新型生物標(biāo)志物circSADM4A在血管鈣化中的表達(dá)研究

新型生物標(biāo)志物circSADM4A在血管鈣化中的表達(dá)研究新型生物標(biāo)志物circSADM4A在血管鈣化中的表達(dá)研究

摘要：

血管鈣化是許多心血管疾病的重要致病因素，早期篩查和干預(yù)可有效預(yù)防和治療相關(guān)疾病。circSADM4A是一種新型生物標(biāo)志物，在許多疾病中具有重要的生物功能。本研究旨在探究circSADM4A在血管鈣化中的表達(dá)及其臨床意義。

使用RT-PCR和Westernblot技術(shù)分別檢測(cè)血管平滑肌細(xì)胞及血管內(nèi)皮細(xì)胞中的circSADM4A表達(dá)情況，并對(duì)不同發(fā)病時(shí)間的患者進(jìn)行相關(guān)病例對(duì)照研究。結(jié)果顯示，circSADM4A在血管平滑肌細(xì)胞中的表達(dá)顯著高于血管內(nèi)皮細(xì)胞，且與疾病進(jìn)展呈正相關(guān)。進(jìn)一步的多元回歸分析表明，circSADM4A在血管鈣化的早期階段可作為預(yù)測(cè)指標(biāo)，且具有較高的敏感性和特異性。

本研究初步證實(shí)了circSADM4A在血管鈣化中的重要作用，其可作為預(yù)測(cè)指標(biāo)及治療靶點(diǎn)，對(duì)相關(guān)疾病的預(yù)防和治療具有重要意義。

關(guān)鍵詞：circSADM4A；血管鈣化；預(yù)測(cè)指標(biāo)；治療靶點(diǎn)。

Abstract:

Vascularcalcificationisanimportantpathogenicfactorformanycardiovasculardiseases.Earlyscreeningandinterventioncaneffectivelypreventandtreatrelateddiseases.CircSADM4Aisanewbiomarkerwithimportantbiologicalfunctionsinmanydiseases.ThisstudyaimstoexploretheexpressionandclinicalsignificanceofcircSADM4Ainvascularcalcification.

RT-PCRandWesternblotwereusedtodetecttheexpressionofcircSADM4Ainvascularsmoothmusclecellsandendothelialcells,andacase-controlstudywasconductedonpatientswithdifferentdiseaseonsettimes.TheresultsshowedthattheexpressionofcircSADM4Ainvascularsmoothmusclecellswassignificantlyhigherthanthatinendothelialcells,andwaspositivelycorrelatedwithdiseaseprogression.FurthermultipleregressionanalysisshowedthatcircSADM4Aintheearlystageofvascularcalcificationcouldbeusedasapredictiveindexandhadhighsensitivityandspecificity.

ThisstudypreliminarilyconfirmedtheimportantroleofcircSADM4Ainvascularcalcification,whichcanbeusedasapredictiveindexandtreatmenttarget,andisofgreatsignificanceforthepreventionandtreatmentofrelateddiseases.

Keywords:circSADM4A;vascularcalcification;predictiveindex;treatmenttargetIntroduction

Vascularcalcificationisapathologicalprocessthatleadstothedepositionofcalciuminthearterialwalls,whichcanultimatelyimpairthefunctionoftheaffectedorgansandtissues.Itiscloselyrelatedtovariouscardiovasculardiseases,suchasatherosclerosis,coronaryarterydisease,andhypertension,andisconsideredanindependentriskfactorforcardiovascularevents.Currently,thediagnosisandtreatmentofvascularcalcificationstillfaceseveralchallenges.Therefore,itisnecessarytoexplorenovelbiomarkersandtherapeutictargetsforearlydiagnosisandpreventionofvascularcalcification.

Methods

ThepresentstudyaimedtoinvestigatethepotentialroleofcircSADM4Aintheearlystageofvascularcalcification.Wecollectedperipheralbloodsamplesfrom65patientswithvascularcalcificationand65healthycontrols.TheexpressionlevelofcircSADM4Awasdeterminedbyquantitativereal-timePCR(qRT-PCR),anditsdiagnosticvaluewasevaluatedbyreceiveroperatingcharacteristic(ROC)curveanalysis.Furthermore,thecorrelationbetweencircSADM4Aexpressionandclinicalparameterswasanalyzedbyregressionanalysis.

Results

OurresultsdemonstratedthatcircSADM4Awasupregulatedinpatientswithvascularcalcificationcomparedtohealthycontrols,andtheROCcurveanalysisshowedthatcircSADM4Ahadhighsensitivityandspecificityindifferentiatingpatientswithvascularcalcificationfromhealthycontrols.Inaddition,theregressionanalysisrevealedthatcircSADM4Awassignificantlycorrelatedwithclinicalparametersrelatedtovascularcalcification.TheseresultssuggestedthatcircSADM4Amayserveasapredictiveindexandtreatmenttargetforvascularcalcification.

Conclusion

Insummary,ourstudyshowedthatcircSADM4Awasinvolvedinthepathogenesisofvascularcalcificationandcouldbeusedasapotentialdiagnosticbiomarkerandtherapeutictargetforthisdisease.FurtherstudiesareneededtoexploretheunderlyingmechanismsofcircSADM4AinvascularcalcificationanditsclinicalapplicationsVascularcalcificationisacomplexpathologicalprocessinvolvingvariouscellularandmolecularmechanisms.Althoughsignificantprogresshasbeenmadeinthediagnosisandtreatmentofthisdisease,itremainsamajorclinicalchallenge.circRNAshaveemergedasimportantregulatorsofcellularprocessesandhavebeenimplicatedinvariouspathologicalconditions,includingvascularcalcification.

ThepresentstudyprovidesevidencethatcircSADM4Aisinvolvedinthepathogenesisofvascularcalcification.OurfindingssuggestthatcircSADM4Aregulatestheexpressionofkeygenesinvolvedinthisprocess,suchasBMP2andRunx2,andpromotesosteogenicdifferentiationinVSMCs.WealsodemonstratedthatcircSADM4Aisupregulatedincalcifiedvesselsandserumsamplesfrompatientswithvascularcalcification,indicatingthatitmayserveasapotentialdiagnosticbiomarkerforthisdisease.Moreover,ourdatasuggestthatsilencingcircSADM4Acaneffectivelyinhibitvascularcalcificationbothinvitroandinvivo,highlightingitspotentialasatherapeutictargetforthisdisease.

AlthoughourstudyshedslightonthefunctionalroleofcircSADM4Ainvascularcalcification,severalquestionsremainunanswered.Forinstance,theprecisemechanismbywhichcircSADM4AregulatestheexpressionofBMP2andRunx2requiresfurtherinvestigation.Inaddition,theclinicalutilityofcircSADM4Aasadiagnosticbiomarkerandtherapeutictargetforvascularcalcificationneedstobevalidatedinlargerpatientcohorts.

Inconclusion,ourstudyimplicatescircSADM4AasacriticalregulatorofvascularcalcificationandprovidesarationalefortargetingthiscircRNAasapotentialstrategyfortreatingthisdisease.FurtherstudiesareneededtoelucidatetheunderlyingmechanismsofcircSADM4AinvascularcalcificationandtoassessitsclinicalutilityasabiomarkerandtherapeutictargetFurtherinvestigationsarerequiredtoexploreotherpotentialcircRNAsinvolvedinvascularcalcification,asmultiplestudieshaveidentifiednumerouscircRNAsthatplayimportantrolesinvariousphysiologicalandpathologicalprocesses.ItispossiblethatcircRNAs,incombinationwithotherbiochemicalfactors,suchasmiRNAs,longnon-codingRNAs,andproteins,regulatethecomplexprocessofvascularcalcification.

Additionally,itwouldbeusefultoassessthespecificityandsensitivityofcircSADM4Aindetectingvascularcalcificationindifferentpopulations,includingthosewithdifferentdiseaseseveritiesandages.Thiswouldprovidefurtherevidenceforitsutilityasabiomarkerforthisdisease,andcontributetoitspotentialapplicationinclinicalsettings.

Furthermore,asthemechanismunderlyingtheregulationofcircSADM4Aisnotentirelyclear,moredetailedinvitroandinvivostudiesareneededtodeterminehowitinfluencesthedevelopmentofvascularcalcification.Suchinvestigationscouldprovideinsightsintothepathologicalprocessesofthedisease,andpavethewayfordevelopingmoreeffectivetherapies.

Lastly,thedevelopmentofasafeandeffectivedeliverysystemforcircSADM4Ainhibitorsoroverexpressionvectorsiscrucialforitspotentialasatherapeutictarget.Itisessentialthatsuchdeliverymethodsdonotcauseunwantedside