骨髓源性生长因子

[16]。冠状动脉介入术后再狭窄患者常需接受二次干预治疗，不仅严重影响患者生存质量，亦造成沉重的社会经济负担。阐明再狭窄的分子机制并建立有效的防治策略已成为心血管领域亟待解决的关键科学问题。本研究首次揭示骨髓源性生长因子（MYDGF）对球囊损伤诱导的新生内膜形成具有显著抑制作用，提示该蛋白分子可能为血管再狭窄防治提供新型蛋白质治疗靶点。血管新生内膜形成的关键病理基础在于血管平滑肌细胞（VSMC）的表型转换。合成型VSMC以肌丝含量减少、收缩功能丧失、DNA合成活性降低及细胞外基质生成能力下降为特征REF_Ref32421\r\h[17]。其典型表现为α-平滑肌肌动蛋白（α-SMA）、SM22α等收缩标志物表达下调，同时骨桥蛋白（OPN）表达显著上调REF_Ref32453\r\h[18]。这种表型转换可诱导VSMC发生异常迁移、增殖和细胞外基质分泌，最终导致病理性血管重构REF_Ref32492\r\h[19]。目前临床主要采用药物涂层球囊（DCBs）和药物洗脱支架（DESs）进行干预：DCBs通过球囊扩张实现抗增殖药物的瞬时递送，而DESs则通过持续药物释放抑制新生内膜形成REF_Ref26539\r\h[20]。尽管雷帕霉素及其衍生物仍是当前临床应用的主流药物，但紫杉醇涂层器械引发的晚期动脉血栓风险已引起临床警觉REF_Ref32558\r\h[21]。在此背景下，本研究发现MYDGF对新生内膜形成的抑制作用，为再狭窄防治提供了潜在的新型治疗策略。6、结论本研究证实骨髓源性生长因子MYDGF显著减轻了血管损伤后新生内膜过度增生。这一发现不仅深化了对血管修复机制的理论认知，更为临床防治介入术后再狭窄提供了潜在治疗策略。基于MYDGF开发的靶向干预手段，有望突破传统单一通路疗法的局限性，推动心血管疾病精准治疗体系的革新，具有重要的医学价值。8、参考文献YangX,YangY,GuoJ,MengY,LiM,YangP,etal.Targetingtheepigenomeinin-stentrestenosis:frommechanismstotherapy.MolTherNucleicAcids.2021;23:1136–60.GiacoppoD,AlfonsoF,XuB,ClaessenBEPM,AdriaenssensT,JensenC,etal.Drug-coatedballoonangioplastyversusdrug-elutingstentimplantationinpatientswithcoronarystentrestenosis.JAmCollCardiol.2020;75:2664–78.GiustinoG,ColomboA,CamajA,YasumuraK,MehranR,StoneGW,etal.Coronaryin-stentrestenosis:JACCstate-of-the-artreview.JAmCollCardiol.2022;80:348–72.ZengZ,XiaL,FanS,ZhengJ,QinJ,FanX,etal.CircularRNACircMAP3K5actsasamicroRNA-22-3pspongetopromoteresolutionofintimalhyperplasiaviaTET2-mediatedsmoothmusclecelldifferentiation.Circulation.2021;143:354–71.MelnikT,JordanO,CorpatauxJ-M,DelieF,SaucyF.Pharmacologicalpreventionofintimalhyperplasia:astate-of-the-artreview.PharmacolTher.2022;235:108157.LiuM,GomezD.Smoothmusclecellphenotypicdiversity.ArteriosclerThrombVascBiol.2019;39:1715–23.AshrafJV,AlHajZenA.Roleofvascularsmoothmusclecellphenotypeswitchinginarteriogenesis.IntJMolSci.2021;22:10585.MianoJM,FisherEA,MajeskyMW.Fateandstateofvascularsmoothmusclecellsinatherosclerosis.Circulation.2021;143:2110–6.Korf-KlingebielM,RebollMR,PoltenF,WeberN,JäckleF,WuX,etal.Myeloidderivedgrowthfactorprotectsagainstpressureoverload-inducedheartfailurebypreservingsarco/endoplasmicreticulumCa2+-ATPaseexpressionincardiomyocytes.Circulation.2021;144:1227–40.WangY,LiY,FengJ,LiuW,LiY,LiuJ,etal.Mydgfpromotescardiomyocyteproliferationandneonatalheartregeneration.Theranostics.2020;10:9100–12.CullyM.Cardiovasculardisease:MYDGFpromotesheartrepairaftermyocardialinfarction.NatRevDrugDiscov.2015;14:164–5.HeM,LiY,WangL,GuoB,MeiW,ZhuB,etal.MYDGFattenuatespodocyteinjuryandproteinuriabyactivatingAkt/BADsignalpathwayinmicewithdiabetickidneydisease.Diabetologia.2020;63:1916–31.LiDJ,FuH,TongJ,LiYH,QuLF,WangP,etal.Cholinergicanti-inflammatorypathwayinhibitsneointimalhyperplasiabysuppressinginflammationandoxidativestress.RedoxBiol.2018;15:22–33.MengB,LiY,DingY,XuX,WangL,GuoB,etal.Myeloid-derivedgrowthfactorinhibitsinflammationandalleviatesendothelialinjuryandatherosclerosisinmice.SciAdv.2021;7:eabe6903.XuX,LiY,ShiL,HeK,SunY,DingY,etal.Myeloid-derivedgrowthfactor(MYDGF)protectsbonemassthroughinhibitingosteoclastogenesisandpromotingosteoblastdifferentiation.EMBORep.2022;23:e53509.WilsonS,MoneP,KansakarU,JankauskasSS,DonkorK,AdebayoA,etal.Diabetesandrestenosis.CardiovascDiabetol.2022;21:23.Minai-TehraniA,ChangSH,KwonJT,HwangSK,KimJE,ShinJY,etal.Aerosoldeliveryoflentivirus-mediatedO-glycosylationmutantosteopontinsuppresseslungtumorigenesisinK-ras(LA1)mice.CellOncol.2013;36:15–26.YanC.Cyclicnucleotidephosphodiesterase1andvascularaging.ClinSci.2015;129:1077–81.UllrichH,OlschewskiM,MünzelT,GoriT.Coronaryin-stentrestenosis:predictorsandtreatment.DtschArzteblInt.2021;118:637–44.JegerRV,FarahA,OhlowMA,MangnerN,Möbius-WinklerS,WeilenmannD,etal.Long-termefficacyandsafetyofdrug-coatedballoonsversusdrug-elutingstentsforsmallcoronaryarterydisease(BASKET-SMALL2):3-yearfollow-upofarandomised,non-inferioritytrial.Lancet.2020;396:1504–10.KatsanosK,SpiliopoulosS,KitrouP,KrokidisM,Karnaba