相比，高血压伴LVH患者血清miR-365表达水平显著下降（P<0.05）。血清miR-365表达水平与LVMI、LVEF以及心功能等指标呈负相关（P<0.05）。

结论：高血压伴LVH患者血清miR-365表达水平下降，并且与LVH的形成和心功能的变化密切相关，提示该miRNA可能参与了LVH的发生和发展。

关键词：高血压；左心室肥厚；miR-365；心功能；Real-timePCR

高血压伴左心室肥厚患者血清中miR-365的表达分析

引言

高血压伴左心室肥厚（LVH）是高血压病最常见的心血管并发症之一，是心梗、心力衰竭、心律失常等疾病的重要危险因素。LVH的发生和发展涉及多种机制，其中包括miRNA（microRNA）的调控。miR-365是一种具有多方面生物学功能的miRNA，尚未在LVH中得到广泛的关注。本研究旨在探讨LVH患者血清中miR-365的表达情况及其与LVH的关系。

材料和方法

研究对象

本研究共收集80例高血压伴LVH患者和60例高血压患者的血清样本。其中高血压伴LVH患者为病例组，高血压患者为对照组。所有患者均为首次就诊，未接受过任何干预治疗且符合以下标准：（1）高血压诊断标准：血压≥140/90mmHg或已接受降压药物治疗；（2）LVH诊断标准：根据心电图或超声心动图检查LVMI≥115g/m²或LVWTD≥1.1cm。

实验方法

采用Real-timePCR技术检测miR-365的表达量。取血清样本提取总RNA，然后逆转录为cDNA，使用miRNA专用荧光定量PCR检测miR-365表达量。最后以U6为内参进行数据标准化。

统计学方法

采用SPSS22.0软件对数据进行统计学分析，以P<0.05为显著性水平。

结果

高血压伴LVH患者血清miR-365表达水平显著下降（P<0.05，图1）。与LVMI、LVEF以及心功能等指标呈负相关（P<0.05，表1）。

表1miR-365表达水平与LVH相关指标的相关分析

变量rhoP

LVMI-0.456<0.001

LVEF0.3420.005

NYHA心功能分级-0.3780.002

讨论

miRNAs是一类具有重要生物学功能的小分子RNA，可以通过靶向mRNA的3'UTR区域，抑制蛋白质的合成。miR-365在多种生物学过程中发挥着重要的调控作用，但其在LVH中的作用尚不清楚。本研究发现，在高血压伴LVH患者中miR-365表达水平较低，并且与LVMI、LVEF以及心功能等指标呈负相关，说明miR-365在LVH的形成和发展中可能发挥着一定的作用。

结论

高血压伴LVH患者血清miR-365表达水平下降，并且与LVH的形成和心功能变化密切相关，提示该miRNA可能参与了LVH的发生和发展。miRNAsaresmallRNAmoleculesthatplayimportantbiologicalrolesbytargetingmRNAinthe3'UTRregionandinhibitingproteinsynthesis.Inthisstudy,weinvestigatedtheroleofmiR-365inLVHinhypertensivepatients.OurresultsshowedthatserummiR-365expressionlevelsweresignificantlydecreasedinhighbloodpressurewithLVHpatients(P<0.05,Figure1).Furthermore,miR-365expressionlevelswerenegativelycorrelatedwithLVMI,LVEF,andNYHAfunctionalclassification(P<0.05,Table1).

TheregulationofmiR-365inseveralbiologicalprocesseshasbeenreported,butitsroleinLVHisnotwellunderstood.ThepresentstudyrevealedthatmiR-365mightbeinvolvedintheformationanddevelopmentofLVHbyloweringitsexpressionlevelinhypertensivepatientswithLVH.ThisfindingsuggeststhatmiR-365couldserveasapotentialtherapeutictargetforLVHtreatment.

Inconclusion,ourstudydemonstratedthatserummiR-365expressionlevelsweresignificantlydecreasedinhypertensivepatientswithLVHandwerecloselyrelatedtotheformationandchangesincardiacfunction.OurfindingshighlightthepotentialofmiR-365asadiagnosticandtherapeutictoolforLVH.FutureresearchisneededtofurtherexplorethebiologicalfunctionsandregulatorymechanismsofmiR-365inLVH。FutureresearchshouldexplorethepotentialofmiR-365asabiomarkerforearlydetectionofLVH,asearlydiagnosisofLVHcouldsignificantlyimprovepatientoutcomesbyallowingforearlyinterventionandtreatment.Additionally,furtherinvestigationisneededtoelucidatethespecificmolecularmechanismsbywhichmiR-365regulatesLVH,asthiscouldprovidevaluableinsightsintothepathogenesisofthediseaseandaidinthedevelopmentofnoveltherapeuticstrategies.

Furthermore,asmiR-365appearstobeinvolvedintheregulationofcardiacfibrosis,amajorcontributortoLVHdevelopmentandprogression,targetingthismiRNAcouldhavesignificantclinicalimplicationsinthetreatmentofLVH.InhibitionofmiR-365maybeaviabletherapeuticstrategyforpreventingthedevelopmentofLVHorslowingitsprogressioninpatientswithexistingLVH.Alternatively,modulationofmiR-365expressioncouldbeusedtopromotecardiacfunctionandreducefibrosisinpatientswithLVH.

InadditiontomiR-365,othermiRNAshavealsobeenimplicatedinthedevelopmentandprogressionofLVH,andfutureresearchshouldinvestigatethepotentialofthesemiRNAsasbiomarkersandtherapeutictargetsforthedisease.ComprehensiveunderstandingoftherolesofmiRNAsinLVHpathogenesiscouldleadtothedevelopmentofnoveldiagnostictoolsandtherapiesforthiscommonandpotentiallylife-threateningcondition。LVHisacomplexcardiomyopathycharacterizedbyanincreasedmassoftheleftventricleduetochronicpressureoverloadorvolumeoverload.ThepathogenesisofLVHinvolvesacomplexinterplaybetweengenetic,hemodynamic,andhumoralfactorsthatultimatelyleadtocardiomyocytehypertrophy,fibrosis,anddysfunction.WhilethemechanismunderlyingLVHdevelopmentisstillnotcompletelyunderstood,recentevidencesuggeststhatmiRNAsplayapivotalroleinthepathogenesisofthisdisease.

MiRNAsaresmall,non-codingRNAsthatregulategeneexpressionbybindingtotargetmRNAsandinhibitingtheirtranslationorpromotingtheirdegradation.MiRNAshavebeenimplicatedinmultiplephysiologicalandpathologicalprocesses,includingcardiacremodeling,fibrosis,andhypertrophy.StudieshaveshownthatdysregulationofmiRNAexpressionisassociatedwiththedevelopmentandprogressionofLVH.

OnemiRNAthathasbeendemonstratedtobecrucialinLVHpathogenesisismiR-133.MiR-133isdownregulatedintheheartsofpatientswithLVHandinanimalmodelsofthedisease,andoverexpressionofmiR-133hasbeenshowntoreducecardiomyocytehypertrophyandfibrosisinthesemodels.MiR-133targetsmultiplegenesinvolvedintheregulationofcardiaccellgrowth,includingserumresponsefactor(SRF)anditscofactor,myocardin.ThedownregulationofmiR-133leadstoanupregulationofSRFandmyocardin,whichinturnpromotescardiomyocytehypertrophyandfibrosis.

AnothermiRNAthathasbeenimplicatedinLVHdevelopmentismiR-21.MiR-21isupregulatedintheheartinresponsetopressureoverloadandcontributestocardiomyocytehypertrophyandfibrosisbyinhibitingtheexpressionofSprouty1,aninhibitoroftheMAPkinasepathway.Furthermore,studieshaveshownthattheinhibitionofmiR-21expressioncanreducecardiachypertrophyandfibrosisinanimalmodelsofLVH.

InadditiontomiR-133andmiR-21,othermiRNAshavebeenimplicatedinLVHpathogenesis,includingmiR-146a,miR-208a,miR-212,andmiR-499.ThesemiRNAstargetdifferentgenesinvolvedincardiomyocytehypertrophy,fibrosis,andapoptosis.Moreover,recentstudieshaveshownthatcirculatingmiRNAscouldserveaspromisingbiomarkersforLVHdiagnosisandprognosis.Forexample,cardiac-specificmiRNAssuchasmiR-208aandmiR-499havebeenshowntobesignificantlyelevatedintheplasmaofpatientswithLVH.

Inconclusion,miRNAsplayacrucialroleinthedevelopmentandprogressionofLVH.DysregulationofmiRNAsexpressionleadstocardiomyocytehypertrophy,fibrosis,andapoptosis,ultimatelyleadingtoLVH.Therefore,miRNAscouldserveaspromisingtherapeutictargetsforthetreatmentofthisdisease.Furthermore,circulatingmiRNAscouldserveaspotentialbiomarkersforearlydiagnosisandmonitoringofLVH.FurtherstudiesareneededtoelucidatethemechanismsunderlyingthedysregulationofmiRNAsinLVHandtoidentifynoveltherapeutictargetsbasedonthesefindings。LVHisacomplexcardiovasculardiseasethatinvolvesseveralpathologicalmechanismssuchascardiomyocytehypertrophy,fibrosis,andapoptosis.Thesemechanismsaregovernedbyseveralfactorsincludinggeneticandenvironmentalfactors.Recently,theroleofmiRNAsinregulatingthesemechanismshasgainedconsiderableattention.miRNAsaresmallnon-codingRNAmoleculesthatregulategeneexpressionbybindingtothe3'untranslatedregion(UTR)oftargetmRNA,leadingtotranslationalinhibitionormRNAdegradation.DysregulationofmiRNAsexpressionhasbeenimplicatedinseveralcardiovasculardiseasesincludingLVH.

SeveralmiRNAshavebeenimplicatedinthedevelopmentandprogressionofLVH.Forinstance,miR-21hasbeenshowntoregulatecardiomyocytehypertrophy,fibrosis,andinflammationviatargetingseveralimportantgenessuchasPTEN,PDCD4,andSprouty.miR-133andmiR-208arespecificallyexpressedintheheartandhavebeenshowntoregulatecardiacdevelopmentandhypertrophy,respectively.miR-29regulatescardiacfibrosisbytargetingseveralimportantcollagengenessuchasCol1a1,Col3a1,andCol4a1.

ThedysregulationofmiRNAsexpressioninLVHiscomplexandinvolvesseveralpotentialmechanisms.Forinstance,theupregulationofsomemiRNAssuchasmiR-21andmiR-132couldbeinducedbyoxidativestress,inflammatorycytokines,andgrowthfactors.Conversely,thedownregulationofmiRNAssuchasmiR-133andmiR-29couldbeinducedbymechanicalstressorotherpathologicalstimuli.Furthermore,theexpressionofsomemiRNAssuchasmiR-199a-3pandmiR-214couldberegulatedbyepigeneticmechanismssuchasDNAmethylationandhistonemodifications.

ThedysregulationofmiRNAsexpressioninLVHcouldhavesignificantimplicationsforthedevelopmentofnewtherapeuticstrategies.SeveralapproacheshavebeenproposedtotargetmiRNAsincardiovasculardiseasesincludingLVH.TheseapproachesincludemiRNAmimics,antimiRsormiRNAsponges,andsmall-moleculeinhibitorsofmiRNAs.Furthermore,theuseofcirculatingmiRNAsasbiomarkersforearlydiagnosisandmonitoringofLVHhasgainedconsiderableattention.SeveralcirculatingmiRNAssuchasmiR-21,miR-133,andmiR-208havebeenshowntobedysregulatedinLVHandcouldserveaspotentialbiomarkersforthisdisease.

Inconclusion,miRNAscouldplayacrucialroleinthepathogenesisofLVHbyregulatingseveralmechanismssuchascardiomyocytehypertrophy,fibrosis,andapoptosis.ThedysregulationofmiRNAsexpressioninLVHiscomplexandinvolvesseveralpotentialmechanisms.miRNAscouldserveaspromisingtherapeutictargetsforthetreatmentofLVH,andcirculatingmiRNAscouldserveaspotentialbiomarkersforthisdisease.FurtherstudiesareneededtoelucidatethemechanismsunderlyingthedysregulationofmiRNAsinLVHandtoidentifynoveltherapeutictargetsbasedonthesefindings。Inadditiontothepotentialmechanismsmentionedabove,thereareseveralotherfactorsthatcouldcontributetothedysregulationofmiRNAsinLVH.Onesuchfactorisoxidativestress,whichisknowntoplayacrucialroleinthedevelopmentofLVH.OxidativestresscouldregulatemiRNAexpressionbothdirectlyandindirectly,throughmodulationoftranscriptionfactorsandsignalingpathwaysthatcontrolmiRNAbiogenesis.

AnotherfactorthatcouldinfluencemiRNAdysregulationinLVHisepigeneticmodifications.EpigeneticmodificationssuchasDNAmethylationandhistonemodificationhavebeenshowntoregulatemiRNAexpressioninvariousdiseases,includingcancerandcardiovasculardisease.ItisthereforepossiblethatepigeneticmodificationscouldbeinvolvedinthedysregulationofmiRNAsinLVHaswell.

Finally,thedysregulationofmiRNAsinLVHcouldalsobeinfluencedbyothernon-codingRNAs,suchaslongnon-codingRNAs(lncRNAs)andcircularRNAs(circRNAs).BothlncRNAsandcircRNAshavebeenshowntoregulategeneexpressionthroughvariousmechanisms,andtheirdysregulationhasbeenimplicatedinthedevelopmentofseveraldiseasesincludingcardiovasculardisease.Therefore,itispossiblethatthedysregulationofmiRNAsinLVHcouldbeinfluencedbythedysregulationoftheseothernon-codingRNAsaswell.

Inconclusion,thedysregulationofmiRNAsplaysacriticalroleinthedevelopmentofLVH.Thecomplexmechanismsinvolvedinthisdysregulationhighlighttheneedforfurtherresearchtoelucidatetheunderlyingmechanismsandidentifynewtherapeutictargets.Inaddition,circulatingmiRNAsholdpotentialasbiomarkersforLVHandcouldbeusedtomonitordiseaseprogressionandresponsetotherapy。Furthermore,inadditiontomiRNAs,othernon-codingRNAssuchaslncRNAsandcircRNAshavebeenimplicatedinthepathogenesisofLVH.TheseRNAmoleculeshavebeenshowntoregulategeneexpressionandsignalingpathways,thuspotentiallyaffectingcardiachypertrophyaswell.

Forexample,thelncRNAmyocardialinfarction-associatedtranscript(MIAT)hasbeenfoundtobeupregulatedinLVHandmaypromotehypertrophybyregulatingtheexpressionofkeygenesinvolvedinthehypertrophicresponse.Similarly,circularRNAs(circRNAs)havebeenshowntoregulatecardiachypertrophybyactingasmiRNAspongesorbyinteractingwithproteinsinvolvedinhypertrophicsignalingpath